Effectiveness of a standardized quality control management procedure for COVID-19 RT-PCR testing: a large-scale diagnostic accuracy study in China.

BACKGROUND: The study aimed to construct a standardized quality control management procedure (QCMP) and access its accuracy in the quality control of COVID-19 reverse transcriptase-polymerase chain reaction (RT-PCR). METHODS: Considering the initial RT-PCR results without applying QCMP as the gold standard, a large-scale diagnostic accuracy study including 4,385,925 participants at three COVID-19 RT-PCR testing sites in China, Foshan (as a pilot test), Guangzhou and Shenyang (as validation sites), was conducted from May 21, 2021, to December 15, 2022. RESULTS: In the pilot test, the RT-PCR with QCMP had a high accuracy of 99.18% with 100% specificity, 100% positive predictive value (PPV), and 99.17% negative predictive value (NPV). The rate of retesting was reduced from 1.98% to 1.16%. Its accuracy was then consistently validated in Guangzhou and Shenyang. CONCLUSIONS: The RT-PCR with QCMP showed excellent accuracy in identifying true negative COVID-19 and relieved the labor and time spent on retesting.

[Cadmium Phytoremediation Effect of Sweet Sorghum Assisted with Citric Acid on Typical Parent Soil in Southern China].

Sweet sorghum has a large biomass and strong cadmium (Cd) absorption capacity, which has the potential for phytoremediation of Cd-contaminated soil. In order to study the Cd phytoremediation effect of sweet sorghum assisted with citric acid on the typical parent materials in southern China, a field experiment was carried out in two typical parent material farmland areas (neutral purple mud field and jute sand mud field) with Cd pollution in Hunan Province. The results showed that:① Citric acid had no inhibitory effect on the growth of sweet sorghum. After the application of citric acid, the aboveground biomass of sweet sorghum at the maturity stage increased by 10.1%-24.7%. ② Both sweet sorghum planting and citric acid application reduced the soil pH value, and the application of citric acid further reduced the soil pH value at each growth stage of sweet sorghum; this decrease was greater in the neutral purple mud field, which decreased by 0.24-0.72 units. ③ Both sweet sorghum planting and citric acid application reduced the total amount of soil Cd, and the decreases in the neutral purple mud field and jute sand mud field were 23.8%-52.2% and 17.1%-31.8%, respectively. The acid-extractable percentage of soil Cd in both places increased by 38.6%-147.7% and 4.8%-22.7%, respectively. ④ The application of citric acid could significantly increase the Cd content in various tissues of sweet sorghum. The Cd content in the aboveground part of the plant in the neutral purple mud field was higher than that in the jute sand mud field, and the Cd content in stems and leaves was 0.25-1.90 mg·kg-1 and 0.21-0.64 mg·kg-1, respectively. ⑤ After applying citric acid, the Cd extraction amount of sweet sorghum in neutral purple mud soil in the mature stage reached 47.56 g·hm-2. In summary, citric acid could enhance the efficiency of sweet sorghum in the phytoremediation of Cd-contaminated soil, and the effect was better in neutral purple mud fields. This technology has the potential for remediation coupled with agro-production for heavy metal-contaminated farmland.

Advancing glioblastoma treatment by targeting metabolism.

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.

Physicochemical properties of a novel chestnut porous starch nanoparticle.

A novel chestnut porous starch nanoparticle (PSNP) was successfully synthesized, combining the properties of starch nanoparticle (SNP) and porous starch. The SNP obtained through ultrasonic and acid hydrolysis, exhibited a smaller particle size (173.9 nm) and a higher specific surface area (SSA) compared to native starch. After the synergistic hydrolysis by α-amylase and glucoamylase, the porous structure appeared on the surface of SNP. The prepared PSNP had a size of 286.3 nm and the highest SSA. In the adsorption experiments, PSNP showed higher capacities for adsorbing water, oil and methylene blue (MB) compared to other samples. The acid and enzymatic treatments resulted in a decrease in the levels of total starch content and amylose ratio. Furthermore, the treatments increased the levels of relative crystallinity (RC) and solubility, while decreasing the short-range ordered structure and swelling ratio at high temperatures. It was observed that the SSA of starch granules positively correlated with the MB and water adsorption capacity (WAC), solubility, and RC. These findings highlight the potential of the novel PSNP as an efficient adsorbent for bioactive substances and dyes.

