Metabolic determinants of germinal center B cell formation and responses.

Germinal center (GC) B cells are crucial for the generation of GCs and long-lived humoral immunity. Here we report that one-carbon metabolism determines the formation and responses of GC B cells. Upon CD40 stimulation, GC B cells selectively upregulate methylenetetrahydrofolate dehydrogenase 2 (MTHFD2) expression to generate purines and the antioxidant glutathione. MTHFD2 depletion reduces GC B cell frequency and antigen-specific antibody production. Moreover, supplementation with nucleotides and antioxidants suffices to promote GC B cell formation and function in vitro and in vivo through activation of the mammalian target of rapamycin complex 1 signaling pathway. Moreover, we found that antigen stimulation enhances YY1 binding to the Mthfd2 promoter and promotes MTHFD2 transcription. Interestingly, these findings can be generalized to the pentose phosphate pathway, which is another major source of reducing power and nucleotides. Therefore, these results suggest that an increased capacity for nucleotide synthesis and redox balance is required for GC B cell formation and responses, revealing a key aspect of GC B cell fate determination.

Posture planning method for complex feature measurement using a single-line laser scanner.

A single-line laser scanner is commonly utilized for measuring complex surfaces and contours. However, achieving automatic implementation of this scanner poses challenges in terms of designing a measurement posture that considers measurement accuracy, path planning, and the positioning of auxiliary equipment. This ensures non-interference during the measurement process. In this study, we focus on the application of T-SCAN. First, we construct a measurement posture parameter model for T-SCAN and analyze the viewpoint position's coverage of the measurement area. Second, we propose a measurement path planning method based on scanning posture to minimize overlapping areas. Lastly, we present a measurement station planning method based on scanning postures and analyze the transfer error of the measurement targets to establish a unified measurement field. Experimental results demonstrate that, after the posture adjustment process, the average distance deviation between the measurement data and the theoretical model is significantly reduced.

Infection of Trichinella spiralis Affects the Reproductive Capacity of ICR/CD-1 Male Mice by Reducing the Urine Pheromone Contents and Sperm Quality.

Female mice can discriminate the urinary odors of male mice due to their olfactory acuity. Parasitic infection or subclinical infection can decrease the odor attractiveness of male mice and finally lead to aversion or avoidance responses in odor selection for female mice. Trichinella spiralis is a kind of tissue-parasitizing nematode that causes trichinellosis, a zoonotic parasitic disease that spreads throughout the world. However, the reproductive injury caused by Trichinella spiralis infection was not fully revealed. In this study, we explored the effect of Trichinella spiralis infection on the reproductive capacity in ICR/CD-1 male mice. We identified eight volatile compounds in urine by GC-MS analysis, and the results indicated that the contents of dimethyl sulfone, Z-7-tetradecen-1-ol, 6-Hydroxy-6-methyl-3-heptanone and (S)-2-sec-butyl-4,5-dihydrothiazole were significantly downregulated after parasitic infection, which might lead to the reduction of attractiveness of male mice urine to females. On the other hand, parasitic infection decreased sperm quality and downregulated the expression levels of Herc4, Ipo11, and Mrto4, and these genes were strongly related to spermatogenesis. In summary, this study revealed that the reproductive injury caused by Trichinella spiralis infection in ICR/CD-1 male mice could be associated with a decrease in urine pheromone content and sperm quality.

Schistosoma japonicum infection associated with membranous nephropathy: a case report.

BACKGROUND: Schistosomiasis is one of the most contagious parasitic diseases affecting humans; however, glomerular injury is a rare complication mainly described with Schistosoma mansoni infection. We report a case of membranous nephropathy associated with Schistosoma japonicum infection in a Chinese man. CASE PRESENTATION: A 51-year-old Chinese male with a long history of S. japonicum infection presented to the hospital with a slowly progressing severe lower limb edema and foaming urine for over 5 months. Serum S. japonicumantigen test was positive and immunohistochemistry showed that the glomeruli were positive for the antigens. The renal pathologic diagnosis was stage III membranous nephropathy. The patient was treated with glucocorticoid, praziquantel, and an angiotensin-converting enzyme inhibitor. The edema in both lower limbs disappeared within 2 weeks, but his renal function declined progressively and proteinuria persisted after 5 months of therapy. CONCLUSIONS: Different classes of schistosomal glomerulopathy have completely different clinical manifestation and prognosis. Therefore, efforts should focus on alleviating symptoms, prevention, and early detection. S. japonicumassociated with membranous nephropathy may show a good curative effect and prognosis. However, it is necessary to monitor the renal function in such patients.

