bluuebunny/crossref_metadata_2025 huggingface dataset:
Semaglutide as a potential therapeutic alternative for HNF1B-MODY: a case study
Authors: Almutair Angham , Almulhem Beshaier
Published: March 2024

Maturity-onset diabetes of the young (MODY) is a grouping of monogenic disorders. It is characterized by dominantly inherited, non-insulin-dependent diabetes. MODY is relatively rare, encompassing up to 3.5% in those diagnosed under 30 years of age. Specific types are most commonly treated with sulfonylurea, particularly those identified as HNF4A-MODY and HNF1A-MODY. HNF1B-MODY is another type that is most frequently managed with insulin therapy but lacks a defined precision treatment. We present an 18-year-old, non-obese female patient diagnosed with HNF1B-MODY. She displays complete gene deletion, a renal cyst, and hypomagnesemia. Her treatment plan includes both long- and short-acting insulin, though she frequently encountered hypoglycemia and hyperglycemia. Semaglutide, a GLP-1RA, was administered weekly over 4 months. The patient’s glucose level was continuously tracked using Dexcom’s Continuous Glucose Monitoring system. The data suggested a notable improvement in her condition: time-in-range (TIR) increased from 70% to 88%, with some days achieving 100%, and the frequency of hypoglycemic episodes, indicated by time-below-range values, fell from 5% to 1%. The time-above-range values also dropped from 25% to 10%, and her HbA1c levels declined from 7% to 5.6%. During the semaglutide therapy, we were able to discontinue her insulin treatment. Additionally, her body mass index (BMI) was reduced from 24.1 to 20.1 kg/m2. However, the semaglutide treatment was halted after 4 months due to side effects such as nausea, vomiting, and reduced appetite. Other contributing factors included exam stress and a COVID-19 infection, which forced a switch back to insulin. Her last recorded HbA1c level under exclusive insulin therapy rose to 7.1%, and her BMI increased to 24.9 kg/m2. In conclusion, semaglutide could potentially replace insulin to improve glucose variability, TIR, and HbA1c in patients with HNF1B-MODY. However, more extensive studies are required to confirm its long-term safety and efficacy.
Phthalate metabolites and sex steroid hormones in relation to obesity in US adults: NHANES 2013-2016
Authors: Zhang Jiechang , Gu Wen , Zhai Shilei , Liu Yumeng , Yang Chengcheng , Xiao Lishun , Chen Ding
Published: March 2024

Background

Obesity and metabolic syndrome pose significant health challenges in the United States (US), with connections to disruptions in sex hormone regulation. The increasing prevalence of obesity and metabolic syndrome might be associated with exposure to phthalates (PAEs). Further exploration of the impact of PAEs on obesity is crucial, particularly from a sex hormone perspective.

Methods

A total of 7780 adult participants in the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2016 were included in the study. Principal component analysis (PCA) coupled with multinomial logistic regression was employed to elucidate the association between urinary PAEs metabolite concentrations and the likelihood of obesity. Weighted quartiles sum (WQS) regression was utilized to consolidate the impact of mixed PAEs exposure on sex hormone levels (total testosterone (TT), estradiol and sex hormone-binding globulin (SHBG)). We also delved into machine learning models to accurately discern obesity status and identify the key variables contributing most to these models.

Results

Principal Component 1 (PC1), characterized by mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate (MEHHP), and mono(2-ethyl-5-oxohexyl) phthalate (MEOHP) as major contributors, exhibited a negative association with obesity. Conversely, PC2, with monocarboxyononyl phthalate (MCNP), monocarboxyoctyl phthalate (MCOP), and mono(3-carboxypropyl) phthalate (MCPP) as major contributors, showed a positive association with obesity. Mixed exposure to PAEs was associated with decreased TT levels and increased estradiol and SHBG. During the exploration of the interrelations among obesity, sex hormones, and PAEs, models based on Random Forest (RF) and eXtreme Gradient Boosting (XGBoost) algorithms demonstrated the best classification efficacy. In both models, sex hormones exhibited the highest variable importance, and certain phthalate metabolites made significant contributions to the model’s performance.

Conclusions

Individuals with obesity exhibit lower levels of TT and SHBG, accompanied by elevated estradiol levels. Exposure to PAEs disrupts sex hormone levels, contributing to an increased risk of obesity in US adults. In the exploration of the interrelationships among these three factors, the RF and XGBoost algorithm models demonstrated superior performance, with sex hormones displaying higher variable importance.
Adaptive compound power quality disturbance detection via OMD and improved networks for renewable energy systems
Authors: Wu Shuangxi , Liu Yang , Zhu Yu , Xiao Huangqing , Zhang Zhan , Yang Ping
Published: March 2024

In the evolving landscape of power systems, the integration of various renewable energy resources (RERs) introduces complex challenges, particularly in maintaining power quality, which are paramount for system stability. To address this issue, an adaptive power quality disturbance (PQD) detection framework is implemented in this paper. First, the optimal mode decomposition (OMD) is developed to decompose the compound PQDs into sub-ingredients to make them more visible based on the optimal energy ratio. Subsequently, we propose an improved attention convolutional neural network (IACNN), an advanced neural network architecture that leverages an enhanced attention mechanism to expedite the identification of PQDs. Importantly, the sub-ingredients can be strengthened based on the established PQD detection framework. Finally, a series of experiments are conducted under different noise levels and various types of PQDs. The results demonstrate that the proposed framework has profound detection effectivity with about 99.2% accuracy under the simulation condition of 20 dB noise level. In addition, the experimental verification analysis proves a satisfactory real-time performance. This underscores the potential of the proposed framework as a significant advancement in the realm of power quality management, offering a robust solution to the challenges posed by the integration of RERs into modern power systems.
The effect of litter decomposition mostly depends on seasonal variation of ultraviolet radiation rather than species in a hyper-arid desert
Authors: Wang Peng , Liu Yalan , Zhang Bo , Li Lei , Lin Lisha , Li Xiangyi , Zeng Qiang
Published: March 2024