Core microbiota for nutrient digestion remained and ammonia utilization increased after continuous batch culture of rumen microbiota in vitro.

Introduction: This study aimed to investigate the digestive function, urea utilization ability, and bacterial composition changes in rumen microbiota under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro. Methods: The gas production, dry matter digestibility, and bacterial counts were determined for the continuously batch-cultured rumen fluid (CRF). The changes in fermentation parameters, NH3-N utilization efficiency, and microbial taxa were analyzed in CRF and were compared with that of fresh rumen fluid (RF), frozen rumen fluid (FRF, frozen rumen fluid at -80°C for 1 month), and the mixed rumen fluid (MRF, 3/4 RF mixed with 1/4 CRF) with in vitro rumen fermentation. Results: The results showed that the dry matter digestibility remained stable while both the microbial counts and diversity significantly decreased over the 23 days of continuous batch culture. However, the NH3-N utilization efficiency of the CRF group was significantly higher than that of RF, FRF, and MRF groups (p < 0.05), while five core genera including Succinivibrio, Prevotella, Streptococcus, F082, and Megasphaera were retained after 23 days of continuous batch culture. The NH3-N utilization efficiency was effectively improved after continuous batch culture in vitro, and Streptococcus, Succinivibrio, Clostridium_sensu_stricto_1, p.251.o5, Oxalobacter, Bacteroidales_UCG.001, and p.1088.a5_gut_group were identified to explain 75.72% of the variation in NH3-N utilization efficiency with the RandomForest model. Conclusion: Thus, core bacterial composition and function retained under high urea (5% urea in diet) over 23 days of continuous batch culture in vitro, and bacterial biomarkers for ammonia utilization were illustrated in this study. These findings might provide potential applications in improving the efficiency and safety of non-protein nitrogen utilization in ruminants.

Prediction of positive pulmonary nodules based on machine learning algorithm combined with central carbon metabolism data.

BACKGROUND: Lung cancer causes a huge disease burden, and early detection of positive pulmonary nodules (PPNs) as an early sign of lung cancer is extremely important for effective intervention. It is necessary to develop PPNs risk recognizer based on machine learning algorithm combined with central carbon metabolomics. METHODS: The study included 2248 participants at high risk for lung cancer from the Ma'anshan Community Lung Cancer Screening cohort. The Least Absolute Shrinkage and Selection Operator (LASSO) was used to screen 18 central carbon-related metabolites in plasma, recursive feature elimination (RFE) was used to select all 42 features, followed by five machine learning algorithms for model development. The performance of the model was evaluated using area under the receiver operator characteristic curve (AUC), accuracy, precision, recall, and F1 scores. In addition, SHapley Additive exPlanations (SHAP) was performed to assess the interpretability of the final selected model and to gain insight into the impact of features on the predicted results. RESULTS: Finally, the two prediction models based on the random forest (RF) algorithm performed best, with AUC values of 0.87 and 0.83, respectively, better than other models. We found that homogentisic acid, fumaric acid, maleic acid, hippuric acid, gluconic acid, and succinic acid played a significant role in both PPNs prediction model and NPNs vs PPNs model, while 2-oxadipic acid only played a role in the former model and phosphopyruvate only played a role in the NPNs vs PPNs model. This model demonstrates the potential of central carbon metabolism for PPNs risk prediction and identification. CONCLUSION: We developed a series of predictive models for PPNs, which can help in the early detection of PPNs and thus reduce the risk of lung cancer.

Non-Contact Current Sensing System Based on the Giant Magnetoimpedance Effect of CoFeNiSiB Amorphous Ribbon Meanders.

A sensitive non-contact sensing system based on the CoFeNiSiB amorphous ribbon giant magnetoimpedance (GMI) effect is proposed for current testing. The sensing system consists of a GMI probe, a sinusoidal current generator, a voltage follower, a preamplifier, a low-pass filter, and a peak detector. Four different GMI probes derived from amorphous ribbon meanders are designed and fabricated through MEMS processes. GMI probes were driven by a 10 MHz, 5 mA AC current. A permanent magnet was used to provide a bias magnetic field for the probe. The effect of the bias magnetic field on the output DC voltage was investigated. This non-contact current sensing system exhibits good sensitivity and linearity at a bias magnetic field Hbias = 15 Oe. The sensitivity can reach up to 24.2 mV/A in the ±1.5 A range.

