bluuebunny/crossref_metadata_2025 huggingface dataset:
The mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors
Authors: Zhan Xiaoyan , Li Qiang , Xu Guang , Xiao Xiaohe , Bai Zhaofang
Published: January 2023

NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3) is a cytosolic pattern recognition receptor (PRR) that recognizes multiple pathogen-associated molecular patterns (PAMPs) and damage-associated molecular patterns (DAMPs). Once activated, NLRP3 initiates the inflammasome assembly together with the adaptor ASC and the effector caspase-1, leading to caspase-1 activation and subsequent cleavage of IL-1β and IL-18. Aberrant NLRP3 inflammasome activation is linked with the pathogenesis of multiple inflammatory diseases, such as cryopyrin­associated periodic syndromes, type 2 diabetes, non-alcoholic steatohepatitis, gout, and neurodegenerative diseases. Thus, NLRP3 is an important therapeutic target, and researchers are putting a lot of effort into developing its inhibitors. The review summarizes the latest advances in the mechanism of NLRP3 inflammasome activation and its pharmacological inhibitors.
Docosahexaenoic acid inhibits TNF-α-induced osteoclast formation and orthodontic tooth movement through GPR120
Authors: Ma Jinghan , Kitaura Hideki , Ogawa Saika , Ohori Fumitoshi , Noguchi Takahiro , Marahleh Aseel , Nara Yasuhiko , Pramusita Adya , Kinjo Ria , Kanou Kayoko , Kishikawa Akiko , Ichimura Atsuhiko , Mizoguchi Itaru
Published: January 2023

Docosahexaenoic acid (DHA) is an omega-3 fatty acid that has a range of positive impacts on human health, including anti-inflammatory effects and inhibition of osteoclast formation via G-protein-coupled receptor 120 (GPR120). Orthodontic force was reported to induce tumor necrosis factor-α (TNF-α) expression, which activates osteoclast differentiation during orthodontic tooth movement (OTM). The aim of this study was to investigate the influence of DHA on TNF-α-induced osteoclast formation and OTM in vivo. We examined osteoclast formation and bone resorption within the calvaria of both wild-type (WT) and GPR120-deficient (GPR120-KO) mice injected with phosphate-buffered saline (PBS), TNF-α, TNF-α and DHA, or DHA. DHA inhibited TNF-α-induced osteoclast formation and bone resorption in WT mice but had no effect in GPR120-KO mice. OTM experiments were performed in mouse strains with or without regular injection of DHA, and the effects of DHA on osteoclast formation in the alveolar bones during OTM were examined. DHA also suppressed OTM in WT but not GPR120-KO mice. Our data showed that DHA suppresses TNF-α-induced osteoclastogenesis and bone resorption via GPR120. TNF-α has considerable significance in OTM, and therefore, DHA may also inhibit TNF-α-induced osteoclast formation and bone resorption in OTM.
Graph coloring-based multichannel MAC protocol in distributed underwater acoustic sensor networks
Authors: Wei Yunlong , Wang Deqing
Published: January 2023

In this paper, the multichannel medium access control (MAC) problem in distributed underwater acoustic sensor networks (UASNs) were investigated. Compared with single-channel MAC protocols in terrestrial radio networks, there exist multichannel hidden terminal problem and long-delay hidden terminal problem in multichannel MAC protocol due to long propagation delay in UASNs. In addition, energy constraint makes channel allocation a challenging problem in distributed UASNs. To solve these aforementioned problems, a new multichannel MAC protocol, called graph coloring-based multichannel MAC protocol (GCMAC) is present. The protocol GCMAC is a synchronized MAC protocol which splits the time into three phases, namely, channel negotiation phase, channel selecting phase and data transmission phase. Specially, the rule for selecting channel is carefully designed based on graph coloring theory to avoid collision and maximize the utilization rate of channels in channel selecting phase. Simulation results show that GCMAC can greatly improve the system throughput and energy efficiency by effectively solving the hidden terminal problems and channel allocation problem.
Single underwater image enhancement based on adaptive correction of channel differential and fusion
Authors: Zhao Zefeng , Zhou Zhuang , Lai Yunting , Wang Tenghui , Zou Shujie , Cai Haohao , Xie Haijun
Published: January 2023

Clear underwater images are necessary in many underwater applications, while absorption, scattering, and different water conditions will lead to blurring and different color deviations. In order to overcome the limitations of the available color correction and deblurring algorithms, this paper proposed a fusion-based image enhancement method for various water areas. We proposed two novel image processing methods, namely, an adaptive channel deblurring method and a color correction method, by limiting the histogram mapping interval. Subsequently, using these two methods, we took two images from a single underwater image as inputs of the fusion framework. Finally, we obtained a satisfactory underwater image. To validate the effectiveness of the experiment, we tested our method using public datasets. The results showed that the proposed method can adaptively correct color casts and significantly enhance the details and quality of attenuated underwater images.
Ocean defenders and human rights
Authors: Bennett Nathan J. , López de la Lama Rocío , Le Billon Philippe , Ertör Irmak , Morgera Elisa
Published: January 2023