Introduction: Ultraviolet (UV) radiation is believed to play a significant role in accelerating litter decomposition in water-limited ecosystems. Litter traits also influence the decomposition. However, the dominance of litter traits and ultraviolet radiation on litter decomposition in hyper-arid deserts (annual precipitation: potential evaporation < 0.05) with diverse species and seasonal variations remain unclear.

Methods: To address this knowledge gap, we examined the decomposition of three dominant litter species (Karelinia caspia, Alhagi sparsifolia, and Populus euphratica) in the southern edge of the Taklimakan Desert, Northwest China.

Results: Our results revealed that under UV radiation conditions, K. caspia, A. sparsifolia, and P. euphratica experienced mass losses of 45.4%, 39.8%, and 34.9%, respectively, and 20%, 22.2% and 17.4%, respectively under UV filtering treatment. Specifically, the loss rate of carbon and lignin under UV radiation, was 2.5 and 2.2 times higher than under UV filtering treatment, respectively.

Conclusion: UV radiation did not dominate decomposition throughout the year in our study area, and the loss rate of litter traits was significantly higher in summer than in winter under UV radiation. Moreover, this photodegradation is related to the intensity of UV exposure, but not to precipitation or temperature. Surprisingly, species type had no significant effect on litter decomposition. However, when we applied a UV filtering treatment, we observed higher loss rates of nitrogen compared with the ambient treatment, suggesting the involvement of other spectra in the litter decomposition process. Overall, our findings elucidate that UV radiation is a crucial factor that affects litter mass loss. The magnitude of this effect mostly varies with the season rather than the species of litter.
Impact of persistent barrier to gene flow and catastrophic events on red algae evolutionary history along the Chilean coast
Authors: Huanel Oscar R. , Montecinos Alejandro E. , Sepúlveda-Espinoza Francisco , Guillemin Marie-Laure
Published: March 2024

Historical vicariance events, linked to the existence of stable physical barriers to gene flow, generate concordant genetic breaks in co-distributed species while stochastic processes (e.g., costal uplift) could cause species-specific genetic breaks as a result of local strong demographic bottlenecks or extinction. In Chile, previous studies show that the area of the 30°S-33°S could correspond to a stable barrier to gene flow that have affected the genetic structure of various algae and marine invertebrates. Here we sequenced two organellar genes (COI and rbcL) in four taxonomically accepted co-distributed red seaweeds species characterized by a low dispersal potential: Mazzaella laminarioides, M. membranacea, Asterfilopsis disciplinalis, and Ahnfeltiopsis vermicularis. Our results revealed the existence of ten strongly differentiated linages in the taxa studied. Strong genetic breaks, concordant in both space and time (divergence estimated to have occurred some 2.9–12.4 million years ago), were observed between taxa distributed across the 33°S. Conversely, in the Central/South part of the Chilean coast, the localization of the genetic breaks/sub-structure observed varied widely (36°S, 38°S, 39°S, and 40°S). These results suggest that a major historical vicariance event has modeled the genetic structure of several Chilean marine organisms in the north of the Chilean coast during the mid-Miocene, while more recent stochastic events and genetic drift could be the driving forces of genetic divergence/structuration in the central-southern part of the coast.
Revisiting roles of mast cells and neural cells in keloid: exploring their connection to disease activity
Authors: Yeo Eunhye , Shim Joonho , Oh Se Jin , Choi YoungHwan , Noh Hyungrye , Kim Heeyeon , Park Ji-Hye , Lee Kyeong-Tae , Kim Seok-Hyung , Lee Dongyoun , Lee Jong Hee
Published: March 2024

Background

Mast cells (MCs) and neural cells (NCs) are important in a keloid microenvironment. They might contribute to fibrosis and pain sensation within the keloid. However, their involvement in pathological excessive scarring has not been adequately explored.

Objectives

To elucidate roles of MCs and NCs in keloid pathogenesis and their correlation with disease activity.

Methods

Keloid samples from chest and back regions were analyzed. Single-cell RNA sequencing (scRNA-seq) was conducted for six active keloids (AK) samples, four inactive keloids (IK) samples, and three mature scar (MS) samples from patients with keloids.

Results

The scRNA-seq analysis demonstrated notable enrichment of MCs, lymphocytes, and macrophages in AKs, which exhibited continuous growth at the excision site when compared to IK and MS samples (P = 0.042). Expression levels of marker genes associated with activated and degranulated MCs, including FCER1G, BTK, and GATA2, were specifically elevated in keloid lesions. Notably, MCs within AK lesions exhibited elevated expression of genes such as NTRK1, S1PR1, and S1PR2 associated with neuropeptide receptors. Neural progenitor cell and non-myelinating Schwann cell (nmSC) genes were highly expressed in keloids, whereas myelinating Schwann cell (mSC) genes were specific to MS samples.