Correction to: Emerging technologies for the pretreatment of lignocellulosic materials for bio-based products.

This corrects the article "Emerging technologies for the pretreatment of lignocellulosic materials for bio-based products" in volume 104, with page no 455-473, (https://doi.org/10.1007/s00253-019-10158-w).

Emerging technologies for the pretreatment of lignocellulosic materials for bio-based products.

Exploring a cheap and clean renewable energy has become a common destination round the world with the depletion of oil resources and the concerns of increasing energy demands. Lignocellulosic biomass is the most abundant renewable resource in the biosphere, and the total biomass formed by plant photosynthesis reached more than 200 billion tons every year. Cellulase and hemicellulose and lignin degradation enzymes, the efficient biocatalyst, could efficiently convert the lignocellulosic biomass into sugars that could be further processed into biofuels, biochemical, and biomaterial for human requirement. The utilization and conversion of cellulosic biomass has great significance to solve the problems such as environmental pollution and energy crisis. Lignocellulosic materials are widely considered as important sources to produce sugar streams that can be fermented into ethanol and other organic chemicals. Pretreatment is a necessary step to overcome its intrinsic recalcitrant nature prior to the production of important biomaterial that has been investigated for nearly 200 years. Emerging research has focused in order of economical, eco-friendly, and time-effective solutions, for large-scale operational approach. These new mentioned technologies are promising for lignocellulosic biomass degradation in a huge scale biorefinery. This review article has briefly explained the emerging technologies especially the consolidated bioprocessing, chemistry, and physical base pretreatment and their importance in the valorization of lignocellulosic biomass conversion.

Turning rural villages into the home front for social stability-Examination of coronavirus disease 2019 control experiences in rural areas in China.

Since the outbreak of COVID-19, the disease has continued to spread and countries around the world have been plagued by its causal agent, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the comprehensive fight against the SARS-CoV-2, China has taken a series of important measures, achieved major victories in safeguarding people's lives and health, and accumulated important experience. Rural epidemic prevention and control is a basic part of the entire prevention and control system, with certain particularities. This study summarizes China's experience in preventing and controlling COVID-19 and the local measures taken to effectively prevent the spread of the disease in rural areas. All countries worldwide can learn from China's experience and take measures according to their own national and local conditions to effectively achieve the rural prevention and control of COVID-19. Meanwhile, the crisis itself can be viewed as a new opportunity for rural development.

Effect of Lactobacillus acidophilus KLDS 1.0738 on miRNA expression in in vitro and in vivo models of ß-lactoglobulin allergy.

This study aims to investigate the correlation between the ability of L. acidophilus to modulate miRNA expression and prevent Th17-dominated ß-lactoglobulin (ß-Lg) allergy. In vitro immunomodulation was evaluated by measuring splenocyte proliferation, Th17-related immune response and miRNA expression in ß-Lg-sensitized splenocytes cultured with live L. acidophilus. Next, the allergic mouse model was used to evaluate anti-allergy capability of lactobacilli. The ß-Lg challenge led to induction of up-regulation of miR-146a, miR-155, miR-21 and miR-9 expression in both in vivo and in vitro, along with increased Th17-related cytokine levels and mRNA expression of RORγt and IL-17. However, treatment of live L. acidophilus significantly suppressed hypersensitivity responses and Th17 cell differentiation. Moreover, administration of live L. acidophilus reduced expression of four miRNAs, especially miR-146a and miR-155. In addition, the decreased expression of the miRNAs in the spleen of the L. acidophilus-treated group was closely associated with decrease of IL-17 and RORγt mRNA expression.

