bluuebunny/crossref_metadata_2025 huggingface dataset:
Effects of immune checkpoint inhibitor associated endocrinopathies on cancer survival
Authors: Yang Lisa , Murthy Sruthi , Cortellini Alessio , Lim Emma A. , Gonzalez Michael , Pinato David J. , Abdel-Malek Mariana , Mahmoud Sarah , Martin Niamh M.
Published: April 2024

Objectives

Immune checkpoint inhibitors (ICIs) are associated with immune-related adverse events (irAEs), of which endocrinopathies are common. We characterized endocrine and non-endocrine irAEs in cancer patients receiving ICIs, identified risk factors for their development and established whether endocrine and non-endocrine irAEs were differentially associated with improved cancer prognosis.

Design and methods

Single-center, retrospective cohort study of patients with advanced or metastatic solid tumors receiving at least one ICI treatment cycle (242 men, 151 women, median age 65 years). Main outcome measures were incidence of any irAE during the study period, overall survival and time to treatment failure.

Results

Non-endocrine irAEs occurred in 32% and endocrine irAEs in 12% of patients. Primary thyroid dysfunction was the most common endocrine irAE (9.5%) and the majority of endocrinopathies required permanent hormone replacement. Women had an increased risk of developing endocrine irAEs (p = 0.017). The biggest survival advantage occurred in patients who developed both endocrine and non-endocrine irAEs (overall survival: HR 0.16, CI 0.09-0.28). Time to treatment failure was also significantly improved in patients who developed endocrine irAEs (HR 0.49, CI 0.34 – 0.71) or both (HR 0.41, CI 0.25 – 0.64) but not in those who only developed non-endocrine irAEs.

Conclusions

Women may have increased risk of endocrine irAEs secondary to ICI treatment. This is the first study to compare the effects of endocrine irAEs with non-endocrine irAEs on survival. Development of endocrine irAEs may confer survival benefit in ICI treatment and future, prospective studies are needed to elucidate this.
The prevalence and association of measured and perceived indoor air quality, housing characteristics, and residents’ behavior and health
Authors: Gabel Charlotte , Sigsgaard Torben , Petersen Steffen , Elholm Grethe
Published: April 2024

Background

In social housing buildings, poor indoor air quality (IAQ) has been shown to be more prevalent, and residents living in social housing areas are often more vulnerable and susceptible to adverse health effects from IAQ.

Aim

To examine the state and the association of measured and perceived IAQ, how housing characteristics and residents' behavior are associated with IAQ, and the association with residents' health.

Method

The HOME-Health study is a cross-sectional study among residents living in social housing in Denmark (n = 432). Seasonal measurements examined the IAQ by a 14-day period measuring carbon dioxide (CO2), temperature (TP), relative humidity (RH), and air change rate. Residents' self-reported behavior, comfort, and health were obtained from a structured interview.

Results

Thermal discomfort and draught were the most common challenges. During summer, the mean TP was higher, the mean RH was lower, and residents more frequently reported dry air in homes where it was not possible to create cross ventilation. There were a higher mean CO2 and RH when crowdedness increased, particularly during winter. In addition, the proportion of residents reporting dry air was higher when CO2-level was below 1,000 ppm. When the mean RH-level was above 50%, a higher proportion of residents reported experiencing damp air, and when the mean RH-level was below 40% residents more frequently reported dry air. Perception of bad air quality was higher when the mean CO2-level exceeded 1,000 ppm. Additionally, residents reported being most thermally comfortable when the TP was within the range of 20–20.99°C and least comfortable within a range of 22–22.99°C. The residents' perceived experience of impaired IAQ was associated with negative general health symptoms.

Conclusion

It is key that homes have the capability to create cross ventilation in order to allow for proper ventilation and to avoid overheating. When evaluating IAQ it is important to not only consider the measured parameters but to also include the residents' behavior and perception of IAQ as these both are related to the actual IAQ and associated health effects.
Characterization of FBA genes in potato (Solanum tuberosum L.) and expression patterns in response to light spectrum and abiotic stress
Authors: Li Ting , Hou Xinyue , Sun Zhanglun , Ma Bin , Wu Xingxing , Feng Tingting , Ai Hao , Huang Xianzhong , Li Ruining
Published: April 2024

Fructose-1, 6-bisphosphate aldolase (FBA) plays vital roles in plant growth, development, and response to abiotic stress. However, genome-wide identification and structural characterization of the potato (Solanum tuberosum L.) FBA gene family has not been systematically analyzed. In this study, we identified nine StFBA gene members in potato, with six StFBA genes localized in the chloroplast and three in the cytoplasm. The analysis of gene structures, protein structures, and phylogenetic relationships indicated that StFBA genes were divided into Class I and II, which exhibited significant differences in structure and function. Synteny analysis revealed that segmental duplication events promoted the expansion of the StFBA gene family. Promoter analysis showed that most StFBA genes contained cis-regulatory elements associated with light and stress responses. Expression analysis showed that StFBA3, StFBA8, and StFBA9 showing significantly higher expression levels in leaf, stolon, and tuber under blue light, indicating that these genes may improve photosynthesis and play an important function in regulating the induction and expansion of microtubers. Expression levels of the StFBA genes were influenced by drought and salt stress, indicating that they played important roles in abiotic stress. This work offers a theoretical foundation for in-depth understanding of the evolution and function of StFBA genes, as well as providing the basis for the genetic improvement of potatoes.
Association analysis of polymorphisms in SLK, ARHGEF9, WWC2, GAB3, and FSHR genes with reproductive traits in different sheep breeds
Authors: Tao Meini , Li Zhiqiang , Liu Meng , Ma Haiyu , Liu Wujun
Published: April 2024

