bluuebunny/crossref_metadata_2025 huggingface dataset:
Early processes in heme-based CO-sensing proteins
Authors: Vos Marten H. , Salman Mayla , Liebl Ursula
Published: November 2022

Carbon monoxide has been recognized relatively recently as signaling molecule, and only very few dedicated natural CO sensor proteins have been identified so far. These include in particular heme-based transcription factors: the bacterial sensor proteins CooA and RcoM. In these 6-coordinated systems, exchange between an internal protein residue and CO as a heme ligand in the sensor domain affects the properties of the DNA-binding domain. Using light to dissociate heme-ligand bonds can in principle initiate this switching process. We review the efforts to use this method to investigate early processes in ligand switching and signaling, with an emphasis on the CO-“trappingˮ properties of the heme cavity. These features are unusual for most heme proteins, but common for heme-based CO sensors.
Drug discovery by a basic research scientist
Authors: Eaton William A.
Published: November 2022

I was fortunate to do my military service during the Vietnam era as a medical officer at the National Institutes of Health (NIH) in Bethesda, Maryland. My first research at NIH was concerned with making a variety of optical measurements on nucleic acid bases and proteins, including single crystal spectra in linearly polarized light and near infrared circular dichroism, interpreting the spectra using molecular orbital and crystal field theories. What I do now is drug discovery, a field at the opposite end of the scientific spectrum. This article gives a brief account of my transition from spectroscopy to sickle cell hemoglobin polymerization to protein folding to drug discovery for treating sickle cell disease. My lab recently developed a high throughput assay to screen the 12,657 compounds of the California Institute of Biomedical Research ReFrame drug repurposing library. This is a precious library because the compounds have either been FDA approved or have been tested in clinical trials. Since the 1970s numerous agents have been reported in the literature to inhibit HbS polymerization and/or sickling with only one successful drug, hydroxyurea, and another of dubious value, voxelotor, even though it has been approved by the FDA. Our screen has discovered 106 anti-sickling agents in the ReFrame compound library. We estimate that as many as 21 of these compounds could become oral drugs for treating sickle cell disease because they inhibit at concentrations typical of the free concentrations of oral drugs in human serum.
Six month lower-leg mechanical tactile sensory stimulation alters functional network connectivity associated with improved gait in older adults with peripheral neuropathy – A pilot study
Authors: Hsu Chun Liang , Manor Brad , Iloputaife Ikechkwu , Oddsson Lars I. E. , Lipsitz Lewis
Published: November 2022

Foot sole somatosensory impairment associated with peripheral neuropathy (PN) is prevalent and a strong independent risk factor for gait disturbance and falls in older adults. Walkasins, a lower-limb sensory prosthesis, has been shown to improve gait and mobility in people with PN by providing afferent input related to foot sole pressure distributions via lower-leg mechanical tactile stimulation. Given that gait and mobility are regulated by sensorimotor and cognitive brain networks, it is plausible improvements in gait and mobility from wearing the Walkasins may be associated with elicited neuroplastic changes in the brain. As such, this study aimed to examine changes in brain network connectivity after 26 weeks of daily use of the prosthesis among individuals with diagnosed PN and balance problems. In this exploratory investigation, assessments of participant characteristics, Functional Gait Assessment (FGA), and resting-state functional magnetic resonance imaging were completed at study baseline and 26 weeks follow-up. We found that among those who have completed the study (N = 8; mean age 73.7 years) we observed a five-point improvement in FGA performance as well as significant changes in network connectivity over the 26 weeks that were correlated with improved FGA performance. Specifically, greater improvement in FGA score over 26 weeks was associated with increased connectivity within the Default Mode Network (DMN; p < 0.01), the Somatosensory Network (SMN; p < 0.01), and the Frontoparietal Network (FPN; p < 0.01). FGA improvement was also correlated with increased connectivity between the DMN and the FPN (p < 0.01), and decreased connectivity between the SMN and both the FPN (p < 0.01) and cerebellum (p < 0.01). These findings suggest that 26 weeks of daily use of the Walkasins device may provide beneficial neural modulatory changes in brain network connectivity via the sensory replacement stimulation that are relevant to gait improvements among older adults with PN.
Flow diversion treatment for giant intracranial serpentine aneurysms
Authors: Tong Xin , He Zijun , Han Mingyang , Feng Xin , Duan Chuanzhi , Liu Aihua
Published: November 2022

Background

Giant serpentine aneurysms (GSAs) are among the most complex and challenging type of intracranial aneurysms. Surgical clipping, bypass, or endovascular parent artery occlusion has been the main treatment of GSAs in the past. However, studies on flow diversion (FD) are limited. Therefore, we reported our experience with patients with GSAs treated with FD.

Methods

Patients with GSAs treated with FD from 2012 to 2020 in our single center were retrospectively reviewed. Angiographic outcomes were graded according to the O’Kelly–Marotta scale as complete occlusion (D), trace filling (C), entry remnant (B), or aneurysm filling (A). Clinical outcomes were assessed using the modified Rankin scale (mRS) score. We also collected the patients’ treatment details and perioperative complications.

Results

Thirteen patients with 14 aneurysms were included, including three in the anterior circulation and 11 in the posterior circulation. Grades B–D were found in 72.7% (8/11) of the GSAs. Good prognosis (mRS score, 0–2) was found in 66.7% (8/12) and 50.0% (6/12) of the patients at the 6-month and latest follow-up, respectively. Parent artery occlusion was found in three cases of GSAs. Five postoperative complications were observed, including two minor complications and three major complications.