Conclusions

scRNA-seq analyses of AK, IK, and MS samples unveiled substantial microenvironmental heterogeneity. Such heterogeneity might be linked to disease activity. These findings suggest the potential contribution of MCs and NCs to keloid pathogenesis. Histopathological and molecular features observed in AK and IK samples provide valuable insights into the mechanisms underlying pain and pruritus in keloid lesions.
Case report: A family of atypical hemolytic uremic syndrome involving a CFH::CFHR1 fusion gene and CFHR3-1-4-2 gene duplication
Authors: Tasaki Yuko , Tsujimoto Hiroshi , Yokoyama Tadafumi , Sugimoto Naotoshi , Kitajima Shinji , Fujii Hiroshi , Hidaka Yoshihiko , Kato Noritoshi , Maruyama Shoichi , Inoue Norimitsu , Wada Taizo
Published: March 2024

Mutations in the complement factor H (CFH) gene are associated with complement dysregulation and the development of atypical hemolytic uremic syndrome (aHUS). Several fusion genes that result from genomic structural variation in the CFH and complement factor H-related (CFHR) gene regions have been identified in aHUS. However, one allele has both CFHR gene duplication and CFH::CFHR1 fusion gene have not been reported. An 8-month-old girl (proband) presented with aHUS and was treated with ravulizumab. Her paternal grandfather developed aHUS previously and her paternal great grandmother presented with anti-neutrophil cytoplasmic antibody-associated vasculitis and thrombotic microangiopathy (TMA). However, the proband’s parents have no history of TMA. A genetic analysis revealed the presence of CFH::CFHR1 fusion gene and a CFHR3-1-4-2 gene duplication in the patient, her father, and her paternal grandfather. Although several fusion genes resulting from structural variations of the CFH–CFHR genes region have been identified, this is the first report of the combination of a CFH::CFHR1 fusion gene with CFHR gene duplication. Because the CFH–CFHR region is highly homologous, we hypothesized that CFHR gene duplication occurred. These findings indicate a novel pathogenic genomic structural variation associated with the development of aHUS.
Expression of immune related genes and possible regulatory mechanisms in different stages of non-alcoholic fatty liver disease
Authors: He Risheng , Guan Canghai , Zhao Xudong , Yu Liang , Cui Yunfu
Published: March 2024

Background

Non-alcoholic fatty liver disease (NAFLD), which includes simple steatosis (SS) and non-alcoholic steatohepatitis (NASH), is a significant contributor to liver disease on a global scale. The change of immunity-related genes (IRGs) expression level leads to different immune infiltrations. However, the expression of IRGs and possible regulatory mechanisms involved in NAFLD remain unclear. The objective of our research is to investigate crucial genes linked to the development of NAFLD and the transition from SS to NASH.

Methods

Dataset GSE89632, which includes healthy controls, SS patients, and NASH patients, was obtained using the GEO database. To examine the correlation between sets of genes and clinical characteristics, we employed weighted gene co-expression network analysis (WGCNA) and differential expression analysis. Hub genes were extracted using a network of protein-protein interactions (PPI) and three different machine learning algorithms. To validate the findings, another dataset that is publicly accessible and mice that were subjected to a high-fat diet (HFD) or MCD diet were utilized. Furthermore, the ESTIMATE algorithm and ssGSEA were employed to investigate the immune landscape in the normal versus SS group and SS versus NASH group, additionally, the relationship between immune infiltration and the expression of hub genes was also examined.

Results

A total of 28 immune related key genes were selected. Most of these genes expressed reverse patterns in the initial and progressive stages of NAFLD. GO and KEGG analyses showed that they were focused on the cytokine related pathways and immune cell activation and chemotaxis. After screening by various algorithms, we obtained two hub genes, including JUN and CCL20. Validation of these findings was confirmed by analyzing gene expression patterns in both the validation dataset and the mouse model. Ultimately, two hub genes were discovered to have a significant correlation with the infiltration of immune cells.

Conclusion

We proposed that there were dynamic changes in the expression levels of IRGs in different stages of NAFLD disease, which led to different immune landscapes in SS and NASH. The findings of our research could serve as a guide for the accurate management of various phases of NAFLD.
Neoadjuvant therapy with chemotherapy and immune checkpoint inhibitor for laryngeal function preservation in locally advanced hypopharyngeal cancer
Authors: Wu San-Gang , Wang Run-Jie , Zhou Yi , Luo Xian-Yang
Published: March 2024

Purpose

To evaluate the efficacy and laryngeal function preservation of neoadjuvant treatment with chemotherapy and immune checkpoint inhibitor for locally advanced hypopharyngeal cancer (LAHPC).

Methods

We retrospectively collected LAHPC patients who were diagnosed between February 2022 and June 2023. The patients received a combination of chemotherapy and immune checkpoint inhibitors as the neoadjuvant therapy. The response to treatment, laryngeal function preservation rate, and short-term survival were assessed.

Results

A total of 20 patients were included. Of these patients, 17 (85.0%) had stage IVA-B disease. Ten (50%) and four (20%) patients achieved pathological complete response (PCR) and major pathological response (MPR) to the primary tumor, respectively. In addition, 6 patients had incomplete pathological response (IPR). In the neck, 19 patients had node-positive disease before treatment, and only 5 patients (26.4%) had PCR to regional lymph nodes. Pathologically positive lymph nodes were still observed in 14 (73.6%) patients. Significant downgrading on narrow-band imaging assessment in primary tumors was associated with a higher probability of PCR or MPR than those with IPR (92.9% vs. 33.3%, P=0.014). The overall rate of laryngeal preservation was 95.0%. No severe perioperative complications or perioperative death were found. All patients completed the recommended postoperative radiotherapy/chemoradiotherapy. The median follow-up period was 12.1 months. The 1-year progression-free survival and overall survival were 94.1% and 92.9%, respectively. During the follow-up period, all 19 patients who underwent laryngeal preservation surgery had their laryngeal function preserved.

