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Abstract Objective We aimed to analyze the relationship between non-alcoholic fatty liver and progressive fibrosis and serum 25-hydroxy vitamin D (25(OH)D) in patients with type 2 diabetes mellitus. Methods A total of 184 patients with T2DM who were hospitalized in the Department of Endocrinology of the ShiDong Clinical Hospital between January 2023 and June 2023 were selected. We compared review of anthropometric, biochemical, and inflammatory parameters and non-invasive scores between groups defined by ultrasound NAFLD severity grades.We determine the correlation between 25(OH)D and FLI and FIB-4 scores, respectively. Results Statistically significant differences were seen between BMI, WC, C-peptide levels, FPG, ALT, serum 25(OH)D, TC, HDL, lumbar spine bone density, FLI, and FIB-4 in different degrees of NAFLD. Multivariate logistic regression analysis showed that 25(OH)D (OR = 1.26, p = 0.001), age (OR = 0.93, P

Abstract Salvia miltiorrhiza is commonly used as a Chinese herbal medicine to treat different cardiovascular and cerebrovascular illnesses due to its active ingredients. Environmental conditions, especially drought stress, can affect the yield and quality of S. miltiorrhiza. However, moderate drought stress could improve the quality of S. miltiorrhiza without significantly reducing the yield, and the mechanism of this initial drought resistance is still unclear. In our study, transcriptome and metabolome analyses of S. miltiorrhiza under different drought treatment groups (CK, A, B, and C groups) were conducted to reveal the basis for its drought tolerance. We discovered that the leaves of S. miltiorrhiza under different drought treatment groups had no obvious shrinkage, and the malondialdehyde (MDA) contents as well as superoxide dismutase (SOD) and peroxidase (POD) activities dramatically increased, indicating that our drought treatment methods were moderate, and the leaves of S. miltiorrhiza began to initiate drought resistance. The morphology of root tissue had no significant change under different drought treatment groups, and the contents of four tanshinones significantly enhanced. In all, 5213, 6611, and 5241 differentially expressed genes (DEGs) were shared in the A, B, and C groups compared with the CK group, respectively. The results of KEGG and co-expression analysis showed that the DEGs involved in plant-pathogen interactions, the MAPK signaling pathway, phenylpropanoid biosynthesis, flavonoid biosynthesis, and plant hormone signal transduction responded to drought stress and were strongly correlated with tanshinone biosynthesis. Furthermore, the results of metabolism analysis indicated that 67, 72, and 92 differentially accumulated metabolites (DAMs), including fumarate, ferulic acid, xanthohumol, and phytocassanes, which were primarily involved in phenylpropanoid biosynthesis, flavonoid biosynthesis, and diterpenoid biosynthesis pathways, were detected in these groups. These discoveries provide valuable information on the molecular mechanisms by which S. miltiorrhiza responds to drought stress and will facilitate the development of drought-resistant and high-quality S. miltiorrhiza production.

Abstract Background Venom systems are ideal models to study genetic regulatory mechanisms that underpin evolutionary novelty. Snake venom glands are thought to share a common origin, but there are major distinctions between venom toxins from the medically significant snake families Elapidae and Viperidae, and toxin gene regulatory investigations in elapid snakes have been limited. Here, we used high-throughput RNA-sequencing to profile gene expression and microRNAs between active (milked) and resting (unmilked) venom glands in an elapid (Eastern Brown Snake, Pseudonaja textilis), in addition to comparative genomics, to identify cis- and trans-acting regulation of venom production in an elapid in comparison to viperids (Crotalus viridis and C. tigris). Results Although there is conservation in high-level mechanistic pathways regulating venom production (unfolded protein response, Notch signaling and cholesterol homeostasis), there are differences in the regulation of histone methylation enzymes, transcription factors, and microRNAs in venom glands from these two snake families. Histone methyltransferases and transcription factor (TF) specificity protein 1 (Sp1) were highly upregulated in the milked elapid venom gland in comparison to the viperids, whereas nuclear factor I (NFI) TFs were upregulated after viperid venom milking. Sp1 and NFI cis-regulatory elements were common to toxin gene promoter regions, but many unique elements were also present between elapid and viperid toxins. The presence of Sp1 binding sites across multiple elapid toxin gene promoter regions that have been experimentally determined to regulate expression, in addition to upregulation of Sp1 after venom milking, suggests this transcription factor is involved in elapid toxin expression. microRNA profiles were distinctive between milked and unmilked venom glands for both snake families, and microRNAs were predicted to target a diversity of toxin transcripts in the elapid P. textilis venom gland, but only snake venom metalloproteinase transcripts in the viperid C. viridis venom gland. These results suggest differences in toxin gene posttranscriptional regulation between the elapid P. textilis and viperid C. viridis. Conclusions Our comparative transcriptomic and genomic analyses between toxin genes and isoforms in elapid and viperid snakes suggests independent toxin regulation between these two snake families, demonstrating multiple different regulatory mechanisms underpin a venomous phenotype.

Abstract Background Toxoplasma gondii is an important protozoan pathogen with medical and veterinary importance worldwide. Drugs currently used for treatment of toxoplasmosis are less effective and sometimes cause serious side effects. There is an urgent need for the development of more effective drugs with relatively low toxicity. Methods The effect of tylosin on the viability of host cells was measured using CCK8 assays. To assess the inhibition of tylosin on T. gondii proliferation, a real-time PCR targeting the B1 gene was developed for T. gondii detection and quantification. Total RNA was extracted from parasites treated with tylosin and then subjected to transcriptome analysis by RNA sequencing (RNA-seq). Finally, murine infection models of toxoplasmosis were used to evaluate the protective efficacy of tylosin against T. gondii virulent RH strain or avirulent ME49 strain. Results We found that tylosin displayed low host toxicity, and its 50% inhibitory concentration was 175.3 μM. Tylsoin also inhibited intracellular T. gondii tachyzoite proliferation, with a 50% effective concentration of 9.759 μM. Transcriptome analysis showed that tylosin remarkably perturbed the gene expression of T. gondii, and genes involved in “ribosome biogenesis (GO:0042254)” and “ribosome (GO:0005840)” were significantly dys-regulated. In a murine model, tylosin treatment alone (100 mg/kg, i.p.) or in combination with sulfadiazine sodium (200 mg/kg, i.g.) significantly prolonged the survival time and raised the survival rate of animals infected with T. gondii virulent RH or avirulent ME49 strain. Meanwhile, treatment with tylosin significantly decreased the parasite burdens in multiple organs and decreased the spleen index of mice with acute toxoplasmosis. Conclusions Our findings suggest that tylosin exhibited potency against T. gondii both in vitro and in vivo, which offers promise for treatment of human toxoplasmosis. Graphical Abstract

Abstract Electroencephalography (EEG) is a non-invasive measurement method for brain activity. Due to its safety, high resolution, and hypersensitivity to dynamic changes in brain neural signals, EEG has aroused much interest in scientific research and medical fields. This article reviews the types of EEG signals, multiple EEG signal analysis methods, and the application of relevant methods in the neuroscience field and for diagnosing neurological diseases. First, three types of EEG signals, including time-invariant EEG, accurate event-related EEG, and random event-related EEG, are introduced. Second, five main directions for the methods of EEG analysis, including power spectrum analysis, time–frequency analysis, connectivity analysis, source localization methods, and machine learning methods, are described in the main section, along with different sub-methods and effect evaluations for solving the same problem. Finally, the application scenarios of different EEG analysis methods are emphasized, and the advantages and disadvantages of similar methods are distinguished. This article is expected to assist researchers in selecting suitable EEG analysis methods based on their research objectives, provide references for subsequent research, and summarize current issues and prospects for the future.