Conclusion

Although reconstructive treatment with FD could be considered as one of the treatment strategies for patients with both anterior and posterior circulation GSAs, however, the risk of complications and parent artery occlusion should be considered.
Glutamate receptor-interacting protein 1 in D1- and D2-dopamine receptor-expressing medium spiny neurons differentially regulates cocaine acquisition, reinstatement, and associated spine plasticity
Authors: Chen He , Chen Limei , Yuan Zhirong , Yuan Jiajie , Li Yitong , Xu Yuesi , Wu Jieyi , Zhang Lu , Wang Guohua , Li Juan
Published: November 2022

Background

The nucleus accumbens (NAc) is involved in the expression of cocaine addictive phenotypes, including acquisition, extinction, and reinstatement. In the NAc, D1-medium spiny neurons (MSNs) encode cocaine reward, whereas D2-MSNs encode aversive responses in drug addiction. Glutamate receptor-interacting protein 1 (GRIP1) is known to be associated with cocaine addiction, but the role of GRIP1 in D1-MSNs and D2-MSNs of the NAc in cocaine acquisition and reinstatement remains unknown.

Methods

A conditioned place preference apparatus was used to establish cocaine acquisition, extinction, and reinstatement in mouse models. GRIP1 expression was evaluated using Western blotting. Furthermore, GRIP1-siRNA and GRIP1 overexpression lentivirus were used to interfere with GRIP1 in the NAc. After the behavioral test, green fluorescent protein immunostaining of brain slices was used to detect spine density.

Results

GRIP1 expression decreased during cocaine acquisition and reinstatement. GRIP1-siRNA enhanced cocaine-induced CPP behavior in acquisition and reinstatement and regulated associated spine plasticity. Importantly, the decreased GRIP1 expression that mediated cocaine acquisition and reinstatement was mainly driven by the interference of the GRIP1-GluA2 interaction in D1-MSNs and could be blocked by the interference of the GRIP1-GluA2 interaction in D2-MSNs. Interference with the GRIP1-GluA2 interaction in D1- and D2-MSNs decreased spine density in D1- and D2-MSNs, respectively.

Conclusion

GRIP1 in D1- and D2-MSNs of the NAc differentially modulates cocaine acquisition and reinstatement. GRIP1 downregulation in D1-MSNs has a positive effect on cocaine acquisition and reinstatement, while GRIP1 downregulation in D2-MSNs has a negative effect. Additionally, GRIP1 downregulation in D1-MSNs plays a leading role in cocaine acquisition and reinstatement.
Current state of research on acupuncture for the treatment of amyotrophic lateral sclerosis: A scoping review
Authors: Peng Siyang , Tian Yukun , Chang Weiqian , Yang Yajing , Li Shaohong , Ni Jinxia , Zhu Wenzeng
Published: November 2022

Objective

To provide an overview of the range and characteristics of existing evidence, research gaps, and future research priorities in treating amyotrophic lateral sclerosis (ALS) with acupuncture.

Method

Clinical studies on acupuncture treatment for ALS were searched in 9 databases and two websites. Two independent researchers screened the literature according to the inclusion and exclusion criteria; extracted the demographic data, interventions, and significant findings of the studies; and comprehensively analyzed the characteristics and limitations of the included articles.

Results

A total of 2,326 studies were retrieved, of which 92 were included. Most of the studies were conducted in China, with the number increasing over time. Study designs included case reports, case series, randomized controlled trials (RCTs), and before-and-after studies, among which case reports were the most frequently used. A total of 1,388 patients were enrolled, of whom 1,031 had ALS, 274 had progressive bulbar palsy (PBP), 60 had progressive muscle atrophy (PMA), and 23 had primary lateral sclerosis (PLS). Acupuncture interventions included body acupuncture, electroacupuncture, acupoint injection, scalp acupuncture, acupoint massage, Sa-am acupuncture, needle-embedding therapy, auricular acupuncture, venom pharmacopuncture therapy, plum blossom needling, acupoint paste, electroacupuncture, and needle warming through moxibustion. The most frequently used acupoints were ST36, LI4, SP6, and LI11. Acupuncture is often applied in combination with other treatments, such as herbal or Western medicine. The frequency of treatment ranged from once a month to three times a day, and the duration of treatment ranged from 5 days to 3 years. Clinical symptoms, muscle strength, and effective rates were the most frequently used outcomes. Most studies reported significant efficacy, and only a few studies reported adverse events explicitly.

Conclusion

Evidence gaps include poor study design, complex interventions, limited significance of the selected outcomes, and limited study reporting. The promotion of acupuncture treatment for ALS still faces several obstacles. Rigorous study design and conduct, standardized intervention and outcome measurements, and normative reporting are needed to investigate the efficacy and safety of acupuncture treatment for ALS.
Laryngopharyngeal reflux as a potential cause of Eustachian tube dysfunction in patients with otitis media with effusion
Authors: Zhen Zhen , Zhao Tingting , Wang Quangui , Zhang Junbo , Zhong Zhen
Published: November 2022

Objective

To explore the association between laryngopharyngeal reflux disease (LPRD)-related symptoms and the Eustachian tube (ET) function in adult patients with otitis media with effusion (OME).

Materials and methods

A total of 105 adult patients with OME were retrospectively studied. All these patients had undergone tubomanometry (TMM) test for the affected ears before treatments. The LPRD-related symptoms were all assessed by the Reflux Symptom Index (RSI) scale.