Conclusion

The addition of an immune checkpoint inhibitor to neoadjuvant chemotherapy effectively preserves laryngeal function without increasing complications related to surgery and postoperative radiotherapy in LAHPC.
Multiple environmental antigens may trigger autoimmunity in psoriasis through T-cell receptor polyspecificity
Authors: Ishimoto Tatsushi , Arakawa Yukiyasu , Vural Secil , Stöhr Julia , Vollmer Sigrid , Galinski Adrian , Siewert Katherina , Rühl Geraldine , Poluektov Yuri , Delcommenne Marc , Horvath Orsolya , He Mengwen , Summer Burkhard , Pohl Ralf , Alharbi Rehab , Dornmair Klaus , Arakawa Akiko , Prinz Jörg C.
Published: March 2024

Introduction

Psoriasis is a T-cell mediated autoimmune skin disease. HLA-C*06:02 is the main psoriasis-specific risk gene. Using a Vα3S1/Vβ13S1 T-cell receptor (TCR) from a lesional psoriatic CD8+ T-cell clone we had discovered that, as an underlying pathomechanism, HLA-C*06:02 mediates an autoimmune response against melanocytes in psoriasis, and we had identified an epitope from ADAMTS-like protein 5 (ADAMTSL5) as a melanocyte autoantigen. The conditions activating the psoriatic autoimmune response in genetically predisposed individuals throughout life remain incompletely understood. Here, we aimed to identify environmental antigens that might trigger autoimmunity in psoriasis because of TCR polyspecificity.

Methods

We screened databases with the peptide recognition motif of the Vα3S1/Vβ13S1 TCR for environmental proteins containing peptides activating this TCR. We investigated the immunogenicity of these peptides for psoriasis patients and healthy controls by lymphocyte stimulation experiments and peptide-loaded HLA-C*06:02 tetramers.

Results

We identified peptides from wheat, Saccharomyces cerevisiae, microbiota, tobacco, and pathogens that activated both the Vα3S1/Vβ13S1 TCR and CD8+ T cells from psoriasis patients. Using fluorescent HLA-C*06:02 tetramers loaded with ADAMTSL5 or wheat peptides, we find that the same CD8+ T cells may recognize both autoantigen and environmental antigens. A wheat-free diet could alleviate psoriasis in several patients.

Discussion

Our results show that due to TCR polyspecificity, several environmental antigens corresponding to previously suspected psoriasis risk conditions converge in the reactivity of a pathogenic psoriatic TCR and might thus be able to stimulate the psoriatic autoimmune response against melanocytes. Avoiding the corresponding environmental risk factors could contribute to the management of psoriasis.
Rapid mangrove expansion triggered by low river discharge episode in Nanliu river estuary, Beibu Gulf of China
Authors: Liu Tao , Huang Rongyong , Sun Yonggen , Liu Ying , Song Zhiguang
Published: March 2024

Mangrove forest is a critical primary producer, biological habitat, and carbon sink in the subtropical-tropical coast zone, and the natural variation of mangrove coverage deserves study for a better understanding of the dynamics of mangrove coastal evolution. In this study, multispectral Landsat images from 1985 to 2018 are used to reconstruct the change in the coverage of mangrove (dominant species is Aegiceras corniculatum) and salt marsh (dominant species is Cyperus malaccensis) in the Nanliu River estuary. Tidal flat elevation measuring and 210Pb dating is used to study the substrate elevation when mangroves first colonize salt marsh. Historical temperature records, river discharge records, and the time series N/P concentration in sediment are analyzed. It is found that the mangrove forests have expanded rapidly in salt marsh since the mid-1980s. The change in factors such as accommodation space, cold event frequency, and nutrient supply cannot explain the origin of mangrove expansion. A low river discharge episode lasting for 8 years since 1986 is considered to have triggered the mangrove expansion in this area, as previously established salt marsh plants died due to germination restriction caused by high salinity and mangroves colonized the salt marsh habitat during this period. This case proves again that estuarine wetlands are very sensitive to salinity variation.
Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis
Authors: Chen Xiao cong , Li Wei ju , Zeng Jia ying , Dong Yun peng , Qiu Jian ming , Zhang Bing , Wang Dong yang , Liu Jun , Lyu Zhao hui
Published: March 2024

Introduction

Postmenopausal osteoporosis (PMOP) is a common chronic disease, and the loss of bone density and bone strength after menopause are its main symptoms. Effective treatments for PMOP are still uncertain, but Chinese medicine has some advantages in slowing down bone loss. Shengu granules are often used clinically to treat PMOP. It has been shown to be an effective prescription for the treatment of PMOP, and there is evidence that gut flora may play an important role. However, whether Shengu granules attenuate PMOP by modulating gut flora and related mechanisms remains unclear.

Methods

In this study, we mainly examined the bone strength of the femur, the structure of the intestinal microbiota, SCFAs in the feces and the level of FOXP3 cells in the colon. To further learn about the inflammation response, the condition of the mucosa and the level of cytokines in the serum also included in the testing. In addition, to get the information of the protein expression, the protein expression of OPG and RANKL in the femur and the protein expression of ZO-1 and Occludin in the colon were taken into account.

