Neuron-derived neurotrophic factor promotes the differentiation of intramuscular and subcutaneous adipocytes in goat.

Adipocyte play an important role in human health and meat quality by influencing the tenderness, flavor, and juiciness of mutton It has been shown that neuron-derived neurotrophic factor (NENF) is closely related to energy metabolism and adipocyte differentiation in bovine. However, the role of NENF in the goats remains unclear. The aim of this study was to detect the expression of NENF in goat subcutaneous and intramuscular adipocytes, temporal expression profiles of the NENF, and overexpressed NENF on the differentiation of different adipocytes. In this study, PCR amplification successfully cloned the goat NENF gene with a fragment length of 521 bp. In addition, the time point of highest expression of NENF differed between these two adipocytes differentiation processes. Overexpression of NENF in intramuscular and subcutaneous adipocytes promoted the expression levels of differentiation markers CEBPß and SREBP, which in turn promoted the differentiation of intramuscular and subcutaneous adipocytes. This study will provide basic data for further study of the role of goats in goat adipocyte differentiation and for the final elucidation of its molecular mechanisms in regulating goat adipocyte deposition.

J-shaped association of operation duration and blood transfusion risk in patients undergoing primary total knee arthroplasty.

PURPOSE: Blood transfusion is a common perioperative complication of primary total knee arthroplasty (TKA) that can lead to adverse outcomes, prolonged hospital stays, and increased medical costs. The purpose of our study was to explore the risk factors for blood transfusion and to establish whether operation duration is independently related to blood transfusion risk in patients undergoing primary TKA after adjusting for other covariates. METHODS: This was a secondary analysis of data from a retrospective cohort study involving patients who underwent primary TKA in Singapore. The patients' baseline data, comorbidity, and surgical characteristics were collected. The independent variable was operation duration and the dependent variable was blood transfusion events. Patients were divided into three groups according to operation durations (90 and 120 min). Univariate logistic regression was used to explore the risk factors associated with blood transfusion after primary TKA. Multivariate analysis was used to assess the independent effect of operation duration on blood transfusion risk after adjusting for other covariates. Additionally, we performed subgroup analyses to identify specific groups, test the robustness of the relationships, and explore whether there were interactions between the different variables. Furthermore, restricted cubic splines (RCS) were used to identify the relationship between the two variables. RESULTS: A total of 2,562 patients were included in the study, of whom 136 (5.61%) had a transfusion event. Operation durations were 95.55 ± 36.93 and 83.86 ± 26.29 min for blood transfused and non-transfused patients, respectively. Univariate logistic regression analysis showed that age, BMI, ASA status, Hb level, OSA, CHF, creatinine level > 2 mg/dL, and anaesthesia type were risk factors for blood transfusion. After adjusting for all covariates, multivariate logistic regression models showed that operation duration was positively associated with blood transfusion risk (odds ratio [OR] = 1.87, 95% CI = 1.174-2.933, P = 0.007). Compared to patients with an operation duration of less than 90 min, those with an operation duration of more than 120 min had a 2.141-fold increased risk of blood transfusion (OR = 2.141, 95% CI = 1.035-4.265, P = 0.035). Stratified analysis results showed that the association persisted in patients aged > 50 years, Chinese, BMI > 30 kg/m 2, Hb level > 11 g/dL, ASA status levels 2 and 3, general anaesthesia, and unilateral primary TKA. A non-linear (P-non-linear = 0.30) and J-shaped relationship was identified. The risk of transfusion increased as the operation duration decreased or exceeded the inflection point (73.2 min). CONCLUSION: Our study demonstrated a non-linear and J-shaped relationship between operation duration and blood transfusion events in patients undergoing primary TKA. Blood transfusion risk was the lowest when the operation duration was 73.2 min. A shorter operation duration implies irregular surgical procedures and incomplete intraoperative haemostasis, leading to increased perioperative blood loss and blood transfusion. These results will be useful for clinical decision-making.

Lab-on-Device Synthesis of Hierarchical Macro/Mesoporous WO3 Semiconducting Films for High-Performance H2S Sensing.