Results

Among the 105 included patients, the numbers of subjects with only one and both two ears affected were 65 (57.1%) and 40 (42.9%), respectively. Therefore, a total of 145 affected ears were studied. For these affected ears, a linear regression analysis that included sex, age, BMI, smoking history, drinking history, RSI value, and the condition of the contralateral ear suggested that only RSI value was significantly associated with TMM value (P < 0.001), with the correlation coefficient of −0.112. Among the 9 symptoms in RSI scale, affected ears with the following symptoms (vs. affected ears without) showed significantly lower TMM values: excess throat mucus or postnasal drip, difficulty swallowing food, liquids, or pills, and sensations of something stuck in your throat or a lump in your throat (all P < 0.05).

Conclusion

LPRD may disrupt ET function in adult OME patients. A higher RSI score is independently predictive for a bad ET patency in such patients and is indicative for an additional anti-reflux therapy.
Structuring and validating a prognostic model for low-grade gliomas based on the genes for plasma membrane tension
Authors: Li Jia , Lv Fangfang , Jin Ting
Published: November 2022

Background

Recent studies indicate that cell mechanics are associated with malignancy through its impact on cell migration and adhesion. Gliomas are the most common primary malignant brain tumors. Low-grade gliomas (LGGs) include diffuse LGGs (WHO grade II) and intermediate-grade gliomas (WHO grade III). Few studies have focused on membrane tension in LGGs. Herein, we assessed the prognostic value of plasma membrane tension-related genes (MTRGs) in LGGs.

Methods

We selected plasma MTRGs identified in previous studies for analysis. Based on LGG RNA sequencing (RNA-seq) data in The Cancer Genome Atlas, a prognostic signature containing four genes was constructed via log-rank testing, LASSO regression and stepwise multivariate Cox regression and was validated with other datasets. Additionally, functional annotation, pathway enrichment and immune and molecular characteristics of the prognostic model defined subgroups were analyzed. Thereafter, a predictive nomogram that integrated baseline characteristics was constructed to determine the 3, 5, and 10-year overall survival (OS) of patients with LGG. Differentially expressed genes were confirmed via quantitative reverse-transcription polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC).

Results

Our MTRG prognostic signature was based on ARFIP2, PICK1, SH3GL2, and SRGAP3 expression levels. The high-risk group was more positively associated with apoptosis and cell adhesion pathways and exhibited a low IDH1 mutation rate, high TP53 mutation rate and a low 1p19q co-deletion rate. The high-risk group also exhibited incremental infiltration of immune cells, more forceful immune activities and high expression of immune checkpoints as well as benefited less from immune therapy compared with the low-risk group. Our prognostic model had better forecasting ability than other scoring systems. We found that the nomogram was a better tool for predicting outcomes for patients with LGG. Finally, qRT-PCR confirmed that SH3GL2 and SRGAP3 expression levels in glioma tissues were significantly lower than those in normal brain tissues. The results of IHC analysis confirmed that SH3GL2 protein expression was higher in patients with longer survival.

Conclusion

Our plasma membrane tension-related gene prognostic signature is a prospective tool that can differentiate between prognosis, gene mutation landscape, immune microenvironment, immune infiltration and immunotherapeutic efficacy in LGG.
Ultrasonic washing as an abiotic elicitor to induce the accumulation of phenolics of fresh-cut red cabbages: Effects on storage quality and microbial safety
Authors: Hong Chen , Zhou Hong-Chang , Zhao Yi-Ming , Ma Haile
Published: November 2022

Ultrasonic washing has been proved to be an abiotic elicitor to induce the accumulation of phenolics in some fruit and vegetables. However, the feasibility of ultrasonic washing on the accumulation of phenolics in fresh-cut red cabbages has not yet been reported. Therefore, the effects of ultrasonic washing on the phenolics and related phenolic metabolism enzymes of fresh-cut red cabbages, as well as quality and microbial safety during cold storage, were investigated. Firstly, the single-factor tests were used to optimize the ultrasonic processing parameters, including frequency mode, frequency amplitude, power density, frequency cycle time, and ultrasonic washing. Then the activities of the enzymes related to phenolic metabolisms after optimal ultrasound treatment were investigated, including phenylalanine ammonia-lyase (PAL), polyphenol oxidase (PPO), and peroxidase (POD). Additionally, the quality and microbial safety of fresh-cut red cabbages stored at 4°C under the optimal ultrasound treatment were evaluated. The results showed that the content of soluble phenolics (SPs) in fresh-cut red cabbages increased significantly during storage under the optimal conditions (28 ± 2 kHz, 60 W/L, 400 ms, and 20 min) compared with the control (P < 0.05). The PAL activity was activated and the PPO and POD activities were inhibited after ultrasonic washing, which contributed to the increase in the content of SPs. Meanwhile, the storage quality and microbial safety of fresh-cut red cabbages were improved. Ultrasonic washing reduced the weight loss and respiration rate and improved the color and texture characteristics. Additionally, the fresh-cut red cabbages after ultrasonic washing showed more retention of ascorbic acid (AA), total soluble proteins (TSPs), total soluble sugars (TSSs), and total soluble solids (SSs) compared with the control. Finally, ultrasonic washing effectively inhibited the growth of bacteria, molds and yeasts, which is beneficial to the extension of the shelf-life of fresh-cut red cabbages. Therefore, ultrasonic washing can be used as a tool to increase the content of SPs in fresh-cut red cabbages while retaining quality attributes and microbial safety.
An insight into bisphenol A, food exposure and its adverse effects on health: A review
Authors: Manzoor Muhammad Faisal , Tariq Tayyaba , Fatima Birjees , Sahar Amna , Tariq Farwa , Munir Seemal , Khan Sipper , Nawaz Ranjha Muhammad Modassar Ali , Sameen Aysha , Zeng Xin-An , Ibrahim Salam A.
Published: November 2022