Complete genome sequence of bacteriocin-producing Lactobacillus plantarum KLDS1.0391, a probiotic strain with gastrointestinal tract resistance and adhesion to the intestinal epithelial cells.

Lactobacillus plantarum KLDS1.0391 is a probiotic strain isolated from the traditional fermented dairy products and identified to produce bacteriocin against Gram-positive and Gram-negative bacteria. Previous studies showed that the strain has a high resistance to gastrointestinal stress and has a high adhesion ability to the intestinal epithelial cells (Caco-2). We reported the entire genome sequence of this strain, which contains a circular 2,886,607-bp chromosome and three circular plasmids. Genes, which are related to the biosynthesis of bacteriocins, the stress resistance to gastrointestinal tract environment and adhesive performance, were identified. Whole genome sequence of Lactobacillus plantarum KLDS1.0391 will be helpful for its applications in food industry.

[Clinical Features of Pneumocystis Jiroveci Pneumonia in Patients with Inflammatory Bowel Disease].

Objective To investigate the clinical features of patients with inflammatory bowel disease (IBD) complicated with Pneumocystis Jiroveci Pneumonia (PJP). Methods We retrospectively analyzed the clinical data of 5 patients who were hospitalized in Peking Union Medical College Hospital from January 2012 to July 2017 for treatment of IBD complicated with PJP. Demographic characteristics,clinical manifestations,treatments,and outcomes were descriptively analyzed. Results Of these five patients,four had ulcerative colitis (UC) and one had Crohn's disease (CD). All patients were males,with an average age of (61.8±1.9) years. All patients were in active disease status and had symptoms including cough and suffocation. Three patients had hypoxemia,among whom two developed type 1 respiratory failure. Three patients were treated with immunosuppressive medications (corticosteroids and/or immunosuppressant drugs) before the diagnosis of PJP. Lymphocyte counts in three patients were less than 0.6×109/L. CD4+T cells in two patients were less than 200×106/L. Four patients had elevated serum cytomegalovirus DNA. The level of ß-D-glucan was elevated in four patients. Chest CT showed bilateral diffuse ground glass opacification. PJP-DNA was positive in sputum or bronchoalveolar lavage fluid in all patients. Two patients with type 1 respiratory failure required invasive mechanical ventilation. All patients received trimethoprim-sulfamethoxazole and methylprednisolone treatment. Four patients recovered completely and one died. Conclusion Elderly (aged>55 years) IBD patients who are receiving immune-suppressive therapy or with decreased peripheral blood lymphocyte count are at higher risk of PJP.

Involvement of the Hippo pathway in regeneration and fibrogenesis after ischaemic acute kidney injury: YAP is the key effector.

Renal tubule cells can recover after they undergo AKI (acute kidney injury). An incomplete repair of renal tubules can result in progressive fibrotic CKD (chronic kidney disease). Studies have revealed the relationship between tubular epithelial cells and kidney fibrogenesis. However, the underlying mechanism remains unclear. Hippo pathway components were evaluated in complete/incomplete repair of I/R (ischaemia/reperfusion) AKI rat models, HK-2 cells and AKI human renal biopsy samples. We found that the expression levels of the Hippo pathway components changed dynamically during kidney regeneration and fibrogenesis in rat models of I/R-induced AKI and human renal biopsy samples. The transcription cofactor YAP (Yes-associated protein) might be a key effector of renal regeneration and fibrogenesis. Our results showed further that YAP might elicit both beneficial and detrimental effects on I/R AKI. After I/R injury occurred, YAP could promote the repair of the injured epithelia. The constant YAP increase and activation might be related to interstitial fibrosis and abnormal renal tubule differentiation. These results indicate that the proper modulation of the Hippo pathway, specifically the transcription cofactor YAP, during repair might be a potent therapeutic target in AKI-CKD transition after I/R injury.

Identification of surface-associated proteins of Bifidobacterium animalis ssp. lactis KLDS 2.0603 by enzymatic shaving.