Abstract Objective In the treatment of resectable pancreatic cancer, adjuvant chemotherapy is viewed as essential. However, it is yet unclear how well adjuvant chemotherapy works at different illness stages. This study aims to investigate the efficacy of adjuvant chemotherapy in various pancreatic cancer stages. Materials and methods Patients with pancreatic cancer who underwent surgical intervention at Sun Yat-sen University Cancer Center between January 2018 and January 2021 were included in this retrospective analysis. Results 168 patients were divided into two groups: the group receiving adjuvant chemotherapy (AC) and the group receiving independent surgery (no-AC). Survival analysis reveals that among stage I patients, the AC group demonstrates significant superiority over the no-AC group in terms of recurrence-free survival (RFS) and overall survival (OS) (P = 0.0028; P = 0.022). While there was no discernible difference in RFS between the AC and no-AC groups for patients with stage II illness (P = 0.69), the AC group significantly outperformed the no-AC group in terms of OS (P = 0.047). There was no discernible difference in RFS or OS between the AC and no-AC groups for patients with stage III pancreatic cancer (P = 0.40 and P = 0.20, respectively). Conclusions The administration of adjuvant chemotherapy has been shown to improve the prognosis of patients diagnosed with stage I and II pancreatic cancer. However, its efficacy is limited in individuals with stage III pancreatic cancer. Therefore, there is an urgent need to investigate and develop more effective therapeutic options for patients in the advanced stage.

Abstract Aim To provide a systematic review of the qualitative literature on self‐reported barriers to self‐management in pregnant women with gestational diabetes mellitus (GDM). Design Systematic review. Methods This systematic review followed the Joanna Briggs Institute meta‐aggregation approach and was evaluated using the Joanna Briggs Institute Critical Appraisal Checklist for Qualitative Research. Qualitative studies on the barriers to self‐management among GDM pregnancy survivors conducted until 17 May 2022, were searched. Results A total of 30 studies were included, of which seven were in Chinese and 23 were in English, and 10 findings resulted in three themes: (a) Knowledge and belief, (b) Skills and abilities and (c) Environment and social support. By summarizing the self‐reported barriers to self‐management in patients with GDM and recommends precise interventions for these barriers, thereby saving health resources and helping to increase their willingness and ability to engage in self‐management.

Objective: To develop a novel diagnostic modality to identify and diagnose stroke in daily life scenarios for improving the therapeutic effects and prognoses of patients. Methods: In this study, 16 stroke patients and 24 age-matched healthy participants as controls were recruited for comparative analysis. Leveraging a portable eye-tracking device and integrating traditional Chinese medicine theory with modern color psychology principles, we recorded the eye movement signals and calculated eye movement features. Meanwhile, the stroke recognition models based on eye movement features were further trained by using random forest (RF), k-nearest neighbors (KNN), decision tree (DT), gradient boosting classifier (GBC), XGBoost, and CatBoost. Results: The stroke group and the healthy group showed significant differences in some eye movement features (P

Many different chicken breeds are found around the world, their features vary among them, and they are valuable resources. Currently, there is a huge lack of knowledge of the genetic determinants responsible for phenotypic and biochemical properties of these breeds of chickens. Understanding the underlying genetic mechanisms that explain across-breed variation can help breeders develop improved chicken breeds. The whole-genomes of 140 chickens from 7 Shandong native breeds and 20 introduced recessive white chickens from China were re-sequenced. Comparative population genomics based on autosomal single nucleotide polymorphisms (SNPs) revealed geographically based clusters among the chickens. Through genome-wide scans for selective sweeps, we identified thyroid stimulating hormone receptor (TSHR, reproductive traits, circadian rhythm), erythrocyte membrane protein band 4.1 like 1 (EPB41L1, body size), and alkylglycerol monooxygenase (AGMO, aggressive behavior), as major candidate breed-specific determining genes in chickens. In addition, we used a machine learning classification model to predict chicken breeds based on the SNPs significantly associated with recourse characteristics, and the prediction accuracy was 92%, which can effectively achieve the breed identification of Laiwu Black chickens. We provide the first comprehensive genomic data of the Shandong indigenous chickens. Our analyses revealed phylogeographic patterns among the Shandong indigenous chickens and candidate genes that potentially contribute to breed-specific traits of the chickens. In addition, we developed a machine learning-based prediction model using SNP data to identify chicken breeds. The genetic basis of indigenous chicken breeds revealed in this study is useful to better understand the mechanisms underlying the resource characteristics of chicken.

Clinical presentation of central nervous system (CNS) infections caused by varicella-zoster virus (VZV) is highly sophisticated, making identification challenging. We retrospectively reported 18 cases of VZV neurologic disease confirmed by metagenomic next-generation sequencing (mNGS). The detection rate of mNGS was higher than that of PCR assay (100 vs 66.7%, p < 0.05) and serum IgM antibody (100 vs 68.8%, p < 0.05) measurement. Of the 18 cases, five patients were diagnosed with acute meningitis, three with acute meningitis combined with facial neuritis, three with acute meningitis combined with polycranial neuritis, and the remaining seven with various clinical diagnoses. Typical clinical symptoms included headache (15), fever (9), and rash (11). Cranial or spinal MRI showed abnormalities in 12 patients, and 17 patients had obvious neurological symptoms. The predominant genotype of VZV in this study was genotype J (100%, 10/10). All patients were treated with acyclovir/penciclovir and dexamethasone, 16 recovered and 2 died. Our study highlights the good performance of mNGS in diagnosing CNS infection caused by VZV. It could provide additional diagnostic evidence in patients with diverse clinical spectrum and variable manifestations.

Shrinkage cracks are some of the most common defects in timber structures obtained from woods with an uneven distribution of moisture content and are subject to external dynamic environmental changes. To accurately predict the changes in the moisture content of wood components at any time and position, this study first applied the principles of food drying and established a moisture field model for laminated wood based on the analogy between heat and humidity transfer. A model for predicting the moisture content of wood that considers time and spatial distribution was then proposed. Second, by collecting relevant experimental data and establishing a finite element analysis model, three moisture absorption conditions (0–9.95%, 0–13.65%, and 0–17.91%) and four desorption conditions (34–5.5%, 28–8.3%, 31–11.8%, and 25.5–15.9%) were analyzed. In the moisture absorption comparison, the time needed to reach 95% equilibrium moisture content was 2.43 days, 4.07 days, and 6.32 days. The rate at which the internal components reached equilibrium moisture content exceeded 10 days. The temporal and spatial distribution of wood moisture content revealed the correctness of the proposed wood moisture field model. Finally, the moisture content prediction model was applied in the order of characteristic equation solutions, moisture content gradient difference, and laminated wood size. The results revealed that the established humidity field model can predict the wood moisture content and how it changes over time and in space. Notably, 1–2 orders for the solution of the characteristic equation are recommended when applying the prediction model. The greater the difference in moisture content, the faster the equilibrium moisture content is reached. The moisture content varies greatly based on the component size and position. Notably, the influence of moisture gradient and wood size on the average wood moisture content cannot be ignored.