The aim was to investigate the relationship between polymorphisms of gene mutation loci and reproductive traits in local sheep breeds (Duolang Sheep) and introduced sheep breeds (Suffolk, Hu Sheep) in Xinjiang to provide new molecular markers for the selection and breeding of high fecundity sheep. The expression pattern of typing successful genes in sheep tissues was investigated by RT-qPCR technology, providing primary data for subsequent verification of gene function. The 26 mutation loci of WWC2, ARHGEF9, SLK, GAB3, and FSHR genes were typed using KASP. Association analyses were performed using SPSS 25.0, and the typing results showed that five genes with six loci, WWC2 (g.14962207 C>T), ARHGEF9 (g.48271079 C>A), SLK (g.27107842 T>C, g.27108855 G>A), GAB3 (g.86134602 G>A), and FSHR (g.80789180 T>G) were successfully typed. The results of the association analyses showed that WWC2 (g.14962207 C>T), SLK (g.27108855 G>A), ARHGEF9 (g.48271079 C>A), and FSHR (g.80789180 T>G) caused significant or extremely significant effects on the litter size in Duolang, Suffolk and Hu Sheep populations. The expression distribution pattern of the five genes in 12 sheep reproduction-related tissues was examined by RT-qPCR. The results showed that the expression of the SLK gene in the uterus, the FSHR gene in the ovary, and the ARHGEF9 gene in hypothalamic-pituitary-gonadal axis-related tissues were significantly higher than in the tissues of other parts of the sheep. WWC2 and GAB3 genes were highly expressed both in reproductive organs and visceral tissues. In summary, the WWC2 (g.14962207 C>T), SLK (g.27108855 G>A), ARHGEF9 (g.48271079 C>A), and FSHR (g.80789180 T>G) loci can be used as potential molecular markers for detecting differences in reproductive performance in sheep. Due to variations in typing results, the SLK (g.27107842 T>C) and GAB3 (g.86134602 G>A) loci need further validation.
The role of cGAMP via the STING pathway in modulating germinal center responses and CD4 T cell differentiation
Authors: Yoon Mijung , Choi Yurim , Wi Taeuk , Choi Youn Soo , Choi Jinyong
Published: April 2024

Germinal center (GC) responses are essential for establishing protective, long-lasting immunity through the differentiation of GC B cells (BGC) and plasma cells (BPC), along with the generation of antigen-specific antibodies. Among the various pathways influencing immune responses, the STING (Stimulator of Interferon Genes) pathway has emerged as significant, especially in innate immunity, and extends its influence to adaptive responses. In this study, we examined how the STING ligand cGAMP can modulate these key elements of the adaptive immune response, particularly in enhancing GC reactions and the differentiation of BGC, BPC, and follicular helper T cells (TFH). Employing in vivo models, we evaluated various antigens and the administration of cGAMP in Alum adjuvant, investigating the differentiation of BGC, BPC, and TFH cells, along with the production of antigen-specific antibodies. cGAMP enhances the differentiation of BGC and BPC, leading to increased antigen-specific antibody production. This effect is shown to be type I Interferon-dependent, with a substantial reduction in BPC frequency upon interferon (IFN)-β blockade. Additionally, cGAMP’s influence on TFH differentiation varies over time, which may be critical for refining vaccine strategies. The findings elucidate a complex, antigen-specific influence of cGAMP on T and B cell responses, providing insights that could optimize vaccine efficacy.
Inflammatory cytokine profiles in erectile dysfunction: a bidirectional Mendelian randomization
Authors: Liu Dongze , Qin Zheng , Yi Bocun , Xie Hongbo , Liang Yunan , Zhu Liang , Yang Kuo , Zhang Hongtuan
Published: April 2024

Objectives

Inflammatory cytokines (ICs) play an important role in erectile dysfunction (ED). Previous studies have demonstrated that most ED patients have high levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin-8 (IL-8). The causality between 41 ICs and ED is investigated using the Mendelian randomization (MR) approach.

Methods

Single nucleotide polymorphisms (SNPs) exposure data of 41 ICs came from a genome-wide association study (GWAS) of 8293 subjects. At the same time, the FINNGEN R9 database provided the ED outcome data containing 2205 ED patients and 164104 controls. MR-Egger (ME), inverse variance weighting (IVW), and weighted median (WM) were applied to conduct the MR study and IVW was taken as the main criterion.

Results

From a genetic perspective, the increase of interferon-inducible protein-10 (IP-10) level significantly increased the risk of ED (P=0.043, odds ratio (OR)=1.269, 95% confidence interval (95%CI): 1.007-1.600), while the increase of interleukin-1 receptor antagonist (IL-1RA) markedly decreased the risk of ED (P=0.037, OR=0.768, 95%CI: 0.600-0.984). Meanwhile, IP-10 (p=0.099) and IL-1RA (p=0.135) failed to demonstrate causality in reverse MR analysis.