MicroRNA-204-5p Ameliorates Renal Injury via Regulating Keap1/Nrf2 Pathway in Diabetic Kidney Disease.

Background: Diabetic kidney disease (DKD) is characterized by renal fibrosis, and the pathogenesis of renal fibrosis is still not definitely confirmed. MiR-204-5p plays an important role in the regulation of fibrosis, autophagy and oxidative stress. In this study, we aimed to investigate the role of miR-204-5p on renal damage in diabetic kidneys and the underlying mechanisms involved. Methods: In vivo, AAV-Ksp-miR-204-5p mimics were injected into mice via tail vein. In vitro, high glucose-induced HK-2 cells were treated with miR-204-5p inhibitor, miR-204-5p mimics, ATG5 siRNA, tertiary butyl hydroquinone (TBHQ), ML385, or 3-Methyladenine (3-MA). FISH and qRT-PCR were used to detect miR-204-5p expression. The expressions of protein and mRNA were detected by Western blotting, immunofluorescence, immunohistochemistry and qRT-PCR. The concentration of fibronectin in HK-2 cells culture medium was detected by ELISA. Results: The expression of miR-204-5p in diabetic kidneys was significantly inhibited than that in control group. Delivering miR-204-5p mimics increased miR-204-5p expression, improved renal function, inhibited renal fibrosis and oxidative stress, and restored autophagy in db/db mice. In vitro, the expression of miR-204-5p was inhibited by HG treatment in HK-2 cells. MiR-204-5p mimics effectively increased miR-204-5p expression and reduced fibronectin and collagen I expression, restored autophagy dysfunction, and increased Nrf2 expression, whereas these alterations were abrogated by Nrf2 inhibitor ML385, autophagy inhibitor 3-methyladenine (3-MA, 5 mM) treatment or ATG5 siRNA transfection in HG-induced HK-2 cells. In addition, miR-204-5p inhibitor significantly inhibited miR-204-5p expression and aggravated HG-induced fibronectin and collagen I expression, autophagy dysfunction, and decreased Nrf2 expression, while these alterations were abolished by Nrf2 activator TBHQ. Furthermore, the binding of miR-204-5p with Keap1 was confirmed by luciferase reporter assay and miR-204-5p negatively regulated Keap1 expression, resulting in the activation of Nrf2 pathway. Conclusion: MicroRNA-204-5p protects against the progression of diabetic renal fibrosis by restoring autophagy via regulating Keap1/Nrf2 pathway.

Galectin-3 aggravates microglial activation and tau transmission in tauopathy.

Alzheimer's disease is characterized by the accumulation of amyloid-ß plaques, aggregation of hyperphosphorylated tau (pTau), and microglia activation. Galectin-3 (Gal3) is a ß-galactoside-binding protein that has been implicated in amyloid pathology. Its role in tauopathy remains enigmatic. Here, we showed that Gal3 was upregulated in the microglia of humans and mice with tauopathy. pTau triggered the release of Gal3 from human induced pluripotent stem cell-derived microglia in both its free and extracellular vesicular-associated (EV-associated) forms. Both forms of Gal3 increased the accumulation of pathogenic tau in recipient cells. Binding of Gal3 to pTau greatly enhanced tau fibrillation. Besides Gal3, pTau was sorted into EVs for transmission. Moreover, pTau markedly enhanced the number of EVs released by iMGL in a Gal3-dependent manner, suggesting a role of Gal3 in biogenesis of EVs. Single-cell RNA-Seq analysis of the hippocampus of a mouse model of tauopathy (THY-Tau22) revealed a group of pathogenic tau-evoked, Gal3-associated microglia with altered cellular machineries implicated in neurodegeneration, including enhanced immune and inflammatory responses. Genetic removal of Gal3 in THY-Tau22 mice suppressed microglia activation, reduced the level of pTau and synaptic loss in neurons, and rescued memory impairment. Collectively, Gal3 is a potential therapeutic target for tauopathy.

Cand2 inhibits CRL-mediated ubiquitination and suppresses autophagy to facilitate pathogenicity of phytopathogenic fungi.