Arbuscular mycorrhizal (AM) fungi can establish a mutualistic relationship with the roots of most terrestrial plants to increase plant nutrient uptake. The effects of potassium uptake and transport by AM symbiosis are much less reported compared to other nutrients. In this research, a heterologous yeast system was used to verify that the LbHAK has capacity for potassium uptake. The split-roots system implemented using seedlings of Lycium barbarum confirmed that R. irregularis locally induced LbHAK expression, which means that LbHAK is only expressed in mycorrhizal roots. Furthermore, the impacts of overexpression of LbHAK on the growth, nutrients and water uptake, and transport of mycorrhizal tobacco (inoculation with Rhizophagus irregularis) at 0.2 mM and 2 mM K conditions were assessed. The mycorrhizal tobacco growth and potassium accumulation were significantly enhanced through LbHAK overexpression in tobacco. In addition, overexpression of LbHAK substantially enhanced phosphorus content, while stimulating the expression of NtPT4, Rir-AQP1, and Rir-AQP2 in mycorrhizal tobacco. Moreover, LbHAK overexpression greatly promoted AM colonization. LbHAK has a potential role in facilitating potassium absorption through the mycorrhizal pathway, and overexpression of LbHAK in tobacco may promote the transport of potassium, phosphorus, and water from AM fungi to tobacco. These data imply the important roles played by the LbHAK in AM-fungi-induced potassium uptake in L. barbarum and in improving plant nutrients and AM colonization.

As a renewable resource, cellulose has the advantages of wide source, environmental friendliness, biodegradability and biocompatibility. It is found that emulsions prepared with solid particles as stabilizers have higher stability than traditional surfactant-stabilized emulsions, and cellulose is an excellent stabilizer for Pickering emulsions due to its biocompatibility, wide source and environmental friendliness and has a broad prospect for application as a natural dietary fiber in the food field. In this article, the characteristics of Pickering emulsions stabilized by different kinds of cellulose and the different properties different treatments impart to nanocellulose-stabilized Pickering emulsions are reviewed. The recent applications of nanocellulose-based emulsions in the food field such as preparation of food-grade polymer materials, preparation of new low-calorie foods, delivery of bioactive substances and auxiliary digestion are described, which can provide a reference for broadening the application of cellulose-based Pickering emulsions.

Background Skeletal muscle mass is an essential parameter for diagnosing sarcopenia. The gold standard for assessing skeletal muscle mass is using computed tomography (CT) to measure skeletal muscle area at the third lumbar vertebra (L3) level. This study aims to investigate whether skeletal muscle mass could be evaluated at the first lumbar vertebra (L1) level using images obtained from routine chest CT scans. Methods Skeletal muscle index (SMI, cm2/m2) and skeletal muscle density (SMD, HU) are commonly used to measure relative muscle mass and the degree of fat infiltration. This study used CT images at the L1 level to measure the skeletal muscle area (SMA, cm2) in 815 subjects from the health examination center. Linear regression analysis was used to explore the association between L1 and L3 measurements. The receiver operating characteristic (ROC) analysis was used to assess the predictive performance of L1 SMI for sarcopenia. The sex-specific cut-off values for low skeletal muscle mass in patients under the age of 60 were determined using the following formula: “mean − 1.28 × standard deviation.” A multivariate linear regression model was established. Results A significantly higher SMI at the L1 level was found in males than in females (43.88 ± 6.33 cm2/m2 vs 33.68 ± 5.03 cm2/m2; P < 0.001). There were strong correlations between measures at the L1 and L3 levels in both the total subject and sex-specific analyses. A negative association was found between age and L3 SMI in males (r = −0.231, P = 0.038). Both body mass index (BMI) and body surface area (BSA) were positively associated with L1 SMI in both males and females. A multivariate analysis was used to establish a prediction rule to predict SMI at the L3 level. The assessment of consistency and interchangeability between predicted and actual SMI at the L3 level yielded moderately good results. Considering the significant differences observed between male and female participants, the sex-specific cut-off values of the L1 SMI for defining low skeletal muscle mass were 36.52 cm2/m2 in males and 27.29 cm2/m2 in females. Conclusions Based on a population from central China, the correlated indicators obtained at the L1 level from routine chest CT scans may serve as effective surrogate markers for those at the L3 level in assessing overall skeletal muscle mass.

ObjectiveTo predict the incidence trend of influenza-like illness proportion （ILI%） in Shanghai using the seasonal autoregressive integrated moving average model （SARIMA）， and to provide an important reference for timely prevention and control measures.MethodsTime series analysis was performed on ILI% surveillance data of Shanghai Municipal Center for Disease Control and Prevention from the 15th week of 2015 to the 52nd week of 2019， and a prediction model was established. Seasonal autoregressive integrated moving average （SARIMA） model was established using data from the foregoing 212 weeks， and prediction effect of the model was evaluated using data from the latter 36 weeks.ResultsFrom the 15th week of 2015 to the 52nd week of 2019， the average ILI% in Shanghai was 1.494%， showing an obvious epidemic peak. SARIMA（1，0，0） （2，0，0） 52 was finally modeled. The residual of the model was white noise sequence， and the true values were all within the 95% confidence interval of the predicted values.ConclusionSARIMA（1，0，0） （2，0，0） 52 can be used for the medium term prediction of ILI% in Shanghai， and can play an early warning role for the epidemic and outbreak of influenza in Shanghai.

Sensory nerves are important for tissue homeostasis. Here the authors show that sensory nerves contribute to Mesenchymal stem cell maintenance via FGF1, mTOR signaling and autophagy.

Abstract Intense ultraviolet (UV) exposure can cause phototoxic reactions, such as skin inflammation, resulting in injury. UV is a direct cause of DNA damage, but the mechanisms underlying transcriptional regulation within cells after DNA damage are unclear. The bioinformatics analysis of transcriptome sequencing data from UV‐irradiated and non‐UV‐irradiated skin showed that transcription‐related proteins, such as HSF4 and COIL, mediate cellular response to UV irradiation. HSF4 and COIL can form a complex under UV irradiation, and the preference for binding target genes changed because of the presence of a large number of R‐loops in cells under UV irradiation and the ability of COIL to recognize R‐loops. The regulation of target genes was altered by the HSF4–COIL complex, and the expression of inflammation and ageing‐related genes, such as Atg7, Tfpi, and Lims1, was enhanced. A drug screen was performed for the recognition sites of COIL and R‐loop. N6‐(2‐hydroxyethyl)‐adenosine can competitively bind COIL and inhibit the binding of COIL to the R‐loop. Thus, the activation of downstream inflammation‐related genes and inflammatory skin injury was inhibited.

Reactivation of latent human herpesvirus 2 (HHV-2) can cause spontaneous recovering aseptic meningitis and recurrent meningitis in adults, but it rarely affects the brain parenchyma to cause encephalitis. Here, we report the case of a 37-year-old male patient admitted to our hospital due to fever with a progressive headache for 3 days and paroxysmal episodes of unconsciousness for 1 day. Brain magnetic resonance imaging (MRI) revealed viral meningoencephalitis. Then, metagenomics next-generation sequencing (mNGS) was applied, which detected 12,024 unique sequences of HHV-2 in cerebrospinal fluid (2022), indicating HHV-2 encephalitis. After antiviral treatment, the patient’s symptoms improved, and he was discharged. During the 1-month follow-up, the patient recovered without any new symptoms, but a brain MRI revealed significant atrophy of the original foci. The patient was finally diagnosed with HHV-2 necrotizing meningoencephalitis, which is extremely rare. mNGS helped with the clinical diagnosis and strengthened our understanding of HHV-2 infections in the central nervous system.