Two pressing and overlapping marine policy issues are related to human rights in the ocean and the situation of ocean defenders. Human rights issues and violations are on the rise in the ocean due to the ongoing, rapid and unchecked escalation of anthropogenic activities in marine and coastal environments, which increasingly undermine the fundamental, civil and political, economic, social, cultural or environmental rights of individuals and groups. In this context, it is essential to recognize, support and safeguard the individuals, groups or communities who are mobilizing, advocating or taking action to protect the marine environment, coastal and oceanic territories, and associated human rights from existential threats. Yet, these ‘ocean defenders’ often face marginalization, intimidation, criminalization, threats, violence and murders. The failure to protect the human rights of coastal populations and ocean defenders needs to be urgently rectified by states, the private sector and civil society. We identify six specific areas of urgent action to protect human rights in and related to marine and coastal environments and to support and safeguard ocean defenders.
This is what we know: Assessing the stock status of the data-poor skipjack tuna (Katsuwonus pelamis) fishery in the South China Sea
Authors: Zhang Kui , Zhang Jun , Zhang Peng , Su Li , Hong Xiaofan , Qiu Yongsong , Chen Zuozhi
Published: January 2023

Skipjack tuna (Katsuwonus pelamis) is a highly migratory species of significant value in global marine fisheries. The South China Sea (SCS) is the largest marginal sea in the northwestern Pacific Ocean, and many tuna and tuna-like species occur within it. Although a recent Western and Central Pacific Fisheries Commission report identified skipjack tuna in the western and central Pacific to be sustainably fished, the exploitation status of skipjack tuna in the SCS is still unclear, due to limited data. We apply two data-poor methods, length-based Bayesian biomass estimation (LBB) and length-based spawning potential ratio (LBSPR), to assess the status of skipjack tuna stock in the SCS. We use electronic length frequency analysis to estimate von Bertalanffy growth parameters (asymptotic lengthLinfand growth coefficientK) to serve as priors for LBB and LBSPR estimation. Estimates are calculated for SCS skipjack tunaLinf(68.3 cm),K(0.325 year−1), natural mortality (0.49 year−1) and mean fork length at 50% sexual maturity (36.7 cm). LBB analysis reveals the estimated relative stock size (0.29) indicates that the SCS skipjack tuna stock maybe heavily overfished. LBSPR analysis reveals the estimated spawning potential ratio for this fishery to be 3%, which is significantly below the limit reference point of 20%. Accordingly, for the SCS skipjack tuna stock we identify a need to reduce fishing mortality by controlling fishing effort and increasing catchable size.
Presentation and physical therapy management of upper cervical instability in patients with symptomatic generalized joint hypermobility: International expert consensus recommendations
Authors: Russek Leslie N. , Block Nancy P. , Byrne Elaine , Chalela Susan , Chan Cliffton , Comerford Mark , Frost Nicole , Hennessey Sharon , McCarthy Ann , Nicholson Leslie L. , Parry Jason , Simmonds Jane , Stott Patricia J. , Thomas Lucy , Treleaven Julia , Wagner Wendy , Hakim Alan
Published: January 2023

Experts in symptomatic generalized joint hypermobility (S-GJH) agree that upper cervical instability (UCI) needs to be better recognized in S-GJH, which commonly presents in the clinic as generalized hypermobility spectrum disorder and hypermobile Ehlers-Danlos syndrome. While mild UCI may be common, it can still be impactful; though considerably less common, severe UCI can potentially be debilitating. UCI includes both atlanto-occipital and atlantoaxial instability. In the absence of research or published literature describing validated tests or prediction rules, it is not clear what signs and symptoms are most important for diagnosis of UCI. Similarly, healthcare providers lack agreed-upon ways to screen and classify different types or severity of UCI and how to manage UCI in this population. Consequently, recognition and management of UCI in this population has likely been inconsistent and not based on the knowledge and skills of the most experienced clinicians. The current work represents efforts of an international team of physical/physiotherapy clinicians and a S-GJH expert rheumatologist to develop expert consensus recommendations for screening, assessing, and managing patients with UCI associated with S-GJH. Hopefully these recommendations can improve overall recognition and care for this population by combining expertise from physical/physiotherapy clinicians and researchers spanning three continents. These recommendations may also stimulate more research into recognition and conservative care for this complex condition.
Inflammatory arthritis in systemic sclerosis is associated with elevated C-reactive protein and requires musculoskeletal ultrasound for reliable detection
Authors: Feldmann Daria , Jandova Ilona , Heilmeier Ursula , Kollert Florian , Voll Reinhard E. , Finzel Stephanie
Published: January 2023

Objectives

About 25% of patients with systemic sclerosis (SSc) have elevated C-reactive protein (CRP) levels. Specific causes of CRP elevation are unknown so far. We aimed to investigate whether inflammatory arthritis is associated with CRP elevation. Furthermore, we evaluated the sensitivity and specificity of clinical examination compared to musculoskeletal ultrasound (MSUS) for detection of arthritis.

Methods

Sixty-five patients with SSc (51 females) were enrolled and allocated into a CRP-positive (CRP+,n= 20; CRP elevated for at least two years prior to enrollment) and a CRP-negative (CRP−;n= 45) cohort. All patients were examined clinically (modified Rodnan Skin Score, mRSS; swollen/tender joint count 66/68), received a comprehensive MSUS of their hands and feet, as well as laboratory testing (antibody status; CRP). Statistical analyses were performed using non-parametrical tests without adjustments.

Results

Patient with a disease duration <3 years had higher CRP levels (p= 0.042). Anti-centromere antibodies dominated in CRP- patients (p = 0.013), and anti-Scl70 antibodies in CRP + patients (p= 0.041). Joint effusion and B-mode synovitis prevailed in male (p< 0.00001;p< 0.0001) and CRP + (p= 0.001;p< 0.00001) patients. Power Doppler (PD)-synovitis predominated in patients with diffuse SSc (p= 0.0052). Joint effusion and B-/PD-synovitis were mostly confined to wrists, MTPs and talo-navicular joints. Compared to MSUS, sensitivity of clinical examination was as low as 14.6%; specificity was 87.7%. Sensitivity was reduced by the presence of soft tissue edema or a mRSS > 10.