Results

The osteoporosis was significantly improved in the SG group compared with the OVX group, and the diversity of intestinal flora, the secretion level of SCFAs and the expression level of FOXP3 were significantly increased compared with the OVX group. In terms of inflammatory indicators, the intestinal inflammation scores of the SG group was significantly lower than those in the OVX group. Additionally, the serum expression levels of IL-10 and TGF-β in the SG group were significantly increased compared with the OVX group, and the expression levels of IL-17 and TNF-α were significantly decreased compared with the OVX group. In terms of protein expression, the expression levels of ZO-1, Occluding and OPG were significantly increased in the SG group compared with the OVX group, and the expression level of RANKL was significantly decreased compared with the OVX group.

Discussion

Shengu granules treatment can improve the imbalance of intestinal flora, increase the secretion of SCFAs and the expression of FOXP3, which reduces the inflammatory response and repairs the intestinal barrier, as well as regulates the expression of OPG/RANKL signaling axis. Overall, Shengu granules ameliorate ovariectomy-induced osteoporosis by the gut-bone-immune axis.
Characterization of ES10 lytic bacteriophage isolated from hospital waste against multidrug-resistant uropathogenic E. coli
Authors: Nawaz Aneela , Zafar Sabeena , Alessa Abdulrahman H. , Khalid Nauman Ahmed , Shahzadi Muqaddas , Majid Alina , Badshah Malik , Shah Aamer Ali , Khan Samiullah
Published: March 2024

Escherichia coli is the major causative agent of urinary tract infections worldwide and the emergence of multi-drug resistant determinants among clinical isolates necessitates the development of novel therapeutic agents. Lytic bacteriophages efficiently kill specific bacteria and seems promising approach in controlling infections caused by multi-drug resistant pathogens. This study aimed the isolation and detailed characterization of lytic bacteriophage designated as ES10 capable of lysing multidrug-resistant uropathogenic E. coli. ES10 had icosahedral head and non-contractile tail and genome size was 48,315 base pairs long encoding 74 proteins. Antibiotics resistance, virulence and lysogenic cycle associated genes were not found in ES10 phage genome. Morphological and whole genome analysis of ES10 phage showed that ES10 is the member of Drexlerviridae. Latent time of ES10 was 30 min, burst size was 90, and optimal multiplicity of infection was 1. ES10 was stable in human blood and subsequently caused 99.34% reduction of host bacteria. Calcium chloride shortened the adsorption time and latency period of ES10 and significantly inhibited biofilm formation of host bacteria. ES10 caused 99.84% reduction of host bacteria from contaminated fomites. ES10 phage possesses potential to be utilized in standard phage therapy.
Effects of dietary chlorogenic acid on cecal microbiota and metabolites in broilers during lipopolysaccharide-induced immune stress
Authors: Hu Xiaodi , Zhen Wenrui , Bai Dongying , Zhong Jiale , Zhang Ruilin , Zhang Haojie , Zhang Yi , Ito Koichi , Zhang Bingkun , Ma Yanbo
Published: March 2024

Aims

The aim of this study was to investigate the effects of chlorogenic acid (CGA) on the intestinal microorganisms and metabolites in broilers during lipopolysaccharide (LPS)-induced immune stress.

Methods

A total of 312 one-day-old Arbor Acres (AA) broilers were randomly allocated to four groups with six replicates per group and 13 broilers per replicate: (1) MS group (injected with saline and fed the basal diet); (2) ML group (injected with 0.5 mg LPS/kg and fed the basal diet); (3) MA group (injected with 0.5 mg LPS/kg and fed the basal diet supplemented with 1,000 mg/kg CGA); and (4) MB group (injected with saline and fed the basal diet supplemented with 1,000 mg/kg CGA).

Results

The results showed that the abundance of beneficial bacteria such as Bacteroidetes in the MB group was significantly higher than that in MS group, while the abundance of pathogenic bacteria such as Streptococcaceae was significantly decreased in the MB group. The addition of CGA significantly inhibited the increase of the abundance of harmful bacteria such as Streptococcaceae, Proteobacteria and Pseudomonas caused by LPS stress. The population of butyric acid-producing bacteria such as Lachnospiraceae and Coprococcus and beneficial bacteria such as Coriobacteriaceae in the MA group increased significantly. Non-targeted metabonomic analysis showed that LPS stress significantly upregulated the 12-keto-tetrahydroleukotriene B4, riboflavin and mannitol. Indole-3-acetate, xanthurenic acid, L-formylkynurenine, pyrrole-2-carboxylic acid and L-glutamic acid were significantly down-regulated, indicating that LPS activated inflammation and oxidation in broilers, resulting in intestinal barrier damage. The addition of CGA to the diet of LPS-stimulated broilers significantly decreased 12-keto-tetrahydro-leukotriene B4 and leukotriene F4 in arachidonic acid metabolism and riboflavin and mannitol in ABC transporters, and significantly increased N-acetyl-L-glutamate 5-semialdehyde in the biosynthesis of amino acids and arginine, The presence of pyrrole-2-carboxylic acid in D-amino acid metabolism and the cecal metabolites, indolelactic acid, xanthurenic acid and L-kynurenine, indicated that CGA could reduce the inflammatory response induced by immune stress, enhance intestinal barrier function, and boost antioxidant capacity.