It remains a huge challenge for clinicians to diagnose Pneumocystis jirovecii pneumonia (PJP) by a conventional method, which leads to delay in diagnosing PJP, accounting for higher mortality in patients with rheumatoid arthritis (RA). A 69-year-old woman, who suffered from RA for years, developed acute respiratory failure. The computed tomography scan showed diffused effusion and ground glass opacity in both lungs, which could not be differentiated from interstitial pneumonia. Metagenomic next-generation sequencing (mNGS) revealed P. jirovecii in both serum and bronchoalveolar lavage fluid with reads per million (RPM) of 17 and 437, while other diagnostic tests did not detect any pathogenic microorganism. The results were verified by quantitative polymerase chain reaction (mtSSU region) against the same samples. The DNA RPM of P. jirovecii declined notably after treatment with trimethoprim/sulfamethoxazole. The patient was discharged without treatment and finally passed away. This case fully highlights the sensitivity of mNGS in early diagnosis of PJP, which is of great significance for prognosis and treatment. Nonetheless, the clinical application of mNGS is worth further standardization and normalization.

Potassium plays important roles in most plant physiological processes. Arbuscular mycorrhizal (AM) fungi promote plant water and mineral nutrient acquisition to promote plant growth. However, few studies have focused on the effect of AM colonization on potassium uptake by the host plant. In this study, the effects of an AM fungus (Rhizophagus irregularis) and potassium concentration (0, 3, or 10 mM K+) on Lycium barbarum were evaluated. A split-root test with L. barbarum seedlings was conducted, and the potassium uptake capacity of LbKAT3 was verified in yeast. A tobacco line overexpressing LbKAT3 was generated and mycorrhizal functions under two potassium concentrations (0.2 and 2 mM K+) were studied. Inoculation of R. irregularis and application of potassium increased the dry weight, and potassium and phosphorus contents of L. barbarum, and increased the colonization rate and arbuscule abundance of R. irregularis. In addition, the expression of LbKAT3 and AQP genes in L. barbarum was upregulated. Inoculation of R. irregularis induced LbPT4, Rir-AQP1, and Rir-AQP2 expression, and application of potassium upregulated the expression of these genes. Inoculation with the AM fungus locally regulated the expression of LbKAT3. Inoculation of R. irregularis improved the growth, and potassium and phosphorus contents, and induced NtPT4, Rir-AQP1, and Rir-AQP2 expression in tobacco overexpressing LbKAT3 under both potassium concentrations. Overexpression of LbKAT3 in tobacco improved the growth, potassium accumulation, and AM colonization, and upregulated the expression of NtPT4 and Rir-AQP1 in mycorrhizal tobacco. The results suggest that LbKAT3 may assist in mycorrhizal potassium uptake, and overexpression of LbKAT3 may promote potassium, phosphorus, and water transport from the AM fungus to tobacco.

Background: The efficacy of therapy in cervical cancer (CESC) is blocked by high molecular heterogeneity. Thus, the sub-molecular characterization remains primarily explored for personalizing the treatment of CESC patients. Methods: Datasets with 741 CESC patients were obtained from TCGA and GEO databases. The NMF algorithm, random forest algorithm, and multivariate Cox analysis were utilized to construct a classifier for defining the sub-molecular characterization. Then, the biological characteristics, genomic variations, prognosis, and immune landscape in molecular subtypes were explored. The significance of classifier genes was validated by quantitative Real-Time PCR, cell transfection, cell colony formation assay, wound healing assay, cell proliferation assay, and Western blot. Results: The CESC patients were classified into two subtypes, and the high classifier-score patients with significant differences in ECM-receptor interaction, PI3K-Akt signaling pathway, and MAPK signaling pathway showed a poorer prognosis in OS (p

Hypervirulent Klebsiella pneumoniae (hvKp) causes increasing infections in healthy individuals from the community. In severe cases, it can cause multiple organ infection with invasive metastasis of blood sources, seriously threatening the patients’ life. Rapid and accurate diagnosis of the pathogen becomes the key to timely antibiotic treatment to improve the prognosis. This article reports a case of liver abscess complicated with multiple organ invasive infection caused by hematogenous-disseminated hvKp. K. pneumoniae was identified by culture and metagenomic next-generation sequencing (mNGS) using blood and liver abscess drainage fluid. The isolates from the two samples were subsequently identified with high homology (99.999%) by whole genome sequencing. In addition, multiple virulence genes were detected in the two isolates and the string test was positive, indicating hvKp with hypermucoviscosity phenotype. Multiple antibiotic treatments were given. The conditions of the patient were stable but the temperature remained high. Surgical drainage treatment was performed, and the patient’s body temperature immediately dropped to normal. He finally recovered after 6 months of follow-up. mNGS using body fluids can facilitate the rapid diagnosis of pathogens. For hvKp infection, choosing a better antibiotic therapy and receiving surgical drainage can significantly improve the prognosis of the patient.

Shrinkage cracks severely affect the safety of wood structures. Therefore, the moisture stress distribution of shrinkage cracks should be analyzed, and the interface crack depth of wood components predicted. In this paper, the equilibrium conditions, physical conditions, geometric conditions, and coordination equations of the disk humidity stress under a moisture content gradient Δw are deduced by referring to the elastic analytical solution model of temperature stress. Moreover, the humidity stress distribution equation is established, which is verified via the finite element method. The critical water content and shrinkage crack depth prediction models are further deduced based on the humidity stress distribution. The usability of the model is further verified using the test data of actual engineered wood components. The results demonstrate that the moisture stress is not determined by the initial moisture content Wi, equilibrium moisture content We, or member size but by moisture content gradient Δw. The shrinkage crack prediction model of wood components in cross-section can be applied to actual engineering prediction to provide a theoretical basis for the reinforcement measures and safety evaluation of wood structures.

Grain sorghum has been a significant contributor to global food security since the prehistoric period and may contribute even more to the security of both food and energy in the future. Globally, precise management techniques are crucial for increasing grain sorghum productivity. In China, with diverse ecological types, variety introduction occasionally occurs across ecological zones. However, few information is available on the effect of ecological type on genotype performance and how plant spacing configuration influences grain yield in various ecological zones. Hence, a series of two-year field experiments were conducted in 2020 and 2021 in four ecological zones of China, from the northeast to the southwest. The experiments included six widely adapted sorghum varieties under six plant spacing configurations (two row spacing modes: equidistant row spacing (60 cm) mode and wide (80 cm)-narrow (40 cm) row spacing mode; three in-row plant spacings: 10 cm, 15 cm, and 20 cm). Our results indicated that ecological type, variety, and plant spacing configuration had a significant effect on sorghum yield. Ecological type contributed the highest proportion to the yield variance (49.8%), followed by variety (8.3%), while plant spacing configuration contributed 1.8%. Sorghum growth duration was highly influenced by the ecological type, accounting for 87.2% of its total variance, whereas plant height was mainly affected by genotype, which contributed 81.6% of the total variance. All test varieties, developed in the south or north, can reach maturity within 94-108 d, just before fall sowing in central China. Generally, sorghum growth duration becomes longer when a variety is introduced from south to north. A late-maturing variety, developed in the spring sowing and late-maturing regions, possibly could not reach maturity in the early-maturing region. The row spacing modes had no significant affect on sorghum yield, but the equal-row spacing mode consistently caused higher yields with only one exception; this might imply that equal-row spacing mode was more advantageous for boosting sorghum yield potential. In contrast, decreasing in-row plant spacing showed significant positive linear associations with sorghum grain yield in most cases. In addition, these results demonstrated that sorghum is a widely adapted crop and enables success in variety introduction across ecological zones.