Bifidobacteria are commensal microorganisms of the human and animal intestinal tract, and their surface proteins can mediate bacterial communication and chemical sensing in the environment, as well as facilitate interactions between bacteria and the host. However, a systematic study of the outer surface-associated proteome of bifidobacteria has not been undertaken. In the present study, the proteins located on the surface of Bifidobacterium animalis ssp. lactis KLDS 2.0603 were systematically identified by a nongel proteomic approach, which consisted of the shaving of the bacterial surface with trypsin and an analysis of the released peptides by liquid chromatography-tandem mass spectrometry. A total of 105 surface-associated proteins were found, of which 15 proteins could potentially be involved in adhesion and interactions between bifidobacteria and the host. The proteins related to adhesion and interaction between bacteria and the host include pilus structure proteins (Fim A, Fim B), 10 moonlighting proteins, an NLP/P60 family protein, an immunogenic secreted protein, and a putative sugar-binding secreted protein. The results provide the basis for future studies on the molecular mechanisms of the interactions between bifidobacteria and the host.

Role of GATA-6 and Bone Morphogenetic Protein-2 in Dexamethasone-Induced Cleft Palate Formation in Institute of Cancer Research Mice.

The mechanism of cleft palate induction by dexamethasone is not fully known. Bone morphogenetic protein-2 (BMP-2) has been associated with dexamethasone-induced osteoporosis. In this study, the authors induced cleft palate models in Institute of Cancer Research mice by dexamethasone to investigate the role of BMP-2 and its transcriptional element GATA-6. The authors injected different doses of dexamethasone into pregnant mice (E13), and assessed the histology of the palatal shelf and the expression levels of BMP-2, GATA-6, and specific apoptosis-related proteins. The results showed that cleft palate formation was dependent on dexamethasone dosage, with high incidence (50.55%) at high concentration (50 mg/kg) compared with the low doses (6 mg/kg, 38.10%). Transmission electron microscopy revealed significant cellular changes of the cleft palate shelf, including loose cell connection, cellular swelling, as well as reduced extracellular matrix and mitochondria. Following exposure to dexamethasone, the apoptotic rate in the palate increased with elevated dosage. Western blotting analysis indicated that the expression levels of GATA-6 and BMP-2 were reduced, while the levels of apoptotic proteins bax and caspase-3 were increased. The results of authors' study suggested that dexamethasone-induced cleft palate formation involved apoptosis occurred in a dose-dependent manner. BMP-2 and GATA-6 mediated dexamethasone-induced cleft palate formation.

[Sucrose reward promotes rats' motivation for cocaine].

Caloric diet, such as fat and sugar intake, has rewarding effects, and has been indicated to affect the responses to addictive substances in animal experiments. However, the possible association between sucrose reward and the motivation for addictive drugs remains to be elucidated. Thus, we carried out behavioral tests after sucrose self-administration training to determine the effects of sucrose experience on rats' motivation for cocaine, locomotor sensitivity to cocaine, basal locomotor activity, anxiety level, and associative learning ability. The sucrose-experienced (sucrose) group exhibited higher lever press, cocaine infusion and break point, as well as upshift of cocaine dose-response curve in cocaine self-administration test, as compared with the control (chow) group. Additionally, despite similar locomotor activity in open field test and comparable score in cocaine-induced conditioned place preference, the sucrose group showed higher cocaine-induced locomotor sensitivity as compared with the chow group. The anxiety level and the performance in vocal-cue induced fear memory were similar between these two groups in elevated plus maze and fear conditioning tests, respectively. Taken together, our work indicates that sucrose experience promotes the rats' motivation for cocaine.

Investigation on reference intervals and regional differences of platelet indices in healthy Chinese Han adults.