The ubiquitin-proteasome system and the autophagy system are the two primary mechanisms used by eukaryotes to maintain protein homeostasis, and both are closely related to the pathogenicity of the rice blast fungus. In this research, we identified MoCand2 as an inhibitor of ubiquitination in Magnaporthe oryzae. Through this role, MoCand2 participates in the regulation of autophagy and pathogenicity. Specifically, we found that deletion of MoCand2 increased the ubiquitination level in M. oryzae, whereas overexpression of MoCand2 inhibited the accumulation of ubiquitinated proteins. Interaction analyses showed that MoCand2 is a subunit of Cullin-RING ligases (CRLs). It suppresses ubiquitination by blocking the assembly of CRLs and downregulating the expression of key CRL subunits. Further research indicated that MoCand2 regulates autophagy through ubiquitination. MoCand2 knockout led to over-ubiquitination and over-degradation of MoTor, and we confirmed that MoTor content was negatively correlated with autophagy level. In addition, MoCand2 knockout accelerated the K63 ubiquitination of MoAtg6 and strengthened the assembly and activity of the phosphatidylinositol-3-kinase class 3 complex, thus enhancing autophagy. Abnormal ubiquitination and autophagy in ΔMocand2 resulted in defects in growth, conidiation, stress resistance, and pathogenicity. Finally, sequence alignment and functional analyses in other phytopathogenic fungi confirmed the high conservation of fungal Cand2s. Our research thus reveals a novel mechanism by which ubiquitination regulates autophagy and pathogenicity in phytopathogenic fungi.

Physiological tolerance of black locust (Robinia pseudoacacia L.) and changes of rhizospheric bacterial communities in response to Cd and Pb in the contaminated soil.

Woody plants possess great potential for phytoremediation of heavy metal-contaminated soil. A pot trial was conducted to study growth, physiological response, and Cd and Pb uptake and distribution in black locust (Robinia pseudoacacia L.), as well as the rhizosphere bacterial communities in Cd and Pb co-contaminated soil. The results showed that R. pseudoacacia L. had strong physiological regulation ability in response to Cd and Pb stress in contaminated soil. The total chlorophyll, malondialdehyde (MDA), soluble protein, and sulfhydryl contents, as well as antioxidant enzymes (superoxide dismutase, peroxidase, catalase) activities in R. pseudoacacia L. leaves under the 40 mg·kg-1 Cd and 1000 mg·kg-1 Pb co-contaminated soil were slightly altered. Cd uptake in R. pseudoacacia L. roots and stems increased, while the Pb content in the shoots of R. pseudoacacia L. under the combined Cd and Pb treatments decreased in relative to that in the single Pb treatments. The bacterial α-diversity indices (e.g., Sobs, Shannon, Simpson, Ace, and Chao) of R. pseudoacacia L. rhizosphere soil under Cd and Pb stress were changed slightly relative to the CK treatment. However, Cd and Pb stress could significantly (p < 0.05) alter the rhizosphere soil microbial communities. According to heat map and LEfSe (Linear discriminant analysis Effect Size) analysis, Bacillus, Sphingomonas, Terrabacter, Roseiflexaceae, Paenibacillus, and Myxococcaceae at the genus level were notably (p < 0.05) accumulated in the Cd- and/or Pb-contaminated soil. Furthermore, the MDA content was notably (p < 0.05) negatively correlated with the relative abundances of Isosphaeraceae, Gaiellales, and Gemmatimonas. The total biomass of R. pseudoacacia L. was positively (p < 0.05) correlated with the relative abundances of Xanthobacteraceae and Vicinamibacreraceae. Network analysis showed that Cd and Pb combined stress might enhance the modularization of bacterial networks in the R. pseudoacacia L. rhizosphere soil. Thus, the assembly of the soil bacterial communities in R. pseudoacacia L. rhizosphere may improve the tolerance of plants in response to Cd and/or Pb stress.

Engineering the Relatively Conserved Residues in Active Site Architecture of Thermophilic Chitinase SsChi18A Enhanced Catalytic Activity.