Conclusions

Changes in ICs levels will significantly affect the risk of ED, especially IP-10 as a risk component for ED and IL-1RA as a protective component for ED. In the future, we can achieve targeted treatment and prevention of ED by intervening with specific inflammatory factors.
Dynamic filtration in baleen whales: recent discoveries and emerging trends
Authors: Werth Alexander J. , Potvin Jean
Published: April 2024

Recent findings have greatly improved our understanding of mysticete oral filtration, and have upended the traditional view of baleen filtration as a simple process. Flow tank experiments, telemetric tag deployment on whales, and other lab and field methods continue to yield new data and ideas. These suggest that several mechanisms arose from ecological, morphological, and biomechanical adaptations facilitating the evolution of extreme body size in Mysticeti. Multiple lines of evidence strongly support a characterization of baleen filtration as a conceptually dynamic process, varying according to diverse intraoral locations and times of the filtration process, and to other prevailing conditions. We review and highlight these lines of evidence as follows. First, baleen appears to work as a complex metafilter comprising multiple components with differing properties. These include major and minor plates and eroded fringes (AKA bristles or hairs), as well as whole baleen racks. Second, it is clear that different whale species rely on varied ecological filtration modes ranging from slow skimming to high-speed lunging, with other possibilities in between. Third, baleen filtration appears to be a highly dynamic and flow-dependent process, with baleen porosity not only varying across sites within a single rack, but also by flow direction, speed, and volume. Fourth, findings indicate that baleen (particularly of balaenid whales and possibly other species) generally functions not as a simple throughput sieve, but instead likely uses cross-flow or other tangential filtration, as in many biological systems. Fifth, evidence reveals that the time course of baleen filtration, including rate of filter filling and clearing, appears to be more complex than formerly envisioned. Flow direction, and possibly plate and fringe orientation, appears to change during different stages of ram filtration and water expulsion. Sixth, baleen’s flexibility and related biomechanical properties varies by location within the whole filter (=rack), leading to varying filtration conditions and outcomes. Seventh, the means of clearing/cleaning the baleen filter, whether by hydraulic, hydrodynamic, or mechanical methods, appears to vary by species and feeding type, notably intermittent lunging versus continuous skimming. Together, these and other findings of the past two decades have greatly elucidated processes of baleen filtration, and heightened the need for further research. Many aspects of baleen filtration may pertain to other biological filters; designers can apply several aspects to artificial filtration, both to better understand natural systems and to design and manufacture more effective synthetic filters. Understanding common versus unique features of varied filtration phenomena, both biological and artificial, will continue to aid scientific and technical understanding, enable fruitful interdisciplinary partnerships, and yield new filter designs.
Biomimetic spray coating for fruit preservation based on UiO-1 67 metal–organic framework nanozyme
Authors: Li Jie , Wang Donglin , Liu Yuhang
Published: April 2024

The application of edible coatings for preparing composite antibacterial spray coatings for fruit preservation by incorporating antibacterial nanoparticles has gained increasing attention. Chitosan (CS) is a natural polysaccharide used as an edible coating to preserve fruit; it has properties such as reducing water loss, enhancing appearance, and improving mechanical properties. By combining it with antibacterial material, it can reduce fruit microorganisms. Cerium (Ce) has excellent antibacterial activity combined with the advantages of safety and low cost. Therefore, this study proposes a biocatalytic spray coating for fruit preservation using a CS composite metal–organic framework (CS@Ce-MOF) with strawberry as a model fruit. CS@Ce-MOFs are superior to Ce-MOFs in the aqueous stability of their chemical structure, inoxidizability, antibacterial duration, and validity. The well-characterized CS@Ce-MOF was verified to simultaneously mimic good oxidase- and apyrase-like activities. CS@Ce-MOF biocatalytic spray coating demonstrated excellent antibacterial properties against two common foodborne pathogens: Escherichia coli and the Gram-positive bacterium Staphylococcus aureus, with high killing rates of up to 94.5%. This is due to the unique structure of the CS@Ce-MOF composite, which presents a large surface area for contact with pathogens and enhances the catalytic activity of the incorporated cerium oxide nanoparticles, leading to efficient sterilization. Furthermore, the scavenging rate of DPPH and ABTS free radicals is more than 80%, indicating that CS@Ce-MOF has excellent antioxidant properties. Moreover, CS@Ce-MOF minimized the weight loss and firmness of strawberries and bananas over 7 days of ambient storage. The use of such a biocatalytic spray coating has enormous potential for preserving the quality and safety of fresh produce, reducing food waste, and promoting sustainable agricultural practices.
IgM kappa proliferative glomerulonephritis with monoclonal immunoglobulin deposition complicated with nocardiosis dermatitis: a case report and review of literature
Authors: Chen Kebao , Wang Yue , Yu Jinyu , Wang Xueyao , Xu Zhonggao , Li Yanbo , Sun Weixia
Published: April 2024

Rationale

Monoclonal gammopathy of renal significance (MGRS) represents a group of disorders caused by monoclonal immunoglobulin (M protein) secreted by B cells or plasma cells. Proliferative glomerulonephritis with monoclonal immunoglobulin deposition (PGNMID) is a glomerular disease and a form of MGRS. Here, we presented a rare case of a patient with IgM kappa PGNMID complicated with nocardiosis dermatitis.