BACKGROUND: Reference intervals are important for interpretation of clinical laboratory tests. The platelet (PLT) indices such as the mean platelet volume (MPV) and platelet distribution width (PDW) are newer hematological parameters, which have been recently reported as clinically valuable biomarkers. However, there are not many studies that have estimated the reference intervals for these parameters in healthy Chinese Han adults. OBJECTIVE: The objectives of this study were to establish reference values of PLT indices [including PLT count, MPV, PDW, platelet-large cell ratio (P-LCR), and plateletcrit (Pct)] for healthy Chinese Han adults. We also aimed to determine the region-based differences of PLT indices in China. METHODS: A total of 4,642 volunteers with a mean age of 43 were recruited from six regions of China. PLT indices were performed on Sysmex XE-2100 hematology analyzers, whose traceability was well verified. RESULTS: There were significant region-based differences for all PLT indices. Reference people in Chengdu had the lowest mean PLT count and Pct, but the highest MPV, PDW, and P-LCR among the six regions. Therefore, we derived the reference intervals in Chinese Han population excluding Chengdu reference people for PLT indices as PLT count: (127-341) × 10(9)/l; MPV: (9.20-13.30) fl; PDW: 9.90-19.00%; P-LCR: 18.10-52.00%; Pct: 16.00-41.00%. CONCLUSIONS: Region-specific reference intervals are essential as there were statistically significant region-related differences in the PLT parameters. The reference intervals established in this study differed from the existing reference values. Chengdu region may need proper specific reference ranges, which apply to their people, for all PLT parameters.

Potential antimicrobial activity of camel milk as a traditional functional food against foodborne pathogens in vivo and in vitro.

Foodborne pathogens are a leading cause of mortality worldwide. Therefore, strategies focused on functional foods are urgently required to tackle this issue. As a result, camel milk is one of the most important traditional functional foods since it contains a variety of bioactive components, which all have antimicrobial activity against foodborne pathogens. The study aims to investigate the potential antimicrobial activity of raw camel milk against foodborne pathogens in both in vitro agar well diffusion and infected mice, especially Listeria monocytogenes, Staphylococcus aureus, Salmonella Typhimurium and Escherichia coli, particularly in societies that rely on consuming camel milk in its raw form. A total of eighty C57BL/6 mice were divided into ten groups and gavaged with or without camel milk for two consecutive weeks. A blood plasma analysis and serum insulin levels were measured. Histological investigations of the liver, pancreas, kidney, spleen, lung and testicles were also performed. In both in vivo and in vitro studies when compared to other pathogenic bacteria, E. coli was the most affected by raw camel milk, with a significant clear zone of 2.9 ± 0.13 cm in vitro and in all measured parameters in vivo (p < 0.05). As a result, we advocated for further research to improve camel breeding, raise milk yield and extend its reproductive capability as one of the most important farm animals.

Intestinal lysozyme1 deficiency alters microbiota composition and impacts host metabolism through the emergence of NAD+-secreting ASTB Qing110 bacteria.

The intestine plays a pivotal role in nutrient absorption and host defense against pathogens, orchestrated in part by antimicrobial peptides secreted by Paneth cells. Among these peptides, lysozyme has multifaceted functions beyond its bactericidal activity. Here, we uncover the intricate relationship between intestinal lysozyme, the gut microbiota, and host metabolism. Lysozyme deficiency in mice led to altered body weight, energy expenditure, and substrate utilization, particularly on a high-fat diet. Interestingly, these metabolic benefits were linked to changes in the gut microbiota composition. Cohousing experiments revealed that the metabolic effects of lysozyme deficiency were microbiota-dependent. 16S rDNA sequencing highlighted differences in microbial communities, with ASTB_g (OTU60) highly enriched in lysozyme knockout mice. Subsequently, a novel bacterium, ASTB Qing110, corresponding to ASTB_g (OTU60), was isolated. Metabolomic analysis revealed that ASTB Qing110 secreted high levels of NAD+, potentially influencing host metabolism. This study sheds light on the complex interplay between intestinal lysozyme, the gut microbiota, and host metabolism, uncovering the potential role of ASTB Qing110 as a key player in modulating metabolic outcomes. IMPORTANCE: The impact of intestinal lumen lysozyme on intestinal health is complex, arising from its multifaceted interactions with the gut microbiota. Lysozyme can both mitigate and worsen certain health conditions, varying with different scenarios. This underscores the necessity of identifying the specific bacterial responses elicited by lysozyme and understanding their molecular foundations. Our research reveals that a deficiency in intestinal lysozyme1 may offer protection against diet-induced obesity by altering bacterial populations. We discovered a strain of bacterium, ASTB Qing110, which secretes NAD+ and is predominantly found in lyz1-deficient mice. Qing110 demonstrates positive effects in both C. elegans and mouse models of ataxia telangiectasia. This study sheds light on the intricate role of lysozyme in influencing intestinal health.