Conclusion

Arthritis is more frequent in CRP + compared to CRP- SSc patients. Compared to MSUS sensitivity of clinical examination is low for the detection of arthritis; this is likely due to skin fibrosis and soft tissue edema. Therefore, regular monitoring via MSUS should be considered as routine assessment in SSc patients.
Immune infiltration analysis reveals immune cell signatures in salivary gland tissue of primary Sjögren’s syndrome
Authors: Gong Hongxiao , Qiu Xiaoting , Li Pingping , Zhao Runzhi , Wang Beijia , Zhu Ling , Huo Xingxing
Published: January 2023

Introduction

Mouse models are the basis for primary Sjögren’s syndrome (pSS) research. However, the depth of comparisons between mice and humans in salivary gland (SG) immune cells remains limited.

Methods

The gene expression profiles of SGs from normal subjects and pSS patients were downloaded from the Gene Expression Comprehensive Database. The proportion of infiltrating immune cell subsets was then assessed by cell type identification by estimating relative subsets of RNA transcripts (CIBERSORT). An experimental Sjögren’s syndrome (ESS) mouse model was successfully constructed using SG protein. Based on mouse SG tissue RNA-Seq data, the seq-ImmuCC model was used to quantitatively analyze the compositional ratios of 10 immune cells in pSS patients and mouse model SG tissues.

Results

Computed and obtained 31 human data samples using the CIBERSORT deconvolution method. The immune cell infiltration results showed that, compared to normal human SG tissue, the content of gamma delta T cells was significantly different from naive CD4+ T cells and significantly increased, while the plasma cell content decreased. Principal component analysis indicated differences in immune cell infiltration between pSS patients and normal subjects. Meanwhile, for ESS model mouse data analysis, we found that the proportion of macrophages increased, while the proportion of CD4+ T cells, B cells, and monocytes decreased. Furthermore, we found that the proportion of monocytes was decreased, while the proportion of macrophages was increased in the SG tissues of pSS patients and model mice. The infiltration of CD4+ T, CD8+ T, and B cells also showed some differences.

Discussion

We comprehensively analyzed SG immune infiltration in pSS patients and model mice. We demonstrated conserved and nonconserved aspects of the immune system in mice and humans at the level of immune cells to help explain the primary regulation of immune mechanisms during the development of Sjögren’s syndrome.
Anti-microbial, anti-oxidant, and anti-breast cancer properties unraveled in yeast carotenoids produced via cost-effective fermentation technique utilizing waste hydrolysate
Authors: Sinha Sweta , Das Souvik , Saha Biswajit , Paul Debarati , Basu Biswarup
Published: January 2023

Introduction

Natural carotenoids are well known for their anti-oxidant property and also shown to have antimicrobial and anticancer efficacy. Production of carotenoids from microbial resources mainly from yeast has attracted commercial interest. Breast cancer has the highest incidence among women, and therapy resistance and lack of effective therapeutic strategies are major treatment bottlenecks, particularly for triple-negative subtypes. Yeast carotenoids are recently being evaluated for affordable, non-toxic, natural product-based therapies. In the present study, we have shown an environment-friendly and inexpensive method for carotenoid production from yeasts, utilizing “mandi” wastes, and investigated the biomedical properties of carotenoids, particularly antineoplastic properties.

Methods

Vegetable “mandi” waste was used to prepare waste hydrolysate, a culture medium, in which oleaginous red yeast Rhodosporidium sp. was grown. Carotenoid pigments were extracted using the solvent extraction method and analyzed by UV spectroscopy, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC). Antimicrobial, antioxidant, and anticancer activities of the extract were evaluated, followed by in silico docking and absorption, distribution, metabolism, and excretion/toxicity (ADME/T) studies.

Results

Carotenoid extract was found to be composed of three main pigments-β-carotene, torulene, and torularhodin. Extract exhibited significant antioxidant, antimicrobial, and anti-breast cancer activities in vitro while being biocompatible. Interestingly, carotenoids have shown better efficacy in triple-negative breast cancer (TNBC) cells than ER+PR+ cells. In silico evaluation predicted binding with breast cancer-specific molecular targets, specifically the three components showed good binding energy toward VEGF receptors and good drug likeliness properties, as well as less toxicity.

Discussion

This is the first report on anti-breast cancer activities, particularly targeting TNBC cells by red yeast carotenoids (β-carotene, torulene, and torularhodin) produced via a sustainable environment-friendly bioprocess utilizing waste hydrolysate.
Antifungal activity of eco-safe nanoemulsions based on Nigella sativa oil against Penicillium verrucosum infecting maize seeds: Biochemical and physiological traits
Authors: Mosa Mohamed A. , Youssef Khamis , Hamed Said F. , Hashim Ayat F.
Published: January 2023