Abstract Evidences indicate that elevated levels of circulating ErbB2 are closely associated with increased incidence of diabetes. However, the relationship between ErbB2 concentration and glycemic variations (GV) in type 2 diabetic (T2D) patients remains elucidated. The aim of this study was to assess whether there is an association between serum ErbB2 concentration and GV in newly diagnosed T2D patients. This was a three-center, and observational study. Between April 2019 and July 2019, a total of 106 newly diagnosed T2D patients were recruited. All recruited subjects were admitted as inpatients and received anti-diabetes agents free during the study period. At baseline, fasting serum was collected for ErbB2 measurement and all recruited patients were subjected a prospective CGM for at least 3 days. The primary endpoint was the relationships between ErbB2 concentrations and GV in T2D patients. Data of a total of 95 subjects who met the inclusion criteria were analyzed at the endpoint. Subjects were divided into quartiles according to their serum ErbB2 concentrations. We observed that subjects with an elevated level of ErbB2 had a higher value of GV in terms of mean amplitude of glucose excursion (MAGE), standard deviation of mean glucose (SDMG), and the coefficient of variation (CV%) than those with lower levels (all P

The communication between myogenic cells and their surrounding connective tissues is indispensable for muscle morphogenesis. During late embryonic development in mice, myogenic progenitors migrate to discrete sites to form individual muscles. The detailed mechanism of this process remains unclear. Using mouse levator veli palatini (LVP) development as a model, we systematically investigated how a distinct connective tissue subpopulation, perimysial fibroblasts, communicates with myogenic cells to regulate mouse pharyngeal myogenesis. Using single-cell RNAseq data analysis, we identified that TGF-β signaling is a key regulator for the perimysial fibroblasts. Loss of TGF-β signaling in the neural crest-derived palatal mesenchyme leads to defects in perimysial fibroblasts and muscle malformation in the soft palate in Osr2Cre;Tgfbr1fl/fl mice. In particular, Creb5, a transcription factor expressed in the perimysial fibroblasts, cooperates with TGF-β signaling to activate expression of Fgf18. Moreover, Fgf18 supports pharyngeal muscle development in vivo and exogenous Fgf18 can partially rescue myogenic cell numbers in Osr2Cre;Tgfbr1fl/fl samples, illustrating that TGF-β-regulated Fgf18 signaling is required for LVP development. Collectively, our findings reveal the mechanism by which TGF-β signaling achieves its functional specificity in defining the perimysial-to-myogenic signals for pharyngeal myogenesis.

Sorghum [Sorghum bicolor (L.) Moench] is an important crop for food security in semiarid and arid regions due to its high tolerance to abiotic and biotic stresses and its good performance in marginal lands with relatively low fertility. To deeply understand the interrelationship among sorghum genotype, environment, sowing dates, and densities in the spring sowing early maturing (SSEM) areas of China, and to provide a basis for specifying scientific and reasonable cultural practices, a two-year field experiment was conducted with six popular varieties at six locations. Combined ANOVA showed that the yield difference between years was significant (P

Generation of reactive oxygen species (ROS) are possibly induced by the crosstalk between mitochondria and endoplasmic reticula, which is physiologically important in apoptosis. Cytochrome c (Cyt c) is believed to play a crucial role in such signaling pathway by interrupting the coupling within microsomal monooxygenase (MMO). In this study, the correlation of ROS production with the electron transfer between Cyt c and the MMO system is investigated by resonance Raman (RR) spectroscopy. Binding of Cyt c to MMO is found to induce the production of ROS, which is quantitatively determined by the in-situ RR spectroscopy reflecting the interactions of Cyt c with generated ROS. The amount of ROS that is produced from isolated endoplasmic reticulum depends on the redox state of the Cyt c, indicating the important role of oxidized Cyt c in accelerating apoptosis. The role of electron transfer from MMO to Cyt c in the apoptotic mitochondria-endoplasmic reticulum pathway is accordingly proposed. This study is of significance for a deeper understanding of how Cyt c regulates apoptotic pathways through the endoplasmic reticulum, and thus may provide a rational basis for the design of antitumor drugs for cancer therapy.

ObjectiveGestational diabetes mellitus (GDM) has been linked to subsequent overall cardiovascular diseases. However, evidence on the associations of GDM with type-specific cardiovascular diseases is lacking, and findings on the potential impact of type 2 diabetes on the associations are not consistent. This study aimed to explore the associations between GDM and the risks of type-specific cardiovascular diseases.MethodsData were from 12,025 women (≥20 years) who had delivered at least one live birth in the National Health and Nutrition Examination Survey, 2007–2018. GDM history and type-specific cardiovascular diseases including coronary heart disease (CHD), heart failure and stroke were defined by self-report. We also combined our results with those from previously related publications on the associations between GDM and risks of type-specific cardiovascular diseases with a random-effect model.ResultsCompared with women without GDM, the multivariable-adjusted odds ratios (95% confidence intervals) were 1.82 (1.21–2.72) for CHD, 1.43 (0.80–2.53) for heart failure, and 1.19 (0.76–1.86) for stroke among women with a history of GDM. Type 2 diabetes was associated with 43.90, 67.44, and 63.16% of the excess odds of CHD, heart failure and stroke associated with GDM, respectively. Combining results from this study with those from previously related studies yielded odds ratios (95% confidence intervals) of 1.81 (1.60–2.05) for CHD (12 studies, 7,615,322 participants, I2= 72.6%), 1.66 (1.25–2.21) for heart failure (5 studies, 4,491,665 participants, I2= 88.6%), and 1.25 (1.07–1.46) for cerebrovascular disease (9 studies, 6,090,848 participants, I2= 77.8%).ConclusionsGDM showed stronger associations with coronary heart diseases and heart failure than cerebrovascular disease, and the excess risks are attributable, in part, to type 2 diabetes.

Primary amoebic meningoencephalitis (PAM) caused by Naegleria fowleri is a fatal infection with a mortality rate of more than 95%, despite advances in antimicrobial chemotherapy and supportive care. Initial manifestations of PAM are indistinguishable from bacterial meningitis. Prompt diagnosis and antifungal treatment may help decline the overall mortality. Here we present a case of a 38-year-old man transferred to our hospital due to mild headache, which deteriorated quickly. Severe increased intracranial pressure was found. The cerebrospinal fluid (CSF) was yellowish with significantly increased leukocyte and protein. Smear and culture were negative. The patient was first diagnosed with pyogenic meningoencephalitis. However, the symptoms deteriorated. Metagenomic next-generation sequencing (mNGS) of CSF was applied and finally confirmed N. fowleri as the protist pathogen within 24 h. However, due to the time cost of sampling and transportation (2 days), the diagnosis came too late, and the patient passed away 1 day before. In summary, mNGS is a rapid and accurate diagnostic method for clinical practices, especially for rare central nervous system infections. It should be used as quickly as possible for acute infections, such as PAM. All aspects of patient interrogation and prompt identification should be paramount to ensure appropriate treatment and decline the overall mortality.