Patient concerns and diagnoses

A 56-year-old man was admitted to the hospital because of cutaneous purpura and proteinuria. His initial pathological diagnosis indicated membranous proliferative glomerulonephritis, IgM(++), and subacute interstitial nephritis. Based on further examination, he was finally diagnosed to have IgM kappa PGNMID and subacute interstitial nephritis. After the initial diagnosis, the patient received hormonal therapy. During the treatment, nocardiosis dermatitis emerged as a complication, and the hormonal therapy was gradually reduced. The patient refused further treatment with rituximab, and his health is currently stable.

Outcomes

IgM kappa PGNMID complicated with nocardiosis dermatitis is an extremely rare occurrence. Laboratory examination and pathological analysis are required to confirm the diagnosis of this disorder. Timely and accurate diagnosis is essential for the appropriate treatment of PGNMID.
Synthetic polypeptides using a biologic as a reference medicinal product – the European landscape of regulatory approvals
Authors: Klein Kevin , Heisterberg Jens , Stolk Pieter
Published: April 2024

Recent advances in synthetic drug manufacturing have introduced a new dynamic to the European regulatory system, with chemically synthesized polypeptide products using biological originator products as their reference medicine. Whereas biosimilars are subject to a dedicated regulatory framework in the EU, synthetically produced follow-on products are not eligible for assessment through this pathway, requiring approval via the traditional generic pathway under Article 10 (1), or via the hybrid pathway under Article 10 (3). This review presents an overview of recent developments in the field of synthetic peptides referencing biological originators in the EU. The use of different regulatory procedures can have potential implications for regulatory assessments, clinical practice and pharmacovigilance. As more complex synthetic products referencing recombinant originator products are expected in the coming years, this study promotes more transparency as well as global alignment about regulatory procedures for chemically synthesised products referencing biological originator products to ensure approval of safe and high-quality generics.
Does intraoperative reduction result in better outcomes in low-grade lumbar spondylolisthesis after transforaminal lumbar interbody fusion? A systematic review and meta-analysis
Authors: Qin Rongqing , Zhu Min , Zhou Pin , Guan Anhong
Published: April 2024

Objective

This study aimed to compare the clinical efficacy and safety of reduction vs. arthrodesis in situ with transforaminal lumbar interbody fusion (TLIF) for low-grade lumbar spondylolisthesis.

Study design

Systematic review and meta-analysis.

Methods

A comprehensive literature search was implemented in PubMed, Embase, and Cochrane Library databases. Randomized or non-randomized controlled trials that were published until July 2023 that compared reduction vs. arthrodesis in situ techniques with minimally invasive or open-TLIF for low-grade spondylolisthesis were selected. The quality of the included studies was evaluated by the Newcastle–Ottawa Scale (NOS). Data were extracted according to the predefined outcome measures, including operation time and intraoperative blood loss; short- and long-time follow-up of visual analog scale (VAS) back pain (VAS-BP) and Oswestry Disability Index (ODI); slippage and segmental lordosis; and the complication and fusion rate.

Results

Five studies (n = 495 patients) were finally included. All of them were retrospective cohort studies with Evidence Level II. The pooled data revealed that both techniques had similar patient-reported outcomes (VAS, ODI, and good and excellent rate) during short- and long-term follow-up. In addition, no significant differences were observed in the fusion and complication rates. However, although the reduction group did achieve better slippage correction, it was associated with increased operation time and intraoperative blood loss compared with the in situ arthrodesis group.

Conclusions

Based on the available evidence, intraoperative reduction does not result in better clinical outcomes in low-grade spondylolisthesis after minimally invasive or open-TLIF, and the in situ arthrodesis technique could be an alternative.
Bacteria from nodules of Abrus mollis Hance: genetic diversity and screening of highly efficient growth-promoting strains
Authors: Cao Kexin , Chen Jianhua , Li Qiuling , Gu Peng , Li Liangbo , Huang Rongshao
Published: April 2024

Introduction

Abrus mollis Hance. (AM) is an important species used in southern Chinese medicine. It is mainly found in Guangdong and Guangxi provinces in China, and it is effective in the treatment of hepatitis. Endophytic bacteria are known to affect the growth and quality of medicinal plants. However, there are limited reports describing endophytic bacteria related to AM.

Methods

In the present study, Illumina-based 16S rRNA gene sequencing was used to investigate the endophytic bacterial communities of root nodules of AM at five sampling sites in Guangxi. In addition, 179 strains of endophytic bacteria were isolated and categorized into 13 haplotypes based on recA sequence analysis.

Results

The phylogeny of the 16S rRNA gene sequences revealed a predominance of nonrhizobial endophytes. Microbial diversity analysis showed that Proteobacteria was the dominant phylum in all samples, while Bradyrhizobium was the dominant genus in different samples. An efficient strain, Rhizobium tropici FM-19, was screened and obtained through greenhouse experiments. The AM plants inoculated with this strain showed the best growth performance and high nitrogen fixation and nodulation capacity. Notably, total phenols and total flavonoids, important active components in AM, increased by 30.9 and 42.7%, respectively, after inoculation with Rhizobium tropici FM-19.