Conclusion

We conclude that CGA can have a beneficial effect on broilers by positively altering the balance of intestinal microorganisms and their metabolites to inhibit intestinal inflammation and barrier damage caused by immune stress.
Phenolic compounds weaken the impact of drought on soil enzyme activity in global wetlands
Authors: Li Tong , Ge Leming , Zhao Ruotong , Peng Changhui , Zhou Xiaolu , Li Peng , Liu Zelin , Song Hanxiong , Tang Jiayi , Zhang Cicheng , Li Quan , Wang Meng , Zou Ziying
Published: March 2024

Soil enzymes play a central role in carbon and nutrient cycling, and their activities can be affected by drought-induced oxygen exposure. However, a systematic global estimate of enzyme sensitivity to drought in wetlands is still lacking. Through a meta-analysis of 55 studies comprising 761 paired observations, this study found that phosphorus-related enzyme activity increased by 38% as result of drought in wetlands, while the majority of other soil enzyme activities remained stable. The expansion of vascular plants under long-term drought significantly promoted the accumulation of phenolic compounds. Using a 2-week incubation experiment with phenol supplementation, we found that phosphorus-related enzyme could tolerate higher biotoxicity of phenolic compounds than other enzymes. Moreover, a long-term (35 years) drainage experiment in a northern peatland in China confirmed that the increased phenolic concentration in surface layer resulting from a shift in vegetation composition inhibited the increase in enzyme activities caused by rising oxygen availability, except for phosphorus-related enzyme. Overall, these results demonstrate the complex and resilient nature of wetland ecosystems, with soil enzymes showing a high degree of adaptation to drought conditions. These new insights could help evaluate the impact of drought on future wetland ecosystem services and provide a theoretical foundation for the remediation of degraded wetlands.
The effect and mechanism of volatile oil emulsion from leaves of Clausena lansium (Lour.) Skeels on Staphylococcus aureus in vitro
Authors: Guo Yan-Na , He Ke-Ren , Liang Shao-Shan , Mou Rui-Wei , Lu Meng-Han , He Yong-Ming , Tang Lu-Ping
Published: March 2024

This study aimed to develop a suitable dosage form of volatile oil from wampee leaves and to explore its antibacterial mechanism in vitro. The chemical composition of the volatile oil from wampee leaves was determined by gas chromatography-mass spectrometry (GC-MS). Different microemulsion ratios were tested and their stabilities were investigated to determine the optimal ratio. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of the wampee leaves volatile oil emulsion (WVOE) against Salmonella typhimurium (S. typhimurium) and Staphylococcus aureus (S. aureus) were determined using double-dilution and plate-counting methods, respectively. Morphological changes in these two bacteria were observed using scanning electron microscopy. Death, ultrastructural morphology, and biofilm formation were also assessed for S. aureus. Finally, we established an S. aureus-infected Lewis lung carcinoma (LLC) cell model to evaluate the protective effects of the volatile oil emulsion and the associated mechanisms. The volatile oil extracted from wampee leaves contained 37 compounds, of which 96.49% were aromatic hydrocarbons, terpenoids, and their oxygen-containing derivatives. The emulsion was most stable at 1:1 in the oil phase and 1:9 in the water phase. WVOE had poor antibacterial activity against S. typhimurium, but the MIC and MBC against S. aureus were 312.5 and 2,500 μg/mL, respectively. S. aureus survival rates were 84.6%, 14.5%, and 12.8% in the 1/2, 1, and 4 × MIC groups, respectively, compared with 97.2% in the control group. S. typhimurium survival was not affected by WVOE treatment. WVOE administration induced cavity formation and abnormal binary fission, and significantly inhibited biofilm formation in S. aureus cells. The WVOE notably reduced the number of S. aureus and inhibited TLR4, NLRP3, NF-κB, IL-6, IL-18, and TNF-α gene expression in S. aureus-infected LLC cells. The WVOE had a significant inhibitory effect on S. aureus and altered its cell membrane permeability. Moreover, it alleviated inflammation by inhibiting the NF-κB-NLRP3 pathway in S. aureus-infected LLC cells.
Regional covariance of white matter hyperintensity volume patterns associated with hippocampal volume in healthy aging
Authors: Van Etten Emily J. , Bharadwaj Pradyumna K. , Grilli Matthew D. , Raichlen David A. , Hishaw Georg A. , Huentelman Matthew J. , Trouard Theodore P. , Alexander Gene E.
Published: March 2024

Hippocampal volume is particularly sensitive to the accumulation of total brain white matter hyperintensity volume (WMH) in aging, but how the regional distribution of WMH volume differentially impacts the hippocampus has been less studied. In a cohort of 194 healthy older adults ages 50–89, we used a multivariate statistical method, the Scaled Subprofile Model (SSM), to (1) identify patterns of regional WMH differences related to left and right hippocampal volumes, (2) examine associations between the multimodal neuroimaging covariance patterns and demographic characteristics, and (3) investigate the relation of the patterns to subjective and objective memory in healthy aging. We established network covariance patterns of regional WMH volume differences associated with greater left and right hippocampal volumes, which were characterized by reductions in left temporal and right parietal WMH volumes and relative increases in bilateral occipital WMH volumes. Additionally, we observed lower expression of these hippocampal-related regional WMH patterns were significantly associated with increasing age and greater subjective memory complaints, but not objective memory performance in this healthy older adult cohort. Our findings indicate that, in cognitively healthy older adults, left and right hippocampal volume reductions were associated with differences in the regional distribution of WMH volumes, which were exacerbated by advancing age and related to greater subjective memory complaints. Multivariate network analyses, like SSM, may help elucidate important early effects of regional WMH volume on brain and cognitive aging in healthy older adults.
Exploring the application and challenges of fNIRS technology in early detection of Parkinson’s disease
Authors: Hui Pengsheng , Jiang Yu , Wang Jie , Wang Congxiao , Li Yingqi , Fang Boyan , Wang Hujun , Wang Yingpeng , Qie Shuyan
Published: March 2024

Background

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder that significantly benefits from early diagnosis for effective disease management and intervention. Despite advancements in medical technology, there remains a critical gap in the early and non-invasive detection of PD. Current diagnostic methods are often invasive, expensive, or late in identifying the disease, leading to missed opportunities for early intervention.