Secreted immunoglobulin A (SIgA), IgG, and IgM play a crucial role in forming the intestinal mucosal immune barrier, and parasites could disturb the host's immune response by releasing various immunomodulatory molecules. Moniezia benedeni is an important pathogen parasitizing in the sheep small intestine. It is aimed to explore the residence characteristics of IgA+, IgG+, and IgM+ cells in the sheep small intestine, and the influence of Moniezia benedeni infection on them. Control group (n = 6) and infected group (n = 6) were selected, respectively, and the three subtype cells residing in the small intestine were systematically observed and analyzed. The results showed that in the Control group, the three types of positive cells were all distributed diffusely, and the total densities in jejunum, duodenum and ileum was gradually declined in turn. Notably, the change trend of IgA+ and IgG+ cells densities were both congruent with the total densities, and the differences among them were significant, respectively (P < 0.05); the IgM+ cells density was the highest in duodenum, followed by jejunum and ileum, there was no significant difference between duodenum and jejunum (P > 0.05), but both significantly higher than in ileum (P < 0.05). In the Infected group, their total densities in duodenum, jejunum and ileum were gradually declined in turn. Notably, the IgA+ and IgM+ cells densities change trend was the same as the total densities, and the differences among them were significant, respectively (P < 0.05). The IgG+ cells density in duodenum was the highest, followed by ileum and jejunum and there was significantly difference among them (P < 0.05). The comparison results between Control and Infected groups showed that from the duodenum, jejunum to ileum, IgA+, IgG+, and IgM+ cells were all reduced significantly, respectively. The results suggest that the three types of positive cells were resided heterogeneously in the small intestinal mucosa, that is, significant region-specificity; Moniezia benedeni infection could not change their diffuse distribution characteristics, but strikingly, reduce their resident densities, and the forming mucosal immune barrier were significantly inhibited. It provided powerful evidence for studying on the molecular mechanism of Moniezia benedeni evasion from immune surveillance by strongly inhibiting the host's mucosal immune barrier.

Abstract The column, which is the vertical main structural part of the building, bears the force transmitted from the upper beam and slab and is a crucial part of the structure. In this study, the columns with a rectangular section cut from poplar were reinforced by basalt fiber-reinforced polymer (BFRP) strips with four different reinforced configurations. The mechanical behaviors of the specimens were also investigated under different eccentricities. Experimental results are presented as follows: for the wooden columns under axial compression, the wooden column BFRP with one layer spaced apart, two layers spaced apart, one layer fully filled, and two layers fully reinforced demonstrated increased bearing capacities of 3.13%, 30.00%, 40.63%, and 65.00%, respectively; the longitudinal strain increased by 7.54%, 19.65%, 22.06%, and 30.69%, and the lateral strain decreased by 26.53%, 29.80%, 41.30%, and 66.64%, respectively. Meanwhile, for the wooden column subjected to eccentric compression, the bearing capacities of the aforementioned wooden column BFRP configurations increased by 8.70%, 19.56%, 23.91%, and 30.43%; the longitudinal strain of the wooden column increased by 25.41%, 35.20%, 39.52%, and 41.85%; and the transverse strain increased by 130.77%, 166.77%, 192.57%, and 230.86%. In addition, the finite element model was used to simulate the eccentric compression behavior of the specimen. However, the ultimate bearing capacity and deflection of the analyzed column were higher than the test value. This finding was due to the completely ideal state of poplar in Finite Element Analysis (FEA) modeling without the influence of some initial defects, such as knots. These values can roughly be used as a reference for experimental results for the repair and reinforcement of poplar structures in Xinjiang.

Whether metagenomic next-generation sequencing (mNGS) could benefit patients with suspected severe central nervous system (CNS) infection in terms of diagnosis and antibiotic treatment remains unknown. We retrospectively analyzed 79 patients with suspected CNS infection and undertook mNGS. The value of mNGS was investigated in terms of identification of pathogen and guidance for the adjustment of antibiotic treatment. The relationship between the time of initiating mNGS since onset and the Glasgow Outcome Scale (GOS) score after 90-day follow-up were analyzed. Fifty out of 79 cases with suspicious severe CNS infection were finally diagnosed. Despite previous routine laboratory tests, mNGS further promoted the accurate identification of pathogens in 23 cases (47.9%). The sensitivity, specificity, and accuracy of mNGS test in this study were 84.0, 79.3, and 82.3%, respectively. Furthermore, mNGS facilitated the adjustment of empirical antibiotic treatments in 38 cases (48.1%). The time of taking mNGS since onset had an insignificant weak positive correlation with GOS after 90-day follow-up (r = −0.73, P = 0.08). mNGS facilitated the accurate identification of pathogens in suspicious severe CNS infections and promoted the accurate antibiotic therapy even empirical antibiotics were administrated. It should be taken as early as possible to improve the clinical outcome of patients with suspicious severe CNS infection.

Syringa reticulata subsp. amurensis (Rupr.) P. S. Green & M. C. Chang (Oleaceae) is a shrub or tree with high medicinal value as well as great ecological significance as an urban garden plant. To better understand the molecular genetics and evolutionary of S. reticulata subsp. amurensis, its complete chloroplast genome was sequenced and annotated. The assembled chloroplast genome is a circular 156,141 bp sequence, consisting of 87,108 bp large single copy (LSC) region and 17,239 bp small single copy (SSC) region, which were flanked by a pair of 25,897 bp inverted repeats (IRs). The GC content of the chloroplast genome is 36.14%. Moreover, a total of 132 functional genes were annotated, including 88 protein-coding, 36 tRNA, and eight rRNA genes. Phylogenetic analysis showed that S. reticulata subsp. amurensis was most closely related to S. reticulata subsp. Pekinensis and the genus Syringa is paraphyletic group. This study provides important information for further phylogenetic studies on S. reticulata subsp. amurensis and its allies.

Abstract. Mitochondrial injury and endoplasmic reticulum (ER) stress are considered to be the key mechanisms of renal ischemia-reperfusion (I/R) injury. Mitochondria are membrane-bound organelles that form close physical contact with a specific domain of the ER, known as mitochondrial-associated membranes. The close physical contact between them is mainly restrained by ER-mitochondria tethering complexes, which can play an important role in mitochondrial damage, ER stress, lipid homeostasis, and cell death. Several ER-mitochondria tethering complex components are involved in the process of renal I/R injury. A better understanding of the physical and functional interaction between ER and mitochondria is helpful to further clarify the mechanism of renal I/R injury and provide potential therapeutic targets. In this review, we aim to describe the structure of the tethering complex and elucidate its pivotal role in renal I/R injury by summarizing its role in many important mechanisms, such as mitophagy, mitochondrial fission, mitochondrial fusion, apoptosis and necrosis, ER stress, mitochondrial substance transport, and lipid metabolism.