Discussion

This study provides insights into the complex microbial diversity of AM nodules and provides strain information for the efficient cultivation of AM.
Deorphanizing solute carriers in Saccharomyces cerevisiae for secondary uptake of xenobiotic compounds
Authors: Møller-Hansen Iben , Sáez-Sáez Javier , van der Hoek Steven A. , Dyekjær Jane D. , Christensen Hanne B. , Wright Muelas Marina , O’Hagan Steve , Kell Douglas B. , Borodina Irina
Published: April 2024

The exchange of small molecules between the cell and the environment happens through transporter proteins. Besides nutrients and native metabolic products, xenobiotic molecules are also transported, however it is not well understood which transporters are involved. In this study, by combining exo-metabolome screening in yeast with transporter characterization in Xenopus oocytes, we mapped the activity of 30 yeast transporters toward six small non-toxic substrates. Firstly, using LC–MS, we determined 385 compounds from a chemical library that were imported and exported by S. cerevisiae. Of the 385 compounds transported by yeast, we selected six compounds (viz. sn-glycero-3-phosphocholine, 2,5-furandicarboxylic acid, 2-methylpyrazine, cefadroxil, acrylic acid, 2-benzoxazolol) for characterization against 30 S. cerevisiae xenobiotic transport proteins expressed in Xenopus oocytes. The compounds were selected to represent a diverse set of chemicals with a broad interest in applied microbiology. Twenty transporters showed activity toward one or more of the compounds. The tested transporter proteins were mostly promiscuous in equilibrative transport (i.e., facilitated diffusion). The compounds 2,5-furandicarboxylic acid, 2-methylpyrazine, cefadroxil, and sn-glycero-3-phosphocholine were transported equilibratively by transporters that could transport up to three of the compounds. In contrast, the compounds acrylic acid and 2-benzoxazolol, were strictly transported by dedicated transporters. The prevalence of promiscuous equilibrative transporters of non-native substrates has significant implications for strain development in biotechnology and offers an explanation as to why transporter engineering has been a challenge in metabolic engineering. The method described here can be generally applied to study the transport of other small non-toxic molecules. The yeast transporter library is available at AddGene (ID 79999).
Fermentation properties and functional stability of dough starter Jiaozi and Laomian after frozen storage
Authors: Li Haifeng , Lv Yulan , Zhang Yingmiao , Wang Xifeng , Yang Xiaohong , Qu Jianhang
Published: April 2024

Purpose

This study aims to investigate the effects of frozen storage on the stability of traditional dough starters in China.

Methods

The microbial community structure and abundance of related metabolic genes in different fermented sourdough prepared by Jiaozi (JZ) and Laomian (LM) starters before and after frozen storage at −20°C for half a year were analyzed using the shotgun metagenomic sequencing method, and differences in characteristics of texture in steamed bread were also compared by formal methods.

Results

The fermentation ability (FA) and metabolic activities of yeast in the JZH sourdough (started by JZ which was stored at −20°C for half a year) were better than those of LMH sourdough (started by LM which was stored at −20°C for half a year). The dominant genera of Acetobacter were found to be increased in the JZH0 sourdough (started by JZH and fermented for 0 h) and those of Lactobacillus were found to be decreased. Lactobacillus (98.72%), Pediococcus (0.37%), Saccharomyces (0.27%), and Acetobacter (0.01%), were dominant in sourdough LMH0 (started by LMH and fermented for 0 h). The abundances of “oxidative phosphorylation-related enzymes” and the “biosynthesis of glutamate”-related enzymes and genes related to “biosynthesis of glutamate” and “unsaturated fatty acid” were higher in JZH0 than in the JZ0 sourdough (started by JZ without being frozen and fermented for 0 h). The good FA of yeast, the acid production capacity of bacteria in the sourdough, and the quality of the JZH steamed bread (made by the JZH starter) indicated the better freezing tolerance of the microorganisms in JZ than in LM.

Conclusion

The conclusion of this study suggests the better application potential of the JZ as the fermentation starter in actual production.
Understanding and exploring the diversity of soil microorganisms in tea (Camellia sinensis) gardens: toward sustainable tea production
Authors: Jibola-Shittu Motunrayo Y. , Heng Zhiang , Keyhani Nemat O. , Dang Yuxiao , Chen Ruiya , Liu Sen , Lin Yongsheng , Lai Pengyu , Chen Jinhui , Yang Chenjie , Zhang Weibin , Lv Huajun , Wu Ziyi , Huang Shuaishuai , Cao Pengxi , Tian Lin , Qiu Zhenxing , Zhang Xiaoyan , Guan Xiayu , Qiu Junzhi
Published: April 2024

Leaves of Camellia sinensis plants are used to produce tea, one of the most consumed beverages worldwide, containing a wide variety of bioactive compounds that help to promote human health. Tea cultivation is economically important, and its sustainable production can have significant consequences in providing agricultural opportunities and lowering extreme poverty. Soil parameters are well known to affect the quality of the resultant leaves and consequently, the understanding of the diversity and functions of soil microorganisms in tea gardens will provide insight to harnessing soil microbial communities to improve tea yield and quality. Current analyses indicate that tea garden soils possess a rich composition of diverse microorganisms (bacteria and fungi) of which the bacterial Proteobacteria, Actinobacteria, Acidobacteria, Firmicutes and Chloroflexi and fungal Ascomycota, Basidiomycota, Glomeromycota are the prominent groups. When optimized, these microbes’ function in keeping garden soil ecosystems balanced by acting on nutrient cycling processes, biofertilizers, biocontrol of pests and pathogens, and bioremediation of persistent organic chemicals. Here, we summarize research on the activities of (tea garden) soil microorganisms as biofertilizers, biological control agents and as bioremediators to improve soil health and consequently, tea yield and quality, focusing mainly on bacterial and fungal members. Recent advances in molecular techniques that characterize the diverse microorganisms in tea gardens are examined. In terms of viruses there is a paucity of information regarding any beneficial functions of soil viruses in tea gardens, although in some instances insect pathogenic viruses have been used to control tea pests. The potential of soil microorganisms is reported here, as well as recent techniques used to study microbial diversity and their genetic manipulation, aimed at improving the yield and quality of tea plants for sustainable production.
Cognitive reserve over the life course and risk of dementia: a systematic review and meta-analysis
Authors: Liu Yulu , Lu Guangyu , Liu Lin , He Yuhang , Gong Weijuan
Published: April 2024