The main goals of the present investigation were to develop O/W nanoemulsion fungicides based on cold-pressed Nigella sativa (black seed) oil to prevent Penicillium verrucosum infection of maize seeds and to test their antifungal activity against this fungus. Additionally, the effect of these nanoemulsions on plant physiological parameters was also investigated. Two nonionic surfactants namely Tween 20 and Tween 80 were used as emulsifying agents in these formulations. The effect of sonication time and surfactant type on the mean droplet size, polydispersity index (PDI), and zeta potential of the nanoemulsions were determined by dynamic light scattering (DLS). Results indicated that both sonication time and emulsifier type had pronounced effects on the stability of O/W nanoemulsions with a small particle size range (168.6–345.3 nm), acceptable PDI (0.181–0.353), and high zeta potential (−27.24 to –48.82 mV). Tween 20 showed superior stability compared to Tween 80 nanoemulsions. The in vitro results showed that complete inhibition of P. verrucosum-growth was obtained by 10_T80 and 10_T20 nanoemulsions at 100% concentration. All nanoemulsions had increment effects on maize seed germination by 101% in the case of 10_T20 and 10_T80 compared to untreated seeds or the chemical fungicide treatment. Nanoemulsions (10_T20 and 10_T80) were able to stimulate root and shoot length as compared to the fungicide treatment. Seed treatment with 10_T80 nanoemulsion showed the highest AI and protease activity by 75 and 70%, respectively, as compared to the infected control. The produced nanoemulsions might provide an effective protectant coating layer for the stored maize seeds.
Urinary dysfunction in patients with vascular cognitive impairment
Authors: Zhao Panpan , Zhang Guimei , Shen Yanxin , Wang Yongchun , Shi Lin , Wang Zicheng , Wei Chunxiao , Zhai Weijie , Sun Li
Published: January 2023

Vascular cognitive impairment (VCI) is caused by vascular pathologies, with the spectrum of cognitive disorders ranging from subjective cognitive dysfunction to dementia. Particularly among older adults, cognitive impairment is often complicated with urinary dysfunction (UD); some patients may present with UD before cognitive impairment owing to stroke or even when there are white matter hyperintensities on imaging studies. Patients with cognitive impairment often have both language and movement dysfunction, and thus, UD in patients with VCI can often be underdiagnosed and remain untreated. UD has an impact on the quality of life of patients and caregivers, often leading to poor outcomes. Medical history is an important aspect and should be taken from both patients and their caregivers. Clinical assessment including urinalysis, voiding diary, scales on UD and cognitive impairment, post-void residual volume measurement, uroflowmetry, and (video-) urodynamics should be performed according to indication. Although studies on UD with VCI are few, most of them show that an overactive bladder (OAB) is the most common UD type, and urinary incontinence is the most common symptom. Normal urine storage and micturition in a specific environment are complex processes that require a sophisticated neural network. Although there are many studies on the brain–urinary circuit, the specific circuit involving VCI and UD remains unclear. Currently, there is no disease-modifying pharmacological treatment for cognitive impairment, and anti-acetylcholine drugs, which are commonly used to treat OAB, may cause cognitive impairment, leading to a vicious circle. Therefore, it is important to understand the complex interaction between UD and VCI and formulate individualized treatment plans. This review provides an overview of research advances in clinical features, imaging and pathological characteristics, and treatment options of UD in patients with VCI to increase subject awareness, facilitate research, and improve diagnosis and treatment rates.
Concurrent behavioral and electrophysiological longitudinal recordings for in vivo assessment of aging
Authors: Morrone Christopher Daniel , Tsang Arielle A. , Giorshev Sarah M. , Craig Emily E. , Yu Wai Haung
Published: January 2023

Electrophysiological and behavioral alterations, including sleep and cognitive impairments, are critical components of age-related decline and neurodegenerative diseases. In preclinical investigation, many refined techniques are employed to probe these phenotypes, but they are often conducted separately. Herein, we provide a protocol for one-time surgical implantation of EMG wires in the nuchal muscle and a skull-surface EEG headcap in mice, capable of 9-to-12-month recording longevity. All data acquisitions are wireless, making them compatible with simultaneous EEG recording coupled to multiple behavioral tasks, as we demonstrate with locomotion/sleep staging during home-cage video assessments, cognitive testing in the Barnes maze, and sleep disruption. Time-course EEG and EMG data can be accurately mapped to the behavioral phenotype and synchronized with neuronal frequencies for movement and the location to target in the Barnes maze. We discuss critical steps for optimizing headcap surgery and alternative approaches, including increasing the number of EEG channels or utilizing depth electrodes with the system. Combining electrophysiological and behavioral measurements in preclinical models of aging and neurodegeneration has great potential for improving mechanistic and therapeutic assessments and determining early markers of brain disorders.
Predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania: A prospective cohort study
Authors: Matuja Sarah Shali , Mlay Gilbert , Kalokola Fredrick , Ngoya Patrick , Shindika Jemima , Andrew Lilian , Ngimbwa Joshua , Ahmed Rashid Ali , Tumaini Basil , Khanbhai Khuzeima , Mutagaywa Reuben , Manji Mohamed , Sheriff Faheem , Mahawish Karim
Published: January 2023

Background

Stroke is the second leading cause of death worldwide, with the highest mortality rates in low- to middle-income countries, particularly in sub-Saharan Africa. We aimed to investigate the predictors of 30-day mortality among patients with stroke admitted at a tertiary teaching hospital in Northwestern Tanzania.

Methods

This cohort study recruited patients with the World Health Organization's clinical definition of stroke. Data were collected on baseline characteristics, the degree of neurological impairment at admission (measured using the National Institutes of Health Stroke Scale), imaging and electrocardiogram (ECG) findings, and post-stroke complications. The modified Rankin scale (mRS) was used to assess stroke outcomes. Kaplan–Meier analysis was used to describe survival, and the Cox proportional hazards model was used to examine predictors of mortality.