Epigenetic regulation plays extensive roles in diseases and development. Disruption of epigenetic regulation not only increases the risk of cancer, but can also cause various developmental defects. However, the question of how epigenetic changes lead to tissue-specific responses during neural crest fate determination and differentiation remains understudied. Using palatogenesis as a model, we reveal the functional significance of Kdm6b, an H3K27me3 demethylase, in regulating mouse embryonic development. Our study shows that Kdm6b plays an essential role in cranial neural crest development, and loss of Kdm6b disturbs P53 pathway-mediated activity, leading to complete cleft palate along with cell proliferation and differentiation defects in mice. Furthermore, activity of H3K27me3 on the promoter of Trp53 is antagonistically controlled by Kdm6b, and Ezh2 in cranial neural crest cells. More importantly, without Kdm6b, the transcription factor TFDP1, which normally binds to the promoter of Trp53, cannot activate Trp53 expression in palatal mesenchymal cells. Furthermore, the function of Kdm6b in activating Trp53 in these cells cannot be compensated for by the closely related histone demethylase Kdm6a. Collectively, our results highlight the important role of the epigenetic regulator KDM6B and how it specifically interacts with TFDP1 to achieve its functional specificity in regulating Trp53 expression, and further provide mechanistic insights into the epigenetic regulatory network during organogenesis.

7A04 aluminum alloy has high strength and strong corrosion resistance, and its quality is only 1/3 of steel. Using 7A04 aluminum alloy to replace ordinary steel tube to confined concrete, it can effectively reduce the member section, reduce the weight of the structure, and more in line with the material requirements of large span materials and high-rise buildings. In this paper, nine groups of 7A04 aluminum alloy tube confined high strength concrete long column were tested under axial compression and eccentric compression with aspect ratio and eccentricity as variables. And the corresponding ABAQUS finite element model was established. The results show that the failure phenomena of the nine groups are basically the same, and the specimen deflection curve shape is similar to the sine half-wave curve. The ultimate bearing capacity of the specimen decreases with the increase of aspect ratio and eccentricity. When the axial compression or eccentricity of the specimen is small, the variation of the longitudinal and transverse strain at the midspan is similar in the elastic stage. When the eccentricity is large, the longitudinal and transverse strain at the midspan of the specimen is obviously tensile at one side and compressive at one side at the beginning. Finally, based on the test and simulation results, a formula for calculating the bearing capacity of 7A04 aluminum alloy tube high strength concrete long columns is proposed. This formula can better predict the stable bearing capacity of the specimen, which has certain reference significance for the structural design of 7A04 aluminum alloy tube high strength concrete long columns.

The application of tube-filled concrete composite columns is becoming more and more popular. The traditional tube-filled column is easy to rust and expensive to maintain, which leads to the practical need of replacing high-strength aluminum alloy. 7A04 aluminum alloy has high strength and strong corrosion resistance, which is more in line with the material requirements of modern building structures. In view of this, four groups of 7A04 aluminum alloy tube concrete short columns were tested under axial compression, and the corresponding ABAQUS finite element simulation was established. The influence of tube thickness and concrete strength grade on compressive strength, ductility, transverse deformation coefficient, and improvement coefficient of strong concrete strength of composite column is considered in this paper. The results show that the failure mode of composite short columns is central uplift or shear failure. The tube thickness of high-strength aluminum tube has a great influence on the strength of specimens, and the ductility of composite columns decreases with the decrease of the collar coefficient. The finite element model can well reflect the development trend of the load-strain curve, and the formula of composite column bearing capacity proposed by regression analysis can well predict the strength of 7A04 aluminum alloy tubular concrete short column. The research results have a certain reference significance for the structural design of high strength aluminum concrete-filled columns.

Abstract Poplar plants with peculiar characteristics grow extensively and naturally in the Northern Hemisphere, and such poplar is the main timber material in Xinjiang, China. However, poplar has defects that affect its ultimate bearing capacity. This study investigates the flexural behavior of the timber members from poplar. Three lengths of basalt fiber-reinforced polymer (BFRP) strips were used to strengthen timber beams from poplar with rectangular cross-sections. From the experimental data, the timber beams strengthened by 1900-mm-long and 50-mm-wide BFRP strips showed the best ultimate bearing capacity and maximum deflection of mid-span compared with the other two strengthened beams. The increments were 77.8% and 110.1% compared with the control beam. The assumption “plane section remains plane” remains practicable in the poplar beams bonded by BFRP strips, and the neutral axis of the strengthened beams had a tendency to move toward the tensile zone. Furthermore, the processes of the flexural behavior of the specimens were simulated by finite element analysis modeling, but all the analyzed values of ultimate bearing capacity and deflection of the beams are higher than those of the experiment. These values can roughly be used as reference for experimental results. However, accurate modeling should be developed and modified in subsequent research on timber beams from Xinjiang poplar.

Abstract The novel coronavirus disease (COVID-19) outbreak started in December 2019 in Wuhan, China, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The CT image is used to assess the disease progress, whereas the continued two times of negative results from SARS-CoV-2 nucleic acid detection had been considered as a criterion for ending antiviral treatment. We compared the two COVID-19 cases with similar backgrounds and CT image repeated intervals under treatment. Our report highlighted the unsynchronized expression in the changes of CT image and nucleic acid detection in COVID-19, and lasting positive nucleic acid test result in patients recovered from pneumonia. It may be contributed to recognize the disease and improve prevention.

Abstract. Machine learning shows enormous potential in facilitating decision-making regarding kidney diseases. With the development of data preservation and processing, as well as the advancement of machine learning algorithms, machine learning is expected to make remarkable breakthroughs in nephrology. Machine learning models have yielded many preliminaries to moderate and several excellent achievements in the fields, including analysis of renal pathological images, diagnosis and prognosis of chronic kidney diseases and acute kidney injury, as well as management of dialysis treatments. However, it is just scratching the surface of the field; at the same time, machine learning and its applications in renal diseases are facing a number of challenges. In this review, we discuss the application status, challenges and future prospects of machine learning in nephrology to help people further understand and improve the capacity for prediction, detection, and care quality in kidney diseases.

Summary: Multi-targeted kinase inhibitors, such as sorafenib, have been used in various malignancies, but their efficacy in clinical applications varies among individuals and lacks pretherapeutic prediction measures. We applied the concept of “click chemistry” to pathological staining and established a drug-loaded probe staining assay. We stained the cells and different types of pathological sections and demonstrated that the assay was reliable. We further verified in cells, cell-derived xenograft model, and clinical level that the staining intensity of the probe could reflect drug sensitivity. The stained samples from 300 patients who suffered from hepatocellular carcinoma and used the sorafenib probe also indicated that staining intensity was closely related to clinical information and could be used as an independent marker without undergoing sorafenib therapy for prognosis. This assay provided new ideas for multi-target drug clinical trials, pre-medication prediction, and pathological research. : Drugs; Medical Biochemistry; Biochemical Assay Subject Areas: Drugs, Medical Biochemistry, Biochemical Assay

Testis-expressed gene 11 (TEX11) mutation has been associated with non-obstructive azoospermia (NOA) and meiotic arrest. An analogous mutation of TEX11 in the mouse impairs meiosis and can be rescued by in vitro expansion of SSCs and gene therapy. However, a lack of genetic screening of a large cohort of Asian patients (including pedigree analysis) and proper functional evaluation limit the clinical application of TEX11 mutation screening. Thus, we performed whole-exome sequencing (WES) in 479 patients with NOA and identified three novel mutations (two splicing mutations and one missense mutation) in TEX11 in three pairs of siblings from three families and four novel pathogenic mutations (three frameshift mutations and a non-sense mutation) of TEX11 in four sporadic NOA-affected cases. Novel variants among family members were segregated by disease phenotype, and all the seven mutations were predicted to be pathogenic. Histological analysis showed that three patients with TEX11 mutations underwent meiotic arrest. The four mutations that resulted in protein truncations and defective meiosis-specific sporulation domain SPO22 were validated by Western blot. In total, we find seven of 479 patients of NOA (1.5%) carrying TEX11 mutations. Our study expands the knowledge of mutations of TEX11 gene in Asian patients with NOA. The high prevalence and X-linked inherited mode indicated that TEX11 might be included in genetic screening panels for the clinical evaluation of patients with NOA.