Background

The number of people with dementia is soaring. Cognitive reserve has been thought to be associated with dementia risk. It is not clear at which period in the life course and which cognitive reserve proxies contribute to the reduced risk of dementia.

Methods

By scanning four databases (PubMed, Embase, Web of Science, and MEDLINE) up to Jun 3, 2023, longitudinal studies of life-course cognitive reserve and risk of dementia were found. The HRs and 95% CIs for each study were summarized using random effects models. Subgroup analyses and sensitivity analyses were conducted. Utilizing funnel plots, Begg and Egger tests, publication bias was investigated.

Results

A total of 27 studies were included, containing 10 in early-life, 10 in middle-life, and 13 in late-life. All studies used validated questionnaires to measure cognitive reserve, and dementia diagnosis followed recognized worldwide guidelines. All included studies were of medium or low risk. Cognitive reserve in early-life (Hazard ratio (HR): 0.82; 95% confidence interval (CI): 0.79–0.86), middle-life (HR: 0.91; 95% CI: 0.84–0.98) and late-life (HR: 0.81; 95% CI: 0.75–0.88) all have protective effects on dementia risk. Multiple sensitivity analyses showed consistent results.

Conclusion

Dementia risk is reduced by the buildup of cognitive reserves during life-course. Accumulation of proxies for cognitive reserve in early and late life had the greatest effect on dementia risk reduction. Social connection may be an effective approach to lower dementia risk.
Orexins in apoptosis: a dual regulatory role
Authors: Cavalu Simona , Saber Sameh , Hamad Rabab S. , Abdel-Reheim Mustafa Ahmed , Elmorsy Elsayed A. , Youssef Mahmoud E.
Published: April 2024

The orexins, also referred to as hypocretins, are neuropeptides that originate from the lateral hypothalamus (LH) region of the brain. They are composed of two small peptides, orexin-A, and orexin-B, which are broadly distributed throughout the central and peripheral nervous systems. Orexins are recognized to regulate diverse functions, involving energy homeostasis, the sleep-wake cycle, stress responses, and reward-seeking behaviors. Additionally, it is suggested that orexin-A deficiency is linked to sleepiness and narcolepsy. The orexins bind to their respective receptors, the orexin receptor type 1 (OX1R) and type 2 (OX2R), and activate different signaling pathways, which results in the mediation of various physiological functions. Orexin receptors are widely expressed in different parts of the body, including the skin, muscles, lungs, and bone marrow. The expression levels of orexins and their receptors play a crucial role in apoptosis, which makes them a potential target for clinical treatment of various disorders. This article delves into the significance of orexins and orexin receptors in the process of apoptosis, highlighting their expression levels and their potential contributions to different diseases. The article offers an overview of the existing understanding of the orexin/receptor system and how it influences the regulation of apoptosis.
Age-related differences in auditory spatial processing revealed by acoustic change complex
Authors: Wang Xing , Nie Shuai , Wen Yining , Zhao Zihui , Li Jiaying , Wang Ningyu , Zhang Juan
Published: April 2024

Objectives

The auditory spatial processing abilities mature throughout childhood and degenerate in older adults. This study aimed to compare the differences in onset cortical auditory evoked potentials (CAEPs) and location-evoked acoustic change complex (ACC) responses among children, adults, and the elderly and to investigate the impact of aging and development on ACC responses.

Design

One hundred and seventeen people were recruited in the study, including 57 typically-developed children, 30 adults, and 30 elderlies. The onset-CAEP evoked by white noise and ACC by sequential changes in azimuths were recorded. Latencies and amplitudes as a function of azimuths were analyzed using the analysis of variance, Pearson correlation analysis, and multiple linear regression model.

Results

The ACC N1’-P2’ amplitudes and latencies in adults, P1’-N1’ amplitudes in children, and N1’ amplitudes and latencies in the elderly were correlated with angles of shifts. The N1’-P2’ and P2’ amplitudes decreased in the elderly compared to adults. In Children, the ACC P1’-N1’ responses gradually differentiated into the P1’-N1’-P2’ complex. Multiple regression analysis showed that N1’-P2’ amplitudes (R2 = 0.33) and P2’ latencies (R2 = 0.18) were the two most variable predictors in adults, while in the elderly, N1’ latencies (R2 = 0.26) explained most variances. Although the amplitudes of onset-CAEP differed at some angles, it could not predict angle changes as effectively as ACC responses.