Results

A total of 135 patients were enrolled, with a mean age of 64.5 years. Hypertension was observed in 76%, and 20% were on regular anti-hypertensive medications. The overall 30-day mortality rate was 37%. Comparing patients with hemorrhagic and ischemic stroke, 25% had died by day 5 [25th percentile survival time (in days): 5 (95% CI: 2–14)] versus day 23 [25th percentile survival time (in days): 23 (95% CI: 11–30) (log-rank p < 0.001)], respectively. Aspiration pneumonia was the most common medical complication, occurring in 41.3% of patients. ECG abnormalities were observed in 54.6 and 46.9% of patients with hemorrhagic and ischemic stroke, respectively. The most common patterns were as follows: ST changes 29.6 vs. 30.9%, T-wave inversion 34.1 vs. 38.3%, and U-waves 18.2 vs. 1.2% in hemorrhagic and ischemic stroke, respectively. Independent predictors for case mortality were as follows: mRS score at presentation (4–5) [aHR 5.50 (95% CI: 2.02–15.04)], aspiration pneumonia [aHR 3.69 (95% CI: 1.71–13.69)], ECG abnormalities [aHR 2.28 (95% CI: 1.86–5.86)], and baseline stroke severity [aHR 1.09 (95% CI: 1.02–1.17)].

Conclusion

Stroke is associated with a high 30-day mortality rate in Northwestern Tanzania. Concerted efforts are warranted in managing patients with stroke, with particular attention to individuals with severe strokes, ECG abnormalities, and swallowing difficulties to reduce early morbidity and mortality.
Consciousness: Matter or EMF?
Authors: McFadden Johnjoe
Published: January 2023

Conventional theories of consciousness (ToCs) that assume that the substrate of consciousness is the brain's neuronal matter fail to account for fundamental features of consciousness, such as the binding problem. Field ToC's propose that the substrate of consciousness is the brain's best accounted by some kind of field in the brain. Electromagnetic (EM) ToCs propose that the conscious field is the brain's well-known EM field. EM-ToCs were first proposed only around 20 years ago primarily to account for the experimental discovery that synchronous neuronal firing was the strongest neural correlate of consciousness (NCC). Although EM-ToCs are gaining increasing support, they remain controversial and are often ignored by neurobiologists and philosophers and passed over in most published reviews of consciousness. In this review I examine EM-ToCs against established criteria for distinguishing between ToCs and demonstrate that they outperform all conventional ToCs and provide novel insights into the nature of consciousness as well as a feasible route toward building artificial consciousnesses.
Red-fleshed apple flavonoid extract alleviates CCl4-induced liver injury in mice
Authors: Chen Yizhou , Wang Yanbo , Jiang Shenghui , Xu Jihua , Wang Bin , Sun Xiaohong , Zhang Yugang
Published: January 2023

In recent years, the global incidence of liver damage has increased. Despite the many known health benefits of red-fleshed apple flavonoids, their potential liver-protective effects have not yet been investigated. In this study, we analyzed the composition of red-fleshed apple flavonoid extract (RAFE) by high-performance liquid chromatography (HPLC). We then induced liver damage in mice with carbon tetrachloride (CCl4) and performed interventions with RAFE to analyze its effect on liver damage, using bifendate as a positive control. The results showed that catechin was the most abundant flavonoid in ‘XJ4’ RAFE (49.346 mg/100 g). In liver-injured mice, the liver coefficients converged to normal levels following RAFE intervention. Moreover, RAFE significantly reduced the enzymatic activity levels of glutamic oxaloacetic transaminase (ALT), glutamic alanine transaminase (AST), and alkaline phosphatase (ALP) in mouse serum. Furthermore, RAFE significantly increased the content or enzyme activity level of total glutathione, total antioxidant capacity, and superoxide dismutase, and significantly decreased the content of malondialdehyde in the liver of mice. In parallel, we performed histopathological observations of mouse livers for each group. The results showed that RAFE restored the pathological changes caused by CCl4 around the central hepatic vein in mice and resulted in tightly bound hepatocytes. The recovery effect of RAFE was dose-dependent in the liver tissue. Regarding intestinal microorganisms, we found that RAFE restored the microbial diversity in liver-injured mice, with a similar microbial composition in the RAFE intervention group and normal group. RAFE reduced the ratio of Firmicutes to Bacteroidetes, increased the levels of probiotic bacteria, such as Lactobacillus acidophilus, and Clostridium, and reduced the levels of harmful bacteria, such as Erysipelothrix Rosenbach. Therefore, RAFE ameliorated CCl4-induced liver damage by modulating the abundance and composition of intestinal microorganisms in mice. In conclusion, RAFE alleviated CCl4-induced liver damage in mice, with H-RAFE (5 mg kg–1) significantly improving liver damage in mice but M-RAFE (1 mg kg–1) significantly improving the imbalance of intestinal microorganisms in mice. Our research suggests that RAFE could be employed for the adjuvant treatment and prevention of liver damage, and may have important applications in food and medicine.
Nanomedicines targeting activation of STING to reshape tumor immune microenvironment and enhance immunotherapeutic efficacy
Authors: Chen Shanshan , Peng Anghui , Chen Muhe , Zhan Meixiao
Published: January 2023

Immunotherapy has greatly enhanced the effectiveness of cancer treatments, but the efficacy of many current immunotherapies is still limited by the tumor-suppressive immune microenvironment. Multiple studies have shown that activating the stimulation of IFN genes (STING) pathway and inducing innate immunity can significantly impact the tumor immune microenvironment and improve antitumor therapy. While natural or synthetic STING agonists have been identified or developed for preclinical and clinical use, small molecule agonists have limited utility due to degradation and lack of targeting. As such, the delivery and release of STING agonists into tumor tissue is a major challenge that must be addressed in order to further advance the use of STING agonists. To address this challenge, various nanomedicines have been developed. In this paper, we concisely review the antitumor immunotherapeutic mechanisms of STING agonists, highlighting the latest developments in STING agonists and the current progress of nanomedicines for activating STING. We classify the different nanomedicines according to the STING agonists they utilize in order to facilitate understanding of recent advances in this field. Finally, we also discuss the prospects and challenges of this field.
The role of allogeneic hematopoietic cell transplantation for chronic lymphocytic leukemia: A review
Authors: Puckrin Robert , Shafey Mona , Storek Jan
Published: January 2023