Innovative application of surface-enhanced Raman scattering (SERS) for rapid and nondestructive analyses has been gaining increasing attention for food safety and quality. SERS is based on inelastic scattering enhancement from molecules located near nanostructured metallic surfaces and has many advantages, including ultrasensitive detection and simple protocols. Current SERS-based quality analysis contains composition and structural information that can be used to establish an electronic file of the food samples for subsequent reference and traceability. SERS is a promising technique for the detection of chemical, biological, and harmful metal contaminants, as well as for food poisoning, and allergen identification using label-free or label-based methods, based on metals and semiconductors as substrates. Recognition elements, including immunosensors, aptasensors, or molecularly imprinted polymers, can be linked to SERS tags to specifically identify targeted contaminants and perform authenticity analysis. Herein, we highlight recent studies on SERS-based quality and safety analysis for different foods categories spanning the whole food chain, ‘from farm to table’ and processing, genetically modified food, and novel foods. Moreover, SERS detection is a potential tool that ensures food safety in an easy, rapid, reliable, and nondestructive manner during the COVID-19 pandemic.

The outbreak of the 2019 novel coronavirus disease (COVID-19) has impacted the mental health of healthcare providers at the frontline. Therefore, we conducted this study to estimate the prevalence rate of anxiety and insomnia and identify associated risk factors among healthcare workers in Jilin, China, during the period from January 25 to February 25, 2020. Zung's Self-Reported Anxiety Scale (SAS) and the Insomnia Severity Index (ISI) scale were used to diagnose anxiety and insomnia, respectively. Associated risk factors were identified through a multivariate logistic regression model. A total of 300 healthcare workers were invited and 236 completed the study. Of them, 234 (99.15%) were medical workers, 197 (83.47%) were working at frontline departments, and 159 (67.37%) were fighting against COVID-19. Fifty-seven respondents (24.15%) had anxiety (SAS index score ≥45) and 94 (39.83%) had insomnia (ISI score ≥8). Based on the multivariate analysis, contact with people from Hubei province during work (no vs not clear) [OR=0.25, 95%CI: 0.10-0.61] and personal protective equipment (PPE) (not in place vs in place) [OR=6.22, 95%CI: 2.23-17.40] were significantly correlated with anxiety. PPE (not in place vs in place) was the only significant risk factor of insomnia [OR=10.56, 95%CI: 4.00-27.87]. The prevalence of anxiety and insomnia was high in our study, reflecting the psychological impact of COVID-19 on healthcare workers. The unavailability of PPE in place was a significant risk factor of both anxiety and insomnia.

Summary: Chromatin remodelers often show broad expression patterns in multiple cell types yet can elicit cell-specific effects in development and diseases. Arid1a binds DNA and regulates gene expression during tissue development and homeostasis. However, it is unclear how Arid1a achieves its functional specificity in regulating progenitor cells. Using the tooth root as a model, we show that loss of Arid1a impairs the differentiation-associated cell cycle arrest of tooth root progenitors through Hedgehog (Hh) signaling regulation, leading to shortened roots. Our data suggest that Plagl1, as a co-factor, endows Arid1a with its cell-type/spatial functional specificity. Furthermore, we show that loss of Arid1a leads to increased expression of Arid1b, which is also indispensable for odontoblast differentiation but is not involved in regulation of Hh signaling. This study expands our knowledge of the intricate interactions among chromatin remodelers, transcription factors, and signaling molecules during progenitor cell fate determination and lineage commitment.

Premotor circuits in the brainstem project to pools of orofacial motoneurons to execute essential motor action such as licking, chewing, breathing, and in rodent, whisking. Previous transsynaptic tracing studies only mapped orofacial premotor circuits in neonatal mice, but the adult circuits remain unknown as a consequence of technical difficulties. Here, we developed a three-step monosynaptic transsynaptic tracing strategy to identify premotor neurons controlling vibrissa, tongue protrusion, and jaw-closing muscles in the adult mouse. We registered these different groups of premotor neurons onto the Allen mouse brain common coordinate framework (CCF) and consequently generated a combined 3D orofacial premotor atlas, revealing unique spatial organizations of distinct premotor circuits. We further uncovered premotor neurons that simultaneously innervate multiple motor nuclei and, consequently, are likely to coordinate different muscles involved in the same orofacial motor actions. Our method for tracing adult premotor circuits and registering to Allen CCF is generally applicable and should facilitate the investigations of motor controls of diverse behaviors.

Abstract Background Vascular maturity and functionality are closely associated with tumor progression and chemosensitivity. The antidiabetic agent metformin has shown its ability to inhibit tumor angiogenesis in metastatic breast cancer models. However, it remains unclear if or how metformin remodels the abnormal vasculature of metastatic breast cancer, while inhibiting angiogenesis. Methods Metastatic breast cancer models were constructed to compare microvessel density (MVD), vascular maturity and function, lung metastasis and chemosensitivity in metformin-treated or untreated mice. Protein array assay and transcriptome sequencing were performed for genetic screening. Lentiviral shRNA-PDGF-B transfection was used for observing the contribution of PDGF-B knockdown to metformin’s vascular effects. Results Metastatic breast cancers were characterized by an excessively angiogenic, immature and morphologically abnormal vasculature. Compared to control, metformin significantly reduced MVD, leakage and hypoxia, and increased vascular mural cells coverage and perfusion, namely, “vessel normalization”. Metformin at human blood concentrations had no direct effect on the migration and proliferation of cancer cells. Based on that, reduced lung metastasis of the primary tumor and improved chemosensitization by metformin were assumed to be mediated via metformin’s vascular effects. Further results of genetic screening and in vivo experiments showed that the downregulation of platelet-derived growth factor B (PDGF-B) greatly contributed to the metformin-induced vessel normalization. Conclusions These findings provide pre-clinical evidences for the vascular mechanism of metformin-induced metastasis inhibition and the chemosensitization of metastatic breast cancers.

Abstract. Background:. Accurate estimation of the glomerular filtration rate (GFR) and staging of chronic kidney disease (CKD) are important. Currently, there is no research on the differences in several estimated GFR equations for staging CKD in a large sample of centenarians. Thus, this study aimed to investigate the differences in CKD staging with the most commonly used equations and to analyze sources of discrepancy. Methods:. A total of 966 centenarians were enrolled in this study from June 2014 to December 2016 in Hainan province, China. The GFR with the Modification of Diet in Renal Disease (MDRD), Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Berlin Initiative Study 1 (BIS1) equations were estimated. Agreement between these equations was investigated with the κ statistic and Bland-Altman plots. Sources of discrepancy were investigated by partial correlation analysis. Results:. The κ values of the MDRD and CKD-EPI equations, MDRD and BIS1 equations, and CKD-EPI and BIS1 equations were 0.610, 0.253, and 0.381, respectively. Serum creatinine (Scr) explained 10.96%, 41.60% and 17.06% of the variability in these three comparisons, respectively. Serum uric acid (SUA) explained 3.65% and 5.43% of the variability in the first 2 comparisons, respectively. Gender was associated with significant differences in these 3 comparisons (P