Conclusion

The location-evoked ACC responses varied among children, adults, and the elderly. The N1’-P2’ amplitudes and P2’ latencies in adults and N1’ latencies in the elderly explained most variances of changes in spatial position. The differentiation of the N1’ waveform was observed in children. Further research should be conducted across all age groups, along with behavioral assessments, to confirm the relationship between aging and immaturity in objective ACC responses and poorer subjective spatial performance.

Significance

ACCs evoked by location changes were assessed in adults, children, and the elderly to explore the impact of aging and development on these differences.
ExaFlexHH: an exascale-ready, flexible multi-FPGA library for biologically plausible brain simulations
Authors: Miedema Rene , Strydis Christos
Published: April 2024

Introduction

In-silico simulations are a powerful tool in modern neuroscience for enhancing our understanding of complex brain systems at various physiological levels. To model biologically realistic and detailed systems, an ideal simulation platform must possess: (1) high performance and performance scalability, (2) flexibility, and (3) ease of use for non-technical users. However, most existing platforms and libraries do not meet all three criteria, particularly for complex models such as the Hodgkin-Huxley (HH) model or for complex neuron-connectivity modeling such as gap junctions.

Methods

This work introduces ExaFlexHH, an exascale-ready, flexible library for simulating HH models on multi-FPGA platforms. Utilizing FPGA-based Data-Flow Engines (DFEs) and the dataflow programming paradigm, ExaFlexHH addresses all three requirements. The library is also parameterizable and compliant with NeuroML, a prominent brain-description language in computational neuroscience. We demonstrate the performance scalability of the platform by implementing a highly demanding extended-Hodgkin-Huxley (eHH) model of the Inferior Olive using ExaFlexHH.

Results

Model simulation results show linear scalability for unconnected networks and near-linear scalability for networks with complex synaptic plasticity, with a 1.99 × performance increase using two FPGAs compared to a single FPGA simulation, and 7.96 × when using eight FPGAs in a scalable ring topology. Notably, our results also reveal consistent performance efficiency in GFLOPS per watt, further facilitating exascale-ready computing speeds and pushing the boundaries of future brain-simulation platforms.

Discussion

The ExaFlexHH library shows superior resource efficiency, quantified in FLOPS per hardware resources, benchmarked against other competitive FPGA-based brain simulation implementations.
Utilization of a novel patient-specific 3D-printing template for percutaneous endoscopic transforaminal discectomy: results from a randomized controlled trial
Authors: Huang Xin , Luo Qipeng , Liang Chen , Wang Yixuan , Jia Donglin , Li Shuiqing , Guo Xiangyang
Published: April 2024

Background

The learning curve for percutaneous endoscopic transforaminal discectomy (PETD) is steep, especially for the puncturing and localization procedures. The implementation of 3D printing technology may solve this problem.

Methods

A novel individualized 3D-printing template (3D-PT) was designed and utilized in PETD. A prospective randomized controlled trial was performed. A total of 28 patients with lumbar disc herniation treated with PETD were analyzed. Of these, 14 patients were treated with the assistance of 3D printing technology (3D-PT group) in conjunction with fluoroscopy, while the remaining 14 patients were treated exclusively under the guidance of C-arm fluoroscopy (control group).

Results

The number of puncture attempts in the 3D-PT group was significantly less than in the control group (1.36 ± 0.63 vs. 6.07 ± 3.08, p = 0.000). The 3D-PT group exhibited a significant reduction in both intraoperative puncture fluoroscopies (2.71 ± 1.27 vs. 12.14 ± 6.15, p = 0.000) and the overall number of fluoroscopies (2.71 ± 1.27 vs. 17.43 ± 6.27, p = 0.000). In the 3D-PT group, there was a significant reduction in both the puncture time (5.77 ± 1.82 vs. 13.99 ± 4.36, p = 0.000) and the total operation time (60.39 ± 9.78 vs. 76.25 ± 17.78, p = 0.007). Complications were not observed in either group.

Conclusion

The application of the novel individualized 3D-PT for PETD is effective and safe. The technique has substantial potential and is worth widely promoting.
Xie Zhuo Tiao Zhi formula ameliorates chronic alcohol-induced liver injury in mice
Authors: Chang Kaixin , Guo Rui , Hu Wenbo , Wang Xuezhu , Cao Feiwei , Qiu Jiannan , Li Jiaomei , Han Qiang , Du Zhongyan , Dou Xiaobing , Li Songtao
Published: April 2024

This study aimed to evaluate the protective role and potential mechanisms of Xie Zhuo Tiao Zhi decoction (XZTZ) on alcohol-associated liver disease (ALD). XZTZ significantly alleviated alcohol-induced liver dysfunction, based on histological examinations and biochemical parameters after 4-week administration. Mechanically, alcohol-stimulated hepatic oxidative stress was ameliorated by XZTZ, accompanied by the improvement of Nrf2/Keap1 expression and alcohol-activated phosphorylation of pro-inflammatory transcription factors, including JNK, P38, P65, and IκBα, were rescued by XZTZ. In conclusion, XZTZ demonstrates potential in alleviating alcohol-induced liver injury, oxidative stress, and inflammation possibly through modulation of Nrf2/Keap1 and MAPKs/NF-κB signaling pathways, suggesting its potential as a therapeutic option for patients with alcoholic liver disease.
Postgraduate education and training in drug development sciences: 30 years of the european center of pharmaceutical medicine
Authors: Mollet Annette , Laskowski Nastazja , Szucs Thomas
Published: April 2024