Although the use of allogeneic hematopoietic cell transplantation (HCT) for chronic lymphocytic leukemia (CLL) has declined with the development of novel targeted agents, it continues to play an important role for eligible patients with high-risk or heavily pretreated CLL who lack other treatment options. CLL is susceptible to a potent graft-versus-leukemia (GVL) effect which produces long-lasting remissions in 30-50% of transplanted patients. While allogeneic HCT is associated with significant risks of graft-versus-host disease (GVHD), infection, and non-relapse mortality (NRM), improvements in patient and donor selection, reduced intensity conditioning (RIC), GVHD prophylaxis, and supportive care have rendered this an increasingly safe and effective procedure in the current era. In this review, we discuss recent advances in allogeneic HCT for CLL, with a focus on the optimal evidence-based strategies to maximize benefit and minimize toxicity of this potentially curative cellular therapy.
MRI VS. FDG-PET for diagnosis of response to neoadjuvant therapy in patients with locally advanced rectal cancer
Authors: Gao Peng Fei , Lu Na , Liu Wen
Published: January 2023

Aim

In this study, we aimed to compare the diagnostic values of MRI and FDG-PET for the prediction of the response to neoadjuvant chemoradiotherapy (NACT) of patients with locally advanced Rectal cancer (RC).

Methods

Electronic databases, including PubMed, Embase, and the Cochrane library, were systematically searched through December 2021 for studies that investigated the diagnostic value of MRI and FDG-PET in the prediction of the response of patients with locally advanced RC to NACT. The quality of the included studies was assessed using QUADAS. The pooled sensitivity, specificity, positive and negative likelihood ratio (PLR and NLR), and the area under the ROC (AUC) of MRI and FDG-PET were calculated using a bivariate generalized linear mixed model, random-effects model, and hierarchical regression.

Results

A total number of 74 studies with recruited 4,105 locally advanced RC patients were included in this analysis. The pooled sensitivity, specificity, PLR, NLR, and AUC for MRI were 0.83 (95% CI: 0.77–0.88), 0.85 (95% CI: 0.79–0.89), 5.50 (95% CI: 4.11-7.35), 0.20 (95% CI: 0.14–0.27), and 0.91 (95% CI: 0.88–0.93), respectively. The summary sensitivity, specificity, PLR, NLR and AUC for FDG-PET were 0.81 (95% CI: 0.77-0.85), 0.75 (95% CI: 0.70–0.80), 3.29 (95% CI: 2.64–4.10), 0.25 (95% CI: 0.20–0.31), and 0.85 (95% CI: 0.82–0.88), respectively. Moreover, there were no significant differences between MRI and FDG-PET in sensitivity (P = 0.565), and NLR (P = 0.268), while the specificity (P = 0.006), PLR (P = 0.006), and AUC (P = 0.003) of MRI was higher than FDG-PET.

Conclusions

MRI might superior than FGD-PET for the prediction of the response of patients with locally advanced RC to NACT.
Adult-type rhabdomyoma of the thyroid: A case report
Authors: Jiang ZhenPeng , Zhang MengNi , Huang JiaYan , Song Ling , Lu Qiang
Published: January 2023

Adult-type rhabdomyoma (AR) is a benign myogenous neoplasm. It is rarely located in the thyroid. We present a case of a 61-year-old man, presenting with complaints of a mass found in his left neck for three years. Ultrasonography and computed tomography showed a mass in the left lobe of the thyroid. Subsequently, a fine-needle aspiration biopsy showed that the lesion was suspected to be an oncocytic neoplasm, and the patient underwent surgery. Finally, the lesion was confirmed to be an AR of the thyroid by postoperative pathological diagnosis. In conclusion, AR that occurs in the thyroid is remarkably rare. No case reports to date have described in detail the imaging findings of AR in the thyroid. This study demonstrates the imaging characteristics of a patient with AR of the thyroid, in order to provide more extensive insights to consider the differential diagnosis of thyroid lesions.
Lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy for T4 gastric cancer patients: A retrospective clinical study
Authors: Zhong Yuxin , Kang Wenzhe , Hu Haitao , Li Weikun , Zhang Jing , Tian Yantao
Published: January 2023

Objective

To explore the clinical efficacy of lobaplatin-based prophylactic hyperthermic intraperitoneal chemotherapy (HIPEC) for patients with T4 gastric cancer after surgery and to evaluate its impact on survival.

Materials and methods

Data on patients with T4 gastric cancer who underwent radical gastric resection between March 2016 and August 2017 were collected from the National Cancer Center and Huangxing Cancer Hospital. Enrolled patients were divided into two groups according to receiving or not receiving HIPEC.

Results

A total of 106 patients were included in this study; among them, 51 patients underwent radical gastric resection plus prophylactic HIPEC, and 55 patients underwent radical gastric resection only. The baseline characteristics were well balanced between the two groups. The postoperative platelet counts in the HIPEC group were significantly lower than those in the non-HIPEC group (P < 0.05); however, we did not observe any occurrences of serious bleeding in the HIPEC group. There were no significant differences in the postoperative complication rates between the two groups (P > 0.05). The postoperative (1 month) CEA, CA19-9, and CA72-4 levels in the HIPEC group were significantly decreased in the HIPEC group (P < 0.05). At a median follow-up of 59.3 months, 3 (5.5%) patients in the HIPEC group experienced peritoneal recurrence, and 10 (18.2%) patients in the non-HIPEC group experienced peritoneal recurrence (P < 0.05). Both groups had comparable 5-year overall survival (OS) rates (41.1% HIPEC group vs. 34.5% non-HIPEC group, P = 0.118). The 5-year disease-free survival was significantly higher in the HIPEC group than in the non-HIPEC group (28.6% versus 39.7%, p = 0.046).