Objective

The goal of this study is to explore the efficiency and accuracy of combining fNIRS technology with machine learning algorithms in diagnosing early-stage PD patients and to evaluate the feasibility of this approach in clinical practice.

Methods

Using an ETG-4000 type near-infrared brain function imaging instrument, data was collected from 120 PD patients and 60 healthy controls. This cross-sectional study employed a multi-channel mode to monitor cerebral blood oxygen changes. The collected data were processed using a general linear model and β values were extracted. Subsequently, four types of machine learning models were developed for analysis: Support vector machine (SVM), K-nearest neighbors (K-NN), random forest (RF), and logistic regression (LR). Additionally, SHapley Additive exPlanations (SHAP) technology was applied to enhance model interpretability.

Results

The SVM model demonstrated higher accuracy in differentiating between PD patients and control group (accuracy of 85%, f1 score of 0.85, and an area under the ROC curve of 0.95). SHAP analysis identified the four most contributory channels (CH) as CH01, CH04, CH05, and CH08.

Conclusion

The model based on the SVM algorithm exhibited good diagnostic performance in the early detection of PD patients. Future early diagnosis of PD should focus on the Frontopolar Cortex (FPC) region.
Sensorineural correlates of failed functional recovery after natural regeneration of vestibular hair cells in adult mice
Authors: Jáuregui Emmanuel J. , Scheinman Kelli L. , Bibriesca Mejia Ingrid K. , Pruett Lindsay , Zaini Hannah , Finkbeiner Connor , Phillips Jonathan A. , Gantz Jay A. , Nguyen Tot Bui , Phillips James O. , Stone Jennifer S.
Published: March 2024

Vestibular hair cells (HCs) are mechanoreceptors that sense head motions by modulating the firing rate of vestibular ganglion neurons (VGNs), whose central processes project to vestibular nucleus neurons (VNNs) and cerebellar neurons. We explored vestibular function after HC destruction in adult Pou4f3+/DTR (DTR) mice, in which injections of high-dose (50 ng/g) diphtheria toxin (DT) destroyed most vestibular HCs within 2 weeks. At that time, DTR mice had lost the horizontal vestibulo-ocular reflex (aVORH), and their VNNs failed to upregulate nuclear cFos expression in response to a vestibular stimulus (centrifugation). Five months later, 21 and 14% of HCs were regenerated in utricles and horizontal ampullae, respectively. The vast majority of HCs present were type II. This degree of HC regeneration did not restore the aVORH or centrifugation-evoked cFos expression in VNNs. The failure to regain vestibular pathway function was not due to degeneration of VGNs or VNNs because normal neuron numbers were maintained after HC destruction. Furthermore, sinusoidal galvanic stimulation at the mastoid process evoked cFos protein expression in VNNs, indicating that VGNs were able to regulate VNN activity after HC loss. aVORH and cFos responses in VNNs were robust after low-dose (25 ng/g) DT, which compared to high-dose DT resulted in a similar degree of type II HC death and regeneration but spared more type I HCs in both organs. These findings demonstrate that having more type I HCs is correlated with stronger responses to vestibular stimulation and suggest that regenerating type I HCs may improve vestibular function after HC loss.
The effect of argatroban on early neurological deterioration and outcomes in minor ischemic stroke: preliminary findings
Authors: Jin Xuehong , Li Xia , Zhang Hong , Yao Xiaohan , Gu Yongquan , Pei Shaofang , Hu Lan
Published: March 2024

Background

Minor ischemic stroke (MIS) is associated with early neurological deterioration (END) and poor prognosis. Here, we investigated whether argatroban administration can mitigate MIS-associated END and improve functional outcomes by monitoring activated partial thrombin time (APTT).

Methods

Data were collected for patients with MIS admitted to our hospital from January 2019 to December 2022. Patients were divided into a dual antiplatelet therapy (DAPT) group (aspirin + clopidogrel) and an argatroban group (aspirin + argatroban). Those in the latter group who achieved a target APTT of 1.5–3-fold that of baseline and <100 s at 2 h after argatroban infusion were included in the argatroban subgroup. The primary outcome was the END rate of the DAPT group versus that of the argatroban group or the argatroban subgroup. Secondary outcomes included the proportion of patients with modified Rankin Scale (mRS) 0–2 at 7 and 90 days. In addition, baseline date were compared between patients with and without END in the argatroban group.

Results

363 patients were included in the DAPT group and 270 in the argatroban group. There were no significant differences in any above outcome between them. 207 pairs were included in the DAPT group and the argatroban subgroup after 1:1 propensity score matching (PSM). Significant differences were observed in the proportion of END (OR, 2.337; 95% CI, 1.200–4.550, p = 0.011) and mRS 0–2 at 7 days (OR, 0.624; 95% CI, 0.415–0.939, p = 0.023), but not in mRS 0–2 at 90 days or the hemorrhagic events between the two groups. In the argatroban group, univariate analysis showed that the rate of diabetes (OR, 2.316; 95% CI, 1.107–4.482, p = 0.023), initial random blood glucose (OR, 1.235; 95% CI, 1.070–1.425, p = 0.004), drinking history (OR, 0.445; 95% CI, 0.210–0.940, p = 0.031) or those reaching the target APTT (OR, 0.418; 95% CI, 0.184–0.949, p = 0.033) was significantly different among patients with and without END. However, there were no statistical differences in these parameters between them following multivariate analysis.