The European Center of Pharmaceutical Medicine (ECPM), affiliated with the University of Basel Department of Public Health, stands as a leading institution dedicated to advancing education in medicine development since 1991. At the heart of its educational offers lies the Diploma or Certificate (DAS or CAS) in Pharmaceutical Medicine, encompassing a comprehensive curriculum that covers the entire drug development process. ECPM has expanded its reach beyond Switzerland, offering courses in the USA, China and India. Through rigorous teaching and strategic alliances, ECPM continues to shape education in pharmaceutical medicine on an international scale.
Small molecule drug discovery for glioblastoma treatment based on bioinformatics and cheminformatics approaches
Authors: Feng Liya , Zhu Sha , Ma Jian , Huang Jing , Hou Xiaoyan , Qiu Qian , Zhang Tingting , Wan Meixia , Li Juan
Published: April 2024

Background: Glioblastoma (GBM) is a common and highly aggressive brain tumor with a poor prognosis for patients. It is urgently needed to identify potential small molecule drugs that specifically target key genes associated with GBM development and prognosis.

Methods: Differentially expressed genes (DEGs) between GBM and normal tissues were obtained by data mining the Gene Expression Omnibus (GEO) and The Cancer Genome Atlas (TCGA) databases. Gene function annotation was performed to investigate the potential functions of the DEGs. A protein-protein interaction (PPI) network was constructed to explore hub genes associated with GBM. Bioinformatics analysis was used to screen the potential therapeutic and prognostic genes. Finally, potential small molecule drugs were predicted using the DGIdb database and verified using chemical informatics methods including absorption, distribution, metabolism, excretion, toxicity (ADMET), and molecular docking studies.

Results: A total of 429 DEGs were identified, of which 19 hub genes were obtained through PPI analysis. The hub genes were confirmed as potential therapeutic targets by functional enrichment and mRNA expression. Survival analysis and protein expression confirmed centromere protein A (CENPA) as a prognostic target in GBM. Four small molecule drugs were predicted for the treatment of GBM.

Conclusion: Our study suggests some promising potential therapeutic targets and small molecule drugs for the treatment of GBM, providing new ideas for further research and targeted drug development.
Phosphatidic acid produced by phospholipase Dα1 and Dδ is incorporated into the internal membranes but not involved in the gene expression of RD29A in the abscisic acid signaling network in Arabidopsis thaliana
Authors: Ndathe Ruth , Kato Naohiro
Published: April 2024

Core protein components of the abscisic acid (ABA) signaling network, pyrabactin resistance (PYR), protein phosphatases 2C (PP2C), and SNF1-related protein kinase 2 (SnRK2) are involved in the regulation of stomatal closure and gene expression downstream responses in Arabidopsis thaliana. Phosphatidic acid (PA) produced by the phospholipases Dα1 and Dδ (PLDs) in the plasma membrane has been identified as a necessary molecule in ABA-inducible stomatal closure. On the other hand, the involvement of PA in ABA-inducible gene expression has been suggested but remains a question. In this study, the involvement of PA in the ABA-inducible gene expression was examined in the model plant Arabidopsis thaliana and the canonical RD29A ABA-inducible gene that possesses a single ABA–responsive element (ABRE) in the promoter. The promoter activity and accumulation of the RD29A mRNA during ABA exposure to the plants were analyzed under conditions in which the production of PA by PLDs is abrogated through chemical and genetic modification. Changes in the subcellular localization of PA during the signal transduction were analyzed with confocal microscopy. The results obtained in this study suggest that inhibition of PA production by the PLDs does not affect the promoter activity of RD29A. PA produced by the PLDs and exogenously added PA in the plasma membrane are effectively incorporated into internal membranes to transduce the signal. However, exogenously added PA induces stomatal closure but not RD29A expression. This is because PA produced by the PLDs most likely inhibits the activity of not all but only the selected PP2C family members, the negative regulators of the RD29A promoter. This finding underscores the necessity for experimental verifications to adapt previous knowledge into a signaling network model before its construction.
Investigating the effect of grit trait on performance and success in Hungarian athlete’s sample
Authors: Apró Annamária , Fejes Nikoletta , Bandi Szabolcs A. , Járai Róbert
Published: April 2024

Background

The aim of the present study is to translate the Grit questionnaire into Hungarian and validate specifically within the context of sports. The second goal is to assess the questionnaire in Hungarian as a pilot study in the athlete population and to compare the grit trait with the coaches’ athlete evaluation.

Methods

Two hundred and sixty nine athletes, including 40 national team players, took part in the study, with an average age of 18.17 years (SD = 5.51). For the preliminary assessment, the Cloninger Temperament and Character Questionnaire (TCI-RH) was used; the coaches’ athlete evaluation was modeled on a talent map.

Results

The confirmatory factor analysis confirmed the fit of the two-factor structure, and the internal reliability of the questionnaire scales also proved to be adequate. 2. There is no relationship between adolescents’ perceived grit and coach ratings. 3. The national team players achieved a higher grit score.

Conclusion

Based on the psychometric indicators, the validity and reliability of the questionnaire proved to be adequate. Therefore, it is applicable and useful for psychological practitioners and researchers in the Hungarian population within the context of sports.