Bisphenol A (BPA) is a synthetic chemical widely employed to synthesize epoxy resins, polymer materials, and polycarbonate plastics. BPA is abundant in the environment, i.e., in food containers, water bottles, thermal papers, toys, medical devices, etc., and is incorporated into soil/water through leaching. Being a potent endocrine disrupter, and has the potential to alter several body mechanisms. Studies confirmed its anti-androgen action and estrogen-like effects, which impart many negative health impacts, especially on the immune system, neuroendocrine process, and reproductive mechanism. Moreover, it can also induce mutagenesis and carcinogenesis, as per recent scientific research. This review focuses on BPA’s presence and concentrations in different environments, food sources and the basic mechanisms of BPA-induced toxicity and health disruptions. It is a unique review of its type because it focuses on the association of cancer, hormonal disruption, immunosuppression, and infertility with BPA. These issues are widespread today, and BPA significantly contributes to their incidence because of its wide usage in daily life utensils and other accessories. The review also discusses researched-based measures to cope with the toxic chemical.
Novel kinome profiling technology reveals drug treatment is patient and 2D/3D model dependent in glioblastoma
Authors: Fabro Federica , Kannegieter Nynke M. , de Graaf Erik L. , Queiroz Karla , Lamfers Martine L. M. , Ressa Anna , Leenstra Sieger
Published: November 2022

Glioblastoma is the deadliest brain cancer. One of the main reasons for poor outcome resides in therapy resistance, which adds additional challenges in finding an effective treatment. Small protein kinase inhibitors are molecules that have become widely studied for cancer treatments, including glioblastoma. However, none of these drugs have demonstrated a therapeutic activity or brought more benefit compared to the current standard procedure in clinical trials. Hence, understanding the reasons of the limited efficacy and drug resistance is valuable to develop more effective strategies toward the future. To gain novel insights into the method of action and drug resistance in glioblastoma, we established in parallel two patient-derived glioblastoma 2D and 3D organotypic multicellular spheroids models, and exposed them to a prolonged treatment of three weeks with temozolomide or either the two small protein kinase inhibitors enzastaurin and imatinib. We coupled the phenotypic evidence of cytotoxicity, proliferation, and migration to a novel kinase activity profiling platform (QuantaKinome™) that measured the activities of the intracellular network of kinases affected by the drug treatments. The results revealed a heterogeneous inter-patient phenotypic and molecular response to the different drugs. In general, small differences in kinase activation were observed, suggesting an intrinsic low influence of the drugs to the fundamental cellular processes like proliferation and migration. The pathway analysis indicated that many of the endogenously detected kinases were associated with the ErbB signaling pathway. We showed the intertumoral variability in drug responses, both in terms of efficacy and resistance, indicating the importance of pursuing a more personalized approach. In addition, we observed the influence derived from the application of 2D or 3D models in in vitro studies of kinases involved in the ErbB signaling pathway. We identified in one 3D sample a new resistance mechanism derived from imatinib treatment that results in a more invasive behavior. The present study applied a new approach to detect unique and specific drug effects associated with pathways in in vitro screening of compounds, to foster future drug development strategies for clinical research in glioblastoma.
The Global research of protein post-translational modifications in the cancer field: A bibliometric and visualized study
Authors: Ma Ruixia , Zhang Meigui , Xi Jiahui , Li Jing , Ma Yinxia , Han Binxiao , Che Tuanjie , Ma Zhihui , Tian Jinhui , Bai Zhongtian
Published: November 2022

Objectives

Protein post-translational modifications (PTMs) are closely associated with tumorigenesis, targeting PTMs of key proteins might be the focus of antitumor drug discovery. This study aimed to analyze the research progress on protein PTMs in tumorigenesis by performing qualitative and quantitative evaluations.

Methods

The Web of Science Core Collection was selected as the database, and Science Citation Index Expanded was selected as the citation index. Visualization tools such as VOSviewer, CiteSpace, HistCite, and Online Analysis Platform of Bibliometrics were used to deeply explore the information of the retrieved research papers and analyze them in terms of research trends and main aspects of research.

Results

The search yielded 3777 relevant articles. The results showed that the total number of PTMs related papers in cancer field has been increasing annually, with the largest number of papers published in the United States of America. The co-word cluster analysis showed that the research on PTMs and tumorigenesis was primarily focused on the following four areas, mechanism, histone, P53, key Technologies. Tumor metabolism, autophagy, and protein-protein interaction, histone ubiquitination have become new research topics.

Conclusion

This study provides an important reference for the research direction and selection of topics of interest in the PTMs of cancer field.
Pediatric bronchogenic cysts in the head and neck region: A study of 10 surgical cases and a review of the literature
Authors: Chen Wei , Xu MengRou , Wang Qingyu , Xu Hongming , Chen Jiarui , Li Xiaoyan
Published: November 2022

Objective

To explore the clinical characteristics and surgical treatment of children with bronchogenic cysts (BCs) in the head and neck region.