Conclusion

In patients with MIS, argatroban administration and reaching the target APTT can reduce the incidence of END and improve short-term functional prognosis.
Transcutaneous auricular vagus nerve stimulation with task-oriented training improves upper extremity function in patients with subacute stroke: a randomized clinical trial
Authors: Wang Meng-Huan , Wang Yi-Xiu , Xie Min , Chen Li-Yan , He Meng-Fei , Lin Feng , Jiang Zhong-Li
Published: March 2024

Background

Transcutaneous auricular vagus nerve stimulation (taVNS) has emerged as a promising brain stimulation modality in poststroke upper extremity rehabilitation. Although several studies have examined the safety and reliability of taVNS, the mechanisms underlying motor recovery in stroke patients remain unclear.

Objectives

This study aimed to investigate the effects of taVNS paired with task-oriented training (TOT) on upper extremity function in patients with subacute stroke and explore the potential underlying mechanisms.

Methods

In this double-blinded, randomized, controlled pilot trial, 40 patients with subacute stroke were randomly assigned to two groups: the VNS group (VG), receiving taVNS during TOT, and the Sham group (SG), receiving sham taVNS during TOT. The intervention was delivered 5 days per week for 4 weeks. Upper extremity function was measured using the Fugl-Meyer Assessment-Upper Extremity (FMA-UE), the Action Research Arm Test (ARAT). Activities of daily living were measured by the modified Barthel Index (MBI). Motor-evoked potentials (MEPs) were measured to evaluate cortical excitability. Assessments were administered at baseline and post-intervention. Additionally, the immediate effect of taVNS was detected using functional near-infrared spectroscopy (fNIRS) and heart rate variability (HRV) before intervention.

Results

The VG showed significant improvements in upper extremity function (FMA-UE, ARAT) and activities of daily living (MBI) compared to the SG at post-intervention. Furthermore, the VG demonstrated a higher rate of elicited ipsilesional MEPs and a shorter latency of MEPs in the contralesional M1. In the VG, improvements in FMA-UE were significantly associated with reduced latency of contralesional MEPs. Additionally, fNIRS revealed increased activation in the contralesional prefrontal cortex and ipsilesional sensorimotor cortex in the VG in contrast to the SG. However, no significant between-group differences were found in HRV.

Conclusion

The combination of taVNS with TOT effectively improves upper extremity function in patients with subacute stroke, potentially through modulating the bilateral cortex excitability to facilitate task-specific functional recovery.
Frontline pembrolizumab monotherapy for metastatic non-small cell lung cancer with PD-L1 expression ≥50%: real-world outcomes in a US community oncology setting
Authors: Gadgeel Shirish M. , Rai Pragya , Annavarapu Srinivas , Alam Sartaj , Goldschmidt Jerome H. , West Howard (Jack) , Santorelli Melissa , Martins Renata Eiras
Published: March 2024

Background

This study investigated real-world time on treatment (rwToT) and overall survival (OS) for patients with metastatic non-small cell lung cancer (mNSCLC) who initiated first-line (1L) pembrolizumab monotherapy. We also explored discontinuation reasons and subsequent treatments, stratified by number of cycles among those who completed ≥17 cycles of 1L pembrolizumab.

Methods

Patients with mNSCLC without actionable genetic aberrations, Eastern Cooperative Oncology Group performance status (ECOG PS) 0-2 and unknown, and PD-L1 TPS ≥ 50% starting 1L pembrolizumab monotherapy between 24-Oct-2016 and 31-Dec-2018 within The US Oncology Network were identified retrospectively and evaluated using structured data, with a data cutoff of 30-Sep-2021. Patient characteristics and disposition were summarized using descriptive statistics. OS and rwToT were evaluated using Kaplan-Meier method for all ECOG PS and PS 0-1. A subgroup of patients who completed ≥17 cycles were evaluated using supplemental chart review data to discern reasons for discontinuation.

Results

Of the 505 patients with mNSCLC with PD-L1 TPS ≥50%, 61% had ECOG PS 0-1, 23% had ECOG PS 2, and 65% had nonsquamous histology. Median rwToT and OS of pembrolizumab were 7.0 (95% CI, 6.0–8.4) months and 24.5 (95% CI, 20.1–29.3) months, respectively. In the subgroup with ECOG PS 0-1, they were 7.6 months (95% CI, 6.2-9.2) and 28.8 months (95% CI, 22.4-37.5), respectively. Of the 103 patients who completed ≥17 cycles, 57 (55.3%) patients received 17 – 34 cycles and 46 (44.7%) patients received ≥35 cycles. Approximately 7.7% of the study population received pembrolizumab beyond 35 cycles. Most common reasons for discontinuation were disease progression (38.6%) and toxicity (19.3%) among patients who received 17-34 cycles of pembrolizumab, and disease progression (13.0%) and completion of therapy (10.9%) among patients who received ≥35 cycles.

Conclusion

Consistent with findings from KEYNOTE-024 and other real-world studies, this study demonstrates the long-term effectiveness of pembrolizumab monotherapy as 1L treatment for mNSCLC with PD-L1 TPS ≥50%. Among patients who completed ≥17 cycles, nearly half completed ≥35 cycles. Disease progression and toxicity were the most common reasons for discontinuation among patients who received 17-34 cycles of pembrolizumab. Reasons for discontinuation beyond 35 cycles need further exploration.