Conclusions

Lobaplatin-based prophylactic HIPEC is feasible and safe for patients with T4 gastric cancer and does not increase postoperative adverse effects. The use of HIPEC showed a significant decrease in the incidence of local recurrence rates and blood tumor marker levels. The 5-year disease-free survival was significantly higher in the HIPEC group; however, the 5-year OS benefit was not found in T4 stage patients.
Exploration of sodium homeostasis and pharmacokinetics in bile duct-ligated rats treated by anti-cirrhosis herbal formula plus spironolactone
Authors: Hsueh Tun-Pin , Tsai Tung-Hu
Published: January 2023

Renal sodium retention is an essential indicator that is used for the prognosis of cirrhosis with ascites that requires diuretic treatment to restore sodium homeostasis. The diuretic effects of Yin-Chen-Hao-Tang (YCHT) alone or in combination with diuretics for sodium retention in patients with cirrhosis have not been investigated. This study aimed to investigate the diuretic effects and sodium retention caused by YCHT with spironolactone, from both the pharmacokinetic and pharmacodynamic perspective, in bile duct-ligated rats. The HPLC method was validated and utilized for the pharmacokinetic analysis of rat urine. Urine samples were collected and analyzed every 4 hours for 32 h after oral administration of YCHT at 1 or 3 g/kg daily for 5 days in bile duct-ligated rats. A dose of 20 mg/kg spironolactone was also administered to pretreat the YCHT 1 g/kg or the 3 g/kg group on the 5th day to explore the interaction of the two treatments. Urine sodium, potassium, weight, volume, and spironolactone and canrenone levels were measured to investigate fluid homeostasis after the coadministration. The linearity, precision, and accuracy of the HPLC method were suitable for subsequent urinary pharmacokinetic analyses. The pharmacokinetic parameters in the 1 g/kg YCHT with spironolactone group revealed that the elimination half-life of the spironolactone metabolite, canrenone, was prolonged. In addition, the cumulative excretion amount, the area under the rate curve (AURC), and the maximum rate of excretion (Rmax) were significantly decreased when the spironolactone group was pretreated with 3 g/kg YCHT. Urinary sodium excretion elicited by spironolactone was suppressed by pretreatment with 1 or 3 g/kg YCHT. The 32-hour urine output was not altered by the administration of YCHT alone, but it was significantly decreased by 64.9% after the coadministration of YCHT with spironolactone. The interaction of spironolactone and YCHT was found to decrease urine sodium–potassium and water excretion, and this change was attributed to the decreased level of spironolactone metabolites and possibly the regulation of the renin–angiotensin–aldosterone system by obstructed cirrhosis. The dose adjustment of YCHT or diuresis monitoring should be noted when co-administering YCHT and spironolactone to treat hepatic diseases clinically.
Genetics of spot blotch resistance in bread wheat (Triticum aestivum L.) using five models for GWAS
Authors: Singh Sahadev , Gaurav Shailendra Singh , Vasistha Neeraj Kumar , Kumar Uttam , Joshi Arun Kumar , Mishra Vinod Kumar , Chand Ramesh , Gupta Pushpendra Kumar
Published: January 2023

Genetic architecture of resistance to spot blotch in wheat was examined using a Genome-Wide Association Study (GWAS) involving an association panel comprising 303 diverse genotypes. The association panel was evaluated at two different locations in India including Banaras Hindu University (BHU), Varanasi (Uttar Pradesh), and Borlaug Institute for South Asia (BISA), Pusa, Samastipur (Bihar) for two consecutive years (2017-2018 and 2018-2019), thus making four environments (E1, BHU 2017-18; E2, BHU 2018-19; E3, PUSA, 2017-18; E4, PUSA, 2018-19). The panel was genotyped for 12,196 SNPs based on DArT-seq (outsourced to DArT Ltd by CIMMYT); these SNPs included 5,400 SNPs, which could not be assigned to individual chromosomes and were therefore, described as unassigned by the vendor. Phenotypic data was recorded on the following three disease-related traits: (i) Area Under Disease Progress Curve (AUDPC), (ii) Incubation Period (IP), and (iii) Lesion Number (LN). GWAS was conducted using each of five different models, which included two single-locus models (CMLM and SUPER) and three multi-locus models (MLMM, FarmCPU, and BLINK). This exercise gave 306 MTAs, but only 89 MTAs (33 for AUDPC, 30 for IP and 26 for LN) including a solitary MTA detected using all the five models and 88 identified using four of the five models (barring SUPER) were considered to be important. These were used for further analysis, which included identification of candidate genes (CGs) and their annotation. A majority of these MTAs were novel. Only 70 of the 89 MTAs were assigned to individual chromosomes; the remaining 19 MTAs belonged to unassigned SNPs, for which chromosomes were not known. Seven MTAs were selected on the basis of minimum P value, number of models, number of environments and location on chromosomes with respect to QTLs reported earlier. These 7 MTAs, which included five main effect MTAs and two for epistatic interactions, were considered to be important for marker-assisted selection (MAS). The present study thus improved our understanding of the genetics of resistance against spot blotch in wheat and provided seven MTAs, which may be used for MAS after due validation.
Carotenoid metabolism: New insights and synthetic approaches
Authors: Stra Alice , Almarwaey Lamyaa O. , Alagoz Yagiz , Moreno Juan C. , Al-Babili Salim
Published: January 2023