Methods

A retrospective study of 10 pediatric patients with BCs in the head and neck region treated in Shanghai Children's Hospital during 2011 to 2022 was performed.

Results

Based on their pathological diagnosis, 10 patients with BCs in the head and neck were identified. The most common location was the neck (8 patients, 80%; 2 midline neck, 6 lateral neck), followed by the ventral tip of tongue (1 patient), and the posterior pharyngeal wall (1 patient). Misdiagnosed as lymphangioma in 5 cases, cyst in 3 cases, thyroglossal duct cyst (TGDC) in 2 cases and congenital pyriform sinus fistula (CPSF) in 1 case preoperative. The median follow-up period after surgery was 4.68 (range, 0.67–9.25) years. All 10 patients underwent complete resection without recurrence or other complications.

Conclusions

Although extremely rare, BCs should be considered in the differential diagnosis of midline and lateral neck masses or intraoral cysts in children. Surgical excision is recommended in BCs, and the diagnosis is definitively confirmed by histopathology.
Long term NIV in an infant with Hallermann-Streiff syndrome: A case report and overview of respiratory morbidity
Authors: Guerin S , Blanchon S , de Halleux Q , Bayon V , Ferry T
Published: November 2022

Hallermann-Streiff syndrome (HSS) is a rare congenital syndrome with different anomalies including midface hypoplasia, beak nose and micrognathia. The upper airways narrowness can lead to severe respiratory complications such as obstructive sleep apnoea syndrome (OSAS), particularly in infancy. The management of these severe OSAS is difficult and poorly documented in literature. We report the case of an infant with HSS complicated by severe and early OSAS successfully managed with non-invasive ventilation (NIV), provide an overview of respiratory morbidities and discuss treatment options for HSS-related OSAS.
Norcantharidin ameliorates estrogen deficient-mediated bone loss by attenuating the activation of extracellular signal-regulated kinase/ROS/NLRP3 inflammasome signaling
Authors: Yang Guang , Xu Huikang , Yao Minjun , Yan Shigui , Wu Mengrui , Zhou Chenhe
Published: November 2022

Osteoporosis, characterized by reduced bone mass, aberrant bone architecture, and elevated bone fragility, is driven by a disruption of bone homeostasis between bone resorption and bone formation. However, up to now, no drugs are perfect for osteoporosis treatment due to different defects. In this study, we demonstrated that norcantharidin (NCTD) could inhibit osteoclast formation and bone resorption by attenuating the ERK, ROS and NLRP3 inflammasomes pathways in vitro. Moreover, our in vivo study further confirms its preventive effects on estrogen-deficiency bone loss by inhibiting osteoclast formation and functions. Therefore, we could conclude that NCTD might be a potential candidates for the prevention and treatment of osteoporosis.
Danlu tongdu tablets: Preclinical safety evaluation and mechanism of hepatotoxicity
Authors: Zhang Haijing , Yang Yifei , Guo Feifei , He Rong , Gao Shuangrong , Cao Chunyu , Zhao Chunhui , Xia Bing , Xu Qihua , Gong Ping , Wang Lifang , Su Ping , Liu Ting
Published: November 2022

Danlu tongdu tablets (DLTD) is a listed Chinese patent medicine collected in the Pharmacopoeia of the People’s Republic of China (version 2020). This prescription has been applied in clinics in China for lumbar spinal stenosis and lumbosacral disc herniations. The wide application of Danlu tongdu in therapy has raised some clinical adverse reactions, such as significant elevation of alanine transaminase (ALT) and aspartate transaminase (AST) in individual patients after use. The present study aimed to investigate the safety of Danlu tongdu and analyze its adverse effects on the liver. The maximum feasible dose (MFD) was used to carry out the acute toxicity tests. Mortality, adverse effects, body weight and food consumption were recorded for up to 14 days post treatment. In the 6-month chronic toxicity test, sprague-dawley rats were randomly divided into four groups according body weight, the experimental groups were administrated to rats at the concentrations of 1.67, 3.34 and 6.67 g/kg/day, whereas the control group was received the ultrapure water (vehicle) only, 10 ml/kg, once a day. The animal’s body weight, food consumption was monitored weekly. In addition, their hematological and biochemical parameters, body and organ weights and histopathology, were all measured at specific observation time points. Additionally, we further explored the adverse effects mechanism of Danlu tongdu on the liver through transcriptome analysis. No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 1.67 g/kg and 3.34 g/kg, respectively. We found that mild hypertrophy and hyperplasia of hepatic interlobular bile ducts were detected in some rats with doses of 6.67 g/kg after repeated oral administration of Danlu tongdu for 13 and 26 weeks, but the above changes in liver were reversible. The results of transcriptome sequencing showed that Danlu tongdu had a significant effect on cytochrome P450 enzymes in rat liver, especially cytochrome P450 1 (CYP1) subtype. Therefore, the toxic target organ of Danlu tongdu is the liver and the mechanism of mild liver injury is closely related to the up-regulation of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression.
Cpd-42 protects against calcium oxalate nephrocalcinosis-induced renal injury and inflammation by targeting RIPK3-mediated necroptosis
Authors: Hou Bingbing , Liu Mingming , Chen Yang , Ni Weijian , Suo Xiaoguo , Xu Yuexian , He Qiushi , Meng Xiaoming , Hao Zongyao
Published: November 2022