Chitinase plays a vital role in the efficient biotransformation of the chitin substrate. This study aimed to modify and elucidate the contribution of the relatively conserved residues in the active site architecture of a thermophilic chitinase SsChi18A from Streptomyces sp. F-3 in processive catalysis. The enzymatic activity on colloidal chitin increased to 151%, 135%, and 129% in variants Y286W, E287A, and K186A compared with the wild type (WT). Also, the apparent processive parameter G2/G1 was lower in the variants compared to the WT, indicating the essential role of Tyr-286, Glu-287, and Lys-186 in processive catalysis. Additionally, the enzymatic activity on the crystalline chitin of F48W and double mutants F48W/Y209F and F48W/Y286W increased by 35%, 16%, and 36% compared with that for WT. Molecular dynamics simulations revealed that the driving force of processive catalysis might be related to the changes in interaction energy. This study provided a rational design strategy targeting relatively conserved residues to enhance the catalytic activity of GH18 processive chitinases.

Targeted metabolomics reveals the association between central carbon metabolism and pulmonary nodules.

With the widespread application of low-dose computed tomography (LDCT) technology, pulmonary nodules have aroused more attention. Significant alteration in plasma metabolite levels, mainly amino acid and lipid, have been observed in patients of PNs. However, evidence on the association between central carbon metabolism and PNs are largely unknown. The aim of this study was to investigate the underlying association of PNs and plasma central carbon metabolites. We measured the levels of 16 plasma central carbon metabolites in 1954 participants who gained LDCT screening in MALSC cohort. The inverse probability weighting (IPW) technique was used to control for bias due to self-selection for LDCT in the assessed high-risk population. The least absolute shrinkage and selection operator (LASSO) penalized regression was used to deal with the problem of multicollinearity among metabolites and the combined association of central carbon metabolites with PNs was estimated by using quantile g-computation (QgC) models. A quartile increase in 3-hydroxybutyric acid, gluconic acid, succinic acid and hippuric acid was positively associated with the PNs risk, whereas a quartile increase in 2-oxadipic acid and fumaric acid was negatively associated with the risk of PNs in multiple-metabolite models. A positive but insignificant joint associations of the mixture of 16 metabolites with PNs was observed by using QgC models analyses. Further studies are warranted to clarify the association between circulating metabolites and PNs and the biological mechanisms.

Integrated metabolome and transcriptome analyses of anthocyanin biosynthesis reveal key candidate genes involved in colour variation of Scutellaria baicalensis flowers.

BACKGROUND: Bright flower colour assists plants attract insects to complete pollination and provides distinct ornamental values. In some medicinal plants, diverse flower colour variations usually imply differences in active ingredients. Compared to the common bluish purple of Scutellaria baicalensis flower (SB), the natural variants present rose red (SR) and white (SW) flowers were screened out under the same growing conditions in the genuine producing area Shandong Province, China. However, the mechanism of flower colour variation in S. baicalensis was remain unclear. In the present study, we conducted integrated transcriptome and metabolome analyses to uncover the metabolic difference and regulation mechanism in three S. baicalensis flowers. RESULTS: The results showed that 9 anthocyanins were identified. Among which, 4 delphinidin-based anthocyanins were only detected in SB, 4 cyanidin-based anthocyanins (without cyanidin-3-O-glucoside) mainly accumulated in SR, and no anthocyanin but high level of flavanone, naringenin, was detected in SW. The gene expression profile indicated that the key structural genes in the flavonoid and anthocyanin biosynthesis pathway differentially expressed in flowers with different colours. Compared to SB, the down-regulated expression of F3'5'H, ANS, and 3GT gene in SR might influence the anthocyanin composition. Especially the InDel site with deletion of 7 nucleotides (AATAGAG) in F3'5'H in SR might be the determinant for lack of delphinidin-based anthocyanins in rose red flowers. In SW, the lower expression levels of DFR and two F3H genes might reduce the anthocyanin accumulation. Notably the SNP site of G > A mutation in the splicing site of DFR in SW might block anthocyanin biosynthesis from flavanones and thus cause white flowers. In addition, several key transcription factors, including MYB, bHLH, and NAC, which highly correlated with structural gene expression and anthocyanin contents were also identified. CONCLUSIONS: These results provide clues to uncover the molecular regulatory mechanism of flower colour variation in S. baicalensis and promote novel insights into understanding the anthocyanin biosynthesis and regulation.

3D-US and CBCT Dual-guided Radiotherapy for Postoperative Uterine Malignancy: A Primary Workflow Set-up.