Carotenoids are well-known isoprenoid pigments naturally produced by plants, algae, photosynthetic bacteria as well as by several heterotrophic microorganisms. In plants, they are synthesized in plastids where they play essential roles in light-harvesting and in protecting the photosynthetic apparatus from reactive oxygen species (ROS). Carotenoids are also precursors of bioactive metabolites called apocarotenoids, including vitamin A and the phytohormones abscisic acid (ABA) and strigolactones (SLs). Genetic engineering of carotenogenesis made possible the enhancement of the nutritional value of many crops. New metabolic engineering approaches have recently been developed to modulate carotenoid content, including the employment of CRISPR technologies for single-base editing and the integration of exogenous genes into specific “safe harbors” in the genome. In addition, recent studies revealed the option of synthetic conversion of leaf chloroplasts into chromoplasts, thus increasing carotenoid storage capacity and boosting the nutritional value of green plant tissues. Moreover, transient gene expression through viral vectors allowed the accumulation of carotenoids outside the plastid. Furthermore, the utilization of engineered microorganisms allowed efficient mass production of carotenoids, making it convenient for industrial practices. Interestingly, manipulation of carotenoid biosynthesis can also influence plant architecture, and positively impact growth and yield, making it an important target for crop improvements beyond biofortification. Here, we briefly describe carotenoid biosynthesis and highlight the latest advances and discoveries related to synthetic carotenoid metabolism in plants and microorganisms.
Soil application of effective microorganisms and nitrogen alleviates salt stress in hot pepper (Capsicum annum L.) plants
Authors: Abdelkhalik Abdelsattar , Abd El-Mageed Taia A. , Mohamed Ibrahim A. A. , Semida Wael M. , Al-Elwany Omar A. A. I. , Ibrahim Ibrahim M. , Hemida Khaulood A. , El-Saadony Mohamed T. , AbuQamar Synan F. , El-Tarabily Khaled A. , Gyushi Mohammed A. H.
Published: January 2023

The application of effective microorganisms (EMs) and/or nitrogen (N) have a stimulating effect on plants against abiotic stress conditions. The aim of the present study was to determine the impact of the co-application of EMs and N on growth, physio-biochemical attributes, anatomical structures, nutrients acquisition, capsaicin, protein, and osmoprotectant contents, as well as the antioxidative defense system of hot pepper (Capsicum annumL.) plants. In the field trials, EMs were not applied (EMs-) or applied (EMs+) along with three N rates of 120, 150, and 180 kg unit N ha-1(designated as N120, N150, and N180, respectively) to hot pepper plants grown in saline soils (9.6 dS m-1). The application of EMs and/or high N levels attenuated the salt-induced damages to hot pepper growth and yield. The application of EMs+with either N150or N180increased the number, average weight and yield of fruits by 14.4 or 17.0%, 20.8 or 20.8% and 28.4 or 27.5%, respectively, compared to hot pepper plants treated with the recommended dose (EMs-× N150). When EMs+was individually applied or combined with either N150or N180, increased accumulation of capsaicin were observed by 16.7 or 20.8%, protein by 12.5 or 16.7%, proline by 19.0 or 14.3%, and total soluble sugars by 3.7 or 7.4%, respectively, in comparison with those treated with the integrative EMs-× N150. In addition, the non-enzymatic contents (ascorbate, and glutathione) and enzymatic activities (catalase, superoxide dismutase, and glutathione reductase) of the antioxidant defense systems significantly increased in hot pepper plants treated with EMs+alone or combined with N150or N180under salt stress conditions. Higher accumulation of nutrients (N, P, K+, and Ca2+) along with reduced Na+acquisition was also evidenced in response to EMs+or/and high N levels. Most anatomical features of stems and leaves recovered in hot pepper plants grown in saline soils and supplied with EMs+and N. The application of EMs and N is undoubtedly opening new sustainable approaches toward enhancing abiotic stress tolerance in crops (e.g. hot pepper).
Interaction between bacterial endophytes and host plants
Authors: Mushtaq Sehrish , Shafiq Muhammad , Tariq Muhammad Rizwan , Sami Adnan , Nawaz-ul-Rehman Muhammad Shah , Bhatti Muhammad Hamza Tariq , Haider Muhammad Saleem , Sadiq Saleha , Abbas Muhammad Taqqi , Hussain Mujahid , Shahid Muhammad Adnan
Published: January 2023

Endophytic bacteria are mainly present in the plant’s root systems. Endophytic bacteria improve plant health and are sometimes necessary to fight against adverse conditions. There is an increasing trend for the use of bacterial endophytes as bio-fertilizers. However, new challenges are also arising regarding the management of these newly discovered bacterial endophytes. Plant growth-promoting bacterial endophytes exist in a wide host range as part of their microbiome, and are proven to exhibit positive effects on plant growth. Endophytic bacterial communities within plant hosts are dynamic and affected by abiotic/biotic factors such as soil conditions, geographical distribution, climate, plant species, and plant-microbe interaction at a large scale. Therefore, there is a need to evaluate the mechanism of bacterial endophytes’ interaction with plants under field conditions before their application. Bacterial endophytes have both beneficial and harmful impacts on plants but the exact mechanism of interaction is poorly understood. A basic approach to exploit the potential genetic elements involved in an endophytic lifestyle is to compare the genomes of rhizospheric plant growth-promoting bacteria with endophytic bacteria. In this mini-review, we will be focused to characterize the genetic diversity and dynamics of endophyte interaction in different host plants.