Calcium oxalate (CaOx) crystals, as the predominant component of human kidney stones, can trigger excessive cell death and inflammation of renal tubular epithelial cells, involved in the pathogenesis of nephrocalcinosis. Necroptosis mediated by receptor-interacting protein kinase 3 (RIPK3) serves a critical role in the cytotoxicity of CaOx crystals. Here, we assessed the therapeutic potential of a novel RIPK3 inhibitor, compound 42 (Cpd-42), for CaOx nephrocalcinosis by comparison with dabrafenib, a classic RIPK3 inhibitor. Our results demonstrated that Cpd-42 pretreatment attenuated CaOx crystals-induced renal tubular epithelial cell (TEC) injury by inhibiting necroptosis and inflammation in vitro and in vivo. Furthermore, in an established mouse model of CaOx nephrocalcinosis, Cpd-42 also reduced renal injury while improving the impaired kidney function and intrarenal crystal deposition. Consistent with this finding, Cpd-42 was confirmed to exhibit superior inhibition of necroptosis and protection against renal TEC injury compared to the classic RIPK3 inhibitor dabrafenib in vitro and in vivo. Mechanistically, RIPK3 knockout (KO) tubular epithelial cells pretreated with Cpd-42 did not show further enhancement of the protective effect on crystals-induced cell injury and inflammation. We confirmed that Cpd-42 exerted protective effects by specifically targeting and inhibiting RIPK3-mediated necroptosis to block the formation of the RIPK1-RIPK3 necrosome. Taken together, targeted inhibition of RIPK3-mediated necroptosis with Cpd-42 may provide a potential therapeutic approach for CaOx nephrocalcinosis.
Inflammatory pathophysiological mechanisms implicated in postpartum depression
Authors: Zhu Jialei , Jin Jing , Tang Jing
Published: November 2022

Postpartum Depression (PPD) is a serious psychiatric disorder of women within the first year after delivery. It grievously damages women’s physical and mental health. Inflammatory reaction theory is well-established in depression, and also has been reported associated with PPD. This review summarized the inflammatory pathophysiological mechanisms implicated in PPD, including decreased T cell activation, increased proinflammatory cytokines secretion, active kynurenine pathway, and initiated NLRP3 inflammasome. Clinical and preclinical research are both gathered. Potential therapeutical alternatives targeting the inflammatory mechanisms of PPD were introduced. In addition, this review briefly discussed the differences of inflammatory mechanisms between PPD and depression. The research of inflammation in PPD is limited and seems just embarking, which indicates the direction we can further study. As a variety of risky factors contribute to PPD collectively, therapy for women with PPD should be comprehensive, and clinical heterogeneity should be taken into consideration. As PPD has a predictability, early clinical screening and interventions are also needed. This review aims to help readers better understand the inflammatory pathological mechanisms in PPD, so as to identify biomarkers and potential therapeutic targets in the future.
A classification method for multi-class skin damage images combining quantum computing and Inception-ResNet-V1
Authors: Li Ziyi , Chen Zhengquan , Che Xuanxuan , Wu Yaguang , Huang Dong , Ma Hongyang , Dong Yumin
Published: November 2022

Melanoma is a high-grade malignant tumor. Melanoma and mole lesions are highly similar and have a very high mortality rate. Early diagnosis and treatment have an important impact on the patient’s condition. The results of dermoscopy are usually judged visually by doctors through long-term clinical experience, and the diagnostic results may be different under different visual conditions. Computer-aided examinations can help doctors improve efficiency and diagnostic accuracy. The purpose of this paper is to use an improved quantum Inception-ResNet-V1 model to classify multiple types of skin lesion images and improve the accuracy of melanoma identification. In this study, the FC layer of Inception-ResNet-V1 is removed, the average pooling layer is the last, SVM is used as the classifier, and the convolutional layer is quantized. The performance of the model was tested experimentally on the ISIC 2019 dataset. To prevent the imbalance of the sample data set from affecting the experiment, the sample data is sampled with weight. Experiments show that the method used shows excellent performance, and the classification accuracy rate reaches 98%, which provides effective help for the clinical diagnosis of melanoma.
Differences in pain, disability, and psychological function in low back pain patients with and without anxiety
Authors: Jiang Ying , Wang Yizu , Wang Rui , Zhang Xiaogang , Wang Xueqiang
Published: November 2022

Objectives: Non-specific low back pain affects people of all ages and is a leading contributor to disease burden worldwide. Chronic low back pain (LBP) reduces working hours, increases comorbidities, and increases rehabilitation needs. The aim of this study was to evaluate whether there were differences in pain, dysfunction, and psychological factors between two groups. The supplementary demonstrated the relationship between these influencing factors and anxiety.

Methods: A cross-sectional study was designed to analyze the differences in pain, disability, and psychological function in non-specific LBP patients with and without anxiety. In total, 60 subjects were divided into two groups based on self-rated anxiety scores: 30 patients with SAS score ≥50 were in the low back pain with anxiety group, and 30 for the LBP without anxiety group with SAS score <50. The pain intensity was assessed using the Visual Analog Scale; psychological function, using the Pain Anxiety Symptoms Scale, the Tampa Scale for Kinesiophobia, and the Fear Avoidance Beliefs Questionnaire; functional disability, using the Oswestry Disability Index and the Roland–Morris Disability Questionnaire; quality of life using 36-Item Short-Form Health Survey questionnaire; and the quality of sleep using Pittsburgh Sleep Quality Index, and the relationships between variables and anxiety scores were estimated using Spearman correlation analysis.