Introduction: The consistency of clinical target volume is essential to guiding radiotherapy with precision for postoperative uterine malignancy patients. By introducing a three-dimensional ultrasound system (3D-US) into image-guided radiation therapy (IGRT), this study was designed to investigate the initial workflow set-up, the therapeutic potential, and the adverse events of 3D-US and cone-beam computed tomography (CBCT) dual-guided radiotherapy in postoperative uterine malignancy treatment. Methods: From April 2021 to December 2021, postoperative uterine malignancy patients were instructed to follow the previously standard protocol of daily radiation treatment, particularly a 3D-US (Clarity system) guiding was involved before CBCT. Soft-tissue-based displacements resulting from the additional US-IGRT were acquired in the LT (left)/RT (right), ANT (anterior)/POST (posterior), and SUP (superior)/INF(inferior) directions of the patient before fractional treatment. Displacement distributions before and after treatment either from 3D-US or from CBCT were also estimated and compared subsequently, and the urinary and rectal toxicity was further evaluated. Results: All the patients completed radiation treatment as planned. The assessment of 170 scans resulted in a mean displacement of (0.17 ± 0.24) cm, (0.19 ± 0.23) cm, (0.22 ± 0.26) cm for bladder in LT/RT, ANT/POST, and SUP/INF directions. A mean deviation of (0.26 ± 0.22) cm, (0.58 ± 0.5) cm, and (0.3 ± 0.23) cm was also observed for the bladder centroid between the CBCT and computed tomography -simulation images in three directions. Paired comparison between these two guidance shows that the variations from 3D-US are much smaller than those from CBCT in three directions, especially in ANT/POST and SUP/INF directions with significance (P = 0.000, 0.001, respectively). During treatment, and 0, 3, 6, 9, and 12 months after treatment, there was no severe urinary and rectal toxicity happened. Conclusion: A primary workflow of 3D-US and CBCT dual-guided radiotherapy has been established, which showed great therapeutic potential with mild to moderate urinary and rectal toxicity for postoperative uterine malignancy patients. But the clinical outcomes of this non-invasive technique need to be investigated further.

Effective Degradation of Brewer Spent Grains by a Novel Thermostable GH10 Xylanase.

Brewer spent grains (BSGs) are one of the most abundant by-products in brewing industry. Due to microbiological instability and high perishability, the efficient degradation of BSGs is of environmental and economic importance. Streptomyces sp. F-3 could grow in the medium with BSGs as the only carbon and nitrogen source. Proteome mass spectrometry revealed that a GH10 xylanase SsXyn10A could be secreted in large quantities. SsXyn10A showed optimum activity at pH 7.0 and 60 °C. SsXyn10A exhibited excellent thermostability which retained approximately 100% and 58% after incubation for 5 h at 50 and 60 °C. SsXyn10A displayed high activity to beechwood xylan (BX) and wheat arabinoxylan (WAX). SsXyn10A is active against xylotetracose (X4), xylopentose (X5), and xylohexose (X6) to produce main products xylobiose (X2) and xylotriose (X3). Ssxyn10A showed synergistic effects with commercial cellulase on BSGs hydrolyzing into soluble sugar. In addition, the steam explosion pretreatment of BSGs as the substrate produced twice as much reducing sugar as the degradation of the original substrate. This study will contribute to efficient utilization of BSGs and provide a thermostable GH10 xylanase which has potential application in biomass hydrolysis.

Association analysis of BclI with benign lymphoepithelial lesions of the lacrimal gland and glucocorticoids resistance.