Clinical sequencing defines the somatic and germline mutation landscapes of Chinese HER2-Low Breast Cancer.

More than half of the breast cancer initially labeled as human epidermal growth factor receptor 2 (HER2)-negative actually exhibited low HER2 levels (IHC 1+ or IHC 2+/FISH-) and were classified as HER2-low breast cancer. Previous research emphasized the significant biological heterogeneity in HER2-low breast cancer, highlighting the importance of accurately characterizing HER2-low tumors to promote the precise management of antibody‒drug conjugates. In this study, we established a large-scale targeted sequencing cohort (N = 1907) representing Chinese HER2-low breast cancer patients with detailed clinical annotation. Our research findings revealed that HER2-low breast cancer demonstrated distinct clinical pathological characteristics and mutation landscapes compared to HER2-zero group. When compared to HER2-zero tumors, HER2-low tumors exhibited a higher proportion of Luminal B subtypes and better disease-free survival. In hormone receptor (HR)-positive breast cancer, HER2-low group showed a higher frequency of GATA3 somatic mutations, BRCA2 germline mutations, and mutations in the DNA damage repair pathway. In contrast, in HR-negative breast cancer, the HER2-low group displayed a higher frequency of PIK3CA mutations and PI3K pathway alterations. These findings offered valuable insights for the precise targeted treatment of HER2-low breast cancer in different HR statuses.

Gut dysbiosis impairs intestinal renewal and lipid absorption in Scarb2 deficiency-associated neurodegeneration.

Scavenger receptor class B, member 2 (SCARB2) is linked to Gaucher disease (GD) and Parkinson's disease (PD). Deficiency in the SCARB2 gene causes progressive myoclonus epilepsy (PME), a rare group of inherited neurodegenerative diseases characterized by myoclonus. We found that Scarb2 deficiency in mice leads to age-dependent dietary lipid malabsorption, accompanied with vitamin E deficiency. Our investigation revealed that Scarb2 deficiency is associated with gut dysbiosis and an altered bile acid pool, leading to hyperactivation of FXR in intestine. Hyperactivation of FXR impairs epithelium renewal and lipid absorption. Patients with SCARB2 mutations have a severe reduction in their vitamin E levels and cannot absorb dietary vitamin E. Finally, inhibiting FXR or supplementing vitamin E ameliorates the neuromotor impairment and neuropathy in Scarb2 knockout mice. These data indicate that gastrointestinal dysfunction is associated with SCARB2 deficiency-related neurodegeneration, and SCARB2-associated neurodegeneration can be improved by addressing the nutrition deficits and gastrointestinal issues.

Toxicity of CdTe QDs with different sizes targeted to HSA investigated by two electrochemical methods.

QDs have large scale application in many important areas with potential of unintentional exposure to the environment or organism during processing of a nanotechnology containing product's life cycle. In this paper, two classical electrochemical methods, cyclic voltammetry and electrochemical impedance spectroscopy were applied to investigate the influence of particle sizes of CdTe QDs on their toxicity targeted to human serum albumin (HSA) under simulative physiological conditions. The results show that the toxicity of yellow emitting QDs (YQDs) on HSA is slightly stronger than that of the green-emitting (GQDs) and red-emitting QDs (RQDs). We also compared these two classical electrochemical methods with the traditional fluorescence spectroscopy through the above results. The electrochemical methods may be more accurate and comprehensive to investigate the toxicity of QDs at the biomacromolecular level under certain conditions, though fluorescence spectroscopy is simpler and more sensitive.