Results: A total of 60 participants were enrolled after self-rated anxiety was assessed and the full investigation was finished. The analyses showed significant differences of pain intensity (p = 0.034, disability (ODI, p = 0.007; RMDQ, p = 0.012) and psychological function (TSK, p = 0.000; PASS, p = 0.009; FABQ, p = 0.000; SF-36, p = 0.000; and PSQI, p = 0.000) between the two groups. Spearman correlation analysis showed that the anxiety score had significant positive correlations with functional disability (ODI, p = 0.004 and 95% CI = 0.112–0.573; RMDQ, p = 0.003, 95% CI = 0.135–0.586) and psychological function (TSK, p = 0.001, 95% CI = 0.174–0.612), excellent positive correlation with quality of sleep (PASS, p = 0.025, 95% CI = 0.031–0.512), and strongly negative correlations with the quality of life (SF-36, p = 0.000, 95% CI = 0.761–0.433).

Conclusion: We recognized that anxiety in low back pain patients was mainly due to interaction with the intensity of pain, disability level, and a mass of psychological function. The future research direction could be to alleviate the anxiety on the comprehensive efficacy of patients with low back pain.
Identification and comprehensive analysis of MIPSs in Rosaceae and their expression under abiotic stresses in rose (Rosa chinensis)
Authors: Gangwar Himanshi , Kumari Priya , Gahlaut Vijay , Kumar Sanjay , Jaiswal Vandana
Published: November 2022

The Myo-Inositol-1-phosphate synthase (MIPS) gene family is involved in the myo-inositol synthesis and plays a significant role in signal transduction, membrane biogenesis, oligosaccharides synthesis, auxin storage and transport, programmed cell death and abiotic stress tolerance in plants. This study comprehensively identified the MIPS genes in Rosaceae plant species, and 51 MIPS genes were identified from 26 Rosaceae species. The phylogenetic analysis divided the MIPSs into two clades (clade I; subfamily Amygdaloideae specific, and clade II; subfamily Rosoideae specific). MIPS genes of all 26 Rosaceae species consist of similar gene structure, motif and domain composition, which shows their conserved nature. The cis-regulatory elements (CREs) analysis revealed that most Rosaceae MIPS genes play a role in growth, development, and stress responses. Furthermore, the qRT-PCR analysis also revealed the involvement of RcMIPS gene in plant development and response to abiotic stresses, including drought and heat. The results of the present study contribute to the understanding of the biological function of Rosaceae MIPS genes, and that could be used in further functional validations.
Better tolerance to Huanglongbing is conferred by tetraploid Swingle citrumelo rootstock and is influenced by the ploidy of the scion
Authors: Sivager Gary , Calvez Leny , Bruyere Saturnin , Boisne-Noc Rosiane , Hufnagel Barbara , Cebrian-Torrejon Gerardo , Doménech-Carbó Antonio , Gros Olivier , Ollitrault Patrick , Morillon Raphaël
Published: November 2022

Huanglongbing (HLB) is a disease that is responsible for the death of millions of trees worldwide. The bacterial causal agent belongs to Candidatus Liberibacter spp., which is transmitted by psyllids. The bacterium lead most of the time to a reaction of the tree associated with callose synthesis at the phloem sieve plate. Thus, the obstruction of pores providing connections between adjacent sieve elements will limit the symplastic transport of the sugars and starches synthesized through photosynthesis. In the present article, we investigated the impact of the use of tetraploid Swingle citrumelo (Citrus paradisi Macfrad × Poncirus trifoliata [L.] Raf) rootstock on HLB tolerance, compared to its respective diploid. HLB-infected diploid and tetraploid rootstocks were investigated when grafted with Mexican and Persian limes. Secondary roots were anatomically studied using scanning electron microscopy (SEM) and transmission electron microscopy (TEM) to observe callose deposition at the phloem sieve plate and to evaluate the impact of the bacterium’s presence at the cellular level. Voltammetry of immobilized microparticles (VIMP) in roots was applied to determine the oxidative stress status of root samples. In the field, Mexican and Persian lime leaves of trees grafted onto tetraploid rootstock presented less symptoms of HLB. Anatomical analysis showed much stronger secondary root degradation in diploid rootstock, compared to tetraploid rootstock. Analysis of the root sieve plate in control root samples showed that pores were approximately 1.8-fold larger in tetraploid Swingle citrumelo than in its respective diploid. SEM analyses of root samples did not reveal any callose deposition into pores of diploid and tetraploid genotypes. VIMP showed limited oxidative stress in tetraploid samples, compared to diploid ones. These results were even strongly enhanced when rootstocks were grafted with Persian limes, compared to Mexican limes, which was corroborated by stronger polyphenol contents. TEM analysis showed that the bacteria was present in both ploidy root samples with no major impacts detected on cell walls or cell structures. These results reveal that tetraploid Swingle citrumelo rootstock confers better tolerance to HLB than diploid. Additionally, an even stronger tolerance is achieved when the triploid Persian lime scion is associated.
Temporal heterogeneity in photosystem II photochemistry in Artemisia ordosica under a fluctuating desert environment
Authors: Jin Chuan , Zha Tianshan , Bourque Charles P.-A. , Jia Xin , Tian Yun , Liu Peng , Li Xinhao , Liu Xinyue , Guo Xiaonan , Xu Mingze , Kang Xiaoyu , Guo Zifan , Wang Ning
Published: November 2022