AIM: To evaluate the relationship between gene polymorphism (BclI, ER22/23EK, N363S) and the occurrence, progression and sensitivity to glucocorticoid of lacrimal gland benign lymphoepithelial lesion (LGBLEL). METHODS: Clinical peripheral blood samples of 52 LGBLEL patients and 10 normal volunteers were collected for DNA extraction and polymerase chain reaction sequencing to analyze single nucleotide polymorphism (SNP) genotypes. The lacrimal tissues of LGBLEL were surgically removed and made into paraffin sections for subsequent hematoxylin-eosin (HE) and Masson staining analysis. The duration of disease and hormone use of LGBLEL patients from diagnosis to surgery were also analyzed. The Meta-analysis follows PRISMA guidelines to conducted a systematic review of human studies investigating the relationship between the NR3C1 BclI polymorphism and glucocorticoids (GCs) sensitivity. RESULTS: There was no association between ER22/23EK or N363S and the occurrence of LGBLEL or GCs sensitivity (P>0.05); BclI GC genotype was closely related to GCs resistance (P=0.03) as is the minor allele C (P=0.0017). The HE staining and Masson staining showed that the GC genotype of BclI remarkably slowed down the disease progression and reduced fibrosis (P<0.05), especially for GCs-dependent patients (P<0.0001). Meta-analysis showed that BclI was not significantly associated with GCs responsiveness. CONCLUSION: The LGBLEL patients who carry the NR3C1 BclI allele C may be more sensitive to GCs and associated with lower fibrosis and slower disease progression. The results may guide the clinical treatment strategy for the LGBLEL patients.

Comparison of magnetoimpedance behaviors in meander CoFeNiSiB amorphous ribbon for deformation sensing applications.

In this work, micro-ribbon strips and meanders based on CoFeNiSiB amorphous ribbons were fabricated by using the lithography technique and chemical etching. Flat and curved holders with different radius of curvature were obtained via 3D printing techniques for GMI testing. Longitudinal and transverse GMI (LGMI and TGMI) behaviors of micro-ribbon sensors in different bending directions and degrees were systematically investigated. The results show the LGMI and TGMI effects of micro-ribbon meanders with one turn is most sensitive to bending. It can be used in the development of deformation sensors. In addition, there is a linear range of field in the LGMI and TGMI curves of micro ribbons under different bending conditions, and the sensitivity of micro-ribbon sensors shows no significant change in the range. In particular, the micro-ribbon meanders with three turns are the least sensitive to bending deformation and can be used to develop stable and flexible GMI sensors for wearable electronics devices.

Mitochondria: one of the vital hubs for molecular hydrogen's biological functions.

As a novel antioxidant, a growing body of studies has documented the diverse biological effects of molecular hydrogen (H2) in a wide range of organisms, spanning animals, plants, and microorganisms. Although several possible mechanisms have been proposed, they cannot fully explain the extensive biological effects of H2. Mitochondria, known for ATP production, also play crucial roles in diverse cellular functions, including Ca2+ signaling, regulation of reactive oxygen species (ROS) generation, apoptosis, proliferation, and lipid transport, while their dysfunction is implicated in a broad spectrum of diseases, including cardiovascular disorders, neurodegenerative conditions, metabolic disorders, and cancer. This review aims to 1) summarize the experimental evidence on the impact of H2 on mitochondrial function; 2) provide an overview of the mitochondrial pathways underlying the biological effects of H2, and 3) discuss H2 metabolism in eukaryotic organisms and its relationship with mitochondria. Moreover, based on previous findings, this review proposes that H2 may regulate mitochondrial quality control through diverse pathways in response to varying degrees of mitochondrial damage. By combining the existing research evidence with an evolutionary perspective, this review emphasizes the potential hydrogenase activity in mitochondria of higher plants and animals. Finally, this review also addresses potential issues in the current mechanistic study and offers insights into future research directions, aiming to provide a reference for future studies on the mechanisms underlying the action of H2.

SRSF2 is required for mRNA splicing during spermatogenesis.

BACKGROUND: RNA splicing plays significant roles in fundamental biological activities. However, our knowledge about the roles of alternative splicing and underlying mechanisms during spermatogenesis is limited. RESULTS: Here, we report that Serine/arginine-rich splicing factor 2 (SRSF2), also known as SC35, plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf2 by Stra8-Cre caused complete infertility and defective spermatogenesis. Further analyses revealed that deletion of Srsf2 disrupted differentiation and meiosis initiation of spermatogonia. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF2 regulatory networks play critical roles in several major events including reproductive development, spermatogenesis, meiotic cell cycle, synapse organization, DNA recombination, chromosome segregation, and male sex differentiation. Furthermore, SRSF2 affected expression and alternative splicing of Stra8, Stag3 and Atr encoding critical factors for spermatogenesis in a direct manner. CONCLUSIONS: Taken together, our results demonstrate that SRSF2 has important functions in spermatogenesis and male fertility by regulating alternative splicing.