Acclimation strategies in xerophytic plants to stressed environmental conditions vary with temporal scales. Our understanding of environmentally-induced variation in photosystem II (PSII) processes as a function of temporal scales is limited, as most studies have thus far been based on short-term, laboratory-controlled experiments. In a study of PSII processes, we acquired near-continuous, field-based measurements of PSII-energy partitioning in a dominant desert-shrub species, namely Artemisia ordosica, over a six-year period from 2012–2017. Continuous-wavelet transformation (CWT) and wavelet coherence analyses (WTC) were employed to examine the role of environmental variables in controlling the variation in the three main PSII-energy allocation pathways, i.e., photochemical efficiency and regulated and non-regulated thermal dissipation, i.e., ΦPSII, ΦNPQ, and ΦNO, respectively, across a time-frequency domain from hours to years. Convergent cross mapping (CCM) was subsequently used to isolate cause-and-effect interactions in PSII-energy partitioning response. The CWT method revealed that the three PSII-energy allocation pathways all had distinct daily periodicities, oscillating abruptly at intermediate timescales from days to weeks. On a diurnal scale, WTC revealed that all three pathways were influenced by photosynthetically active radiation (PAR), air temperature (Ta), and vapor pressure deficit (VPD). By comparing associated time lags for the three forms of energy partitioning at diurnal scales, revealed that the sensitivity of response was more acutely influenced by PAR, declining thereafter with the other environmental variables, such that the order of influence was greatest for Ta, followed by VPD, and then soil water content (SWC). PSII-energy partitioning on a seasonal scale, in contrast, displayed greater variability among the different environmental variables, e.g., ΦPSII and ΦNO being more predisposed to changes in Ta, and ΦNPQ to changes in VPD. CCM confirmed the causal relationship between pairings of PSII-energy allocation pathways, according to shrub phenology. A. ordosica is shown to have an innate ability to (i) repair damaged PSII-photochemical apparatus (maximum quantum yield of PSII photochemistry, with Fv/Fm > 0.78), and (ii) acclimatize to excessive PAR, dry-air conditions, and prolonged drought. A. ordosica is relatively sensitive to extreme temperature and exhibits photoinhibition.
A poisoned apple: First insights into community assembly and networks of the fungal pathobiome of healthy-looking senescing leaves of temperate trees in mixed forest ecosystem
Authors: Tanunchai Benjawan , Ji Li , Schroeter Simon Andreas , Wahdan Sara Fareed Mohamed , Larpkern Panadda , Lehnert Ann-Sophie , Alves Eliane Gomes , Gleixner Gerd , Schulze Ernst-Detlef , Noll Matthias , Buscot François , Purahong Witoon
Published: November 2022

Despite the abundance of observations of foliar pathogens, our knowledge is severely lacking regarding how the potential fungal pathobiome is structured and which processes determine community assembly. In this study, we addressed these questions by analysing the potential fungal pathobiome associated with the senescing leaves and needles of 12 temperate tree species. We compared fungal plant pathogen load in the senescing leaves/needles and demonstrated that healthy-looking leaves/needles are inhabited by diverse and distinct fungal plant pathogens. We detected 400 fungal plant pathogenic ASVs belonging to 130 genera. The fungal plant pathogenic generalist, Mycosphaerella, was found to be the potential most significant contributor to foliar disease in seedlings. The analyses of assembly process and co-occurrence network showed that the fungal plant pathogenic communities in different tree types are mainly determined by stochastic processes. However, the homogenising dispersal highly contributes in broadleaf trees, whereas ecological drift plays an important role in coniferious trees. The deterministic assembly processes (dominated by variable selection) contributed more in broadleaf trees as compared to coniferous trees. We found that pH and P level significantly corresponded with fungal plant pathogenic community compositions in both tree types. Our study provides the first insight and mechanistic understanding into the community assembly, networks, and complete taxonomy of the foliar fungal pathobiome in senescing leaves and needles.
Atypical patterns of tone production in tone-language-speaking children with autism
Authors: Xu Kunyu , Yan Jinting , Ma Chenlu , Chang Xuhui , Chien Yu-Fu
Published: November 2022

Speakers with autism spectrum disorder (ASD) are found to exhibit atypical pitch patterns in speech production. However, little is known about the production of lexical tones (T1, T2, T3, T4) as well as neutral tones (T1N, T2N, T3N, T4N) by tone-language speakers with ASD. Thus, this study investigated the height and shape of tones produced by Mandarin-speaking children with ASD and their age-matched typically developing (TD) peers. A pronunciation experiment was conducted in which the participants were asked to produce reduplicated nouns. The findings from the acoustic analyses showed that although ASD children generally produced both lexical tones and neutral tones with distinct tonal contours, there were significant differences between the ASD and TD groups for tone height and shape for T1/T1N, T3/T3N, and T4/T4N. However, we did not find any difference in T2/T2N. These data implied that the atypical acoustic pattern in the ASD group could be partially due to the suppression of the F0 range. Moreover, we found that ASD children tended to produce more errors for T2/T2N, T3/T3N than for T1/T1N, T4/T4N. The pattern of tone errors could be explained by the acquisition principle of pitch, similarities among different tones, and tone sandhi. We thus concluded that deficits in pitch processing could be responsible for the atypical tone pattern of ASD children, and speculated that the atypical tonal contours might also be due to imitation deficits. The present findings may eventually help enhance the comprehensive understanding of the representation of atypical pitch patterns in ASD across languages.