The performance consistency of the gas sensor is strongly dependent on the interface binding between the sensitive materials and the electrodes. Traditional powder coating methods can inevitably lead to differences in terms of substrate-film interface interaction and device performance, affecting the stability and lifetime. Thus, efficient growth of sensitive materials on device substrates is crucial and essential to enhance the sensing performance, especially for stability. Herein, hierarchically ordered macro/mesoporous WO3 films are in situ synthesized on the electrode via a facile soft/hard dual-template strategy. Orderly arrayed uniform polystyrene (PS) microspheres with tailored size (ca. 1.2 µm) are used as a hard template, and surfactant Pluronic F127 as a soft template can co-assemble with tungsten precursor into ordered mesostructure in the interstitials of PS colloidal crystal induced by solvent evaporation. Benefiting from its rich porosity and high stability, the macro/mesoporous WO3-based sensor shows high sensitivity (Rair/Rgas = 307), fast response/recovery speed (5/9 s), and excellent selectivity (SH2S/Smax > 7) toward 50 ppm H2S gas (a biomarker for halitosis). Significantly, the sensors exhibit an extended service life with a negligible change in sensing performance within 60 days. This lab-on-device synthesis provides a platform method for constructing stable nanodevices with good consistency and high stability, which are highly desired for developing high-performance sensors.

Current Knowledge on the Preparation and Benefits of Cruciferous Vegetables as Relates to In Vitro, In Vivo, and Clinical Models of Inflammatory Bowel Disease.

Inflammatory bowel disease is a chronic condition with a significant economic and social burden. The disease is complex and challenging to treat because it involves several pathologies, such as inflammation, oxidative stress, dysbiosis, and intestinal damage. The search for an effective treatment has identified cruciferous vegetables and their phytochemicals as potential management options for inflammatory bowel disease because they contain prebiotics, probiotics, and anti-inflammatory and antioxidant metabolites essential for a healthy gut. This critical narrative style review provides a robust insight into the pharmacological effects and benefits of crucifers and their documented bioactive compounds in in vitro and in vivo models, as well as clinical inflammatory bowel disease. The review highlights the significant impact of crucifer preparation and the presence of glucosinolates, isothiocyanates, flavonoids, and polyphenolic compounds, which are essential for the anti-inflammatory and antioxidative benefits of cruciferous vegetables, as well as their ability to promote the healthy microbial community and maintain the intestinal barrier. This review may serve as a viable nutritional guide for future research on methods and features essential to developing experiments, preventions, and treatments for inflammatory bowel disease. There is limited clinical information and future research may utilize current innovative tools, such as metabolomics, for adequate knowledge and effective translation into clinical therapy.

Chiral-structured heterointerfaces enable durable perovskite solar cells.

Mechanical failure and chemical degradation of device heterointerfaces can strongly influence the long-term stability of perovskite solar cells (PSCs) under thermal cycling and damp heat conditions. We report chirality-mediated interfaces based on R-/S-methylbenzyl-ammonium between the perovskite absorber and electron-transport layer to create an elastic yet strong heterointerface with increased mechanical reliability. This interface harnesses enantiomer-controlled entropy to enhance tolerance to thermal cycling-induced fatigue and material degradation, and a heterochiral arrangement of organic cations leads to closer packing of benzene rings, which enhances chemical stability and charge transfer. The encapsulated PSCs showed retentions of 92% of power-conversion efficiency under a thermal cycling test (-40°C to 85°C; 200 cycles over 1200 hours) and 92% under a damp heat test (85% relative humidity; 85°C; 600 hours).

The Inverted U-Shaped Association between Serum Vitamin D and Serum Uric Acid Status in Children and Adolescents: A Large Cross-Sectional and Longitudinal Analysis.

BACKGROUND: Serum vitamin D is associated with hyperuricemia. However, previous studies have been controversial, with limited focus on children and adolescents. OBJECTIVE: This study aimed to examine the cross-sectional and longitudinal associations between serum vitamin D and serum uric acid (SUA) levels in children and adolescents. METHODS: The cross-sectional survey comprised 4777 participants aged 6 to 18 years, while the longitudinal survey involved 1641 participants aged 6 to 12 years, all derived from an ongoing cohort study in Shenzhen, China. Restricted cubic splines were used to visualize the dose-response relationship between vitamin D and SUA and the risk of higher SUA status. Two-segment generalized linear models (GLM) and logistic models were used to assess the association between vitamin D and SUA and higher SUA status, respectively. The longitudinal analysis used GLM. RESULTS: We observed an inverted U-shaped relationship between vitamin D and SUA (p-overall < 0.0001, p-nonlinear = 0.0002), as well as the risk of higher SUA status (p-overall = 0.0054, p-nonlinear = 0.0015), with the vitamin D inflection point at 24.31 and 21.29 ng/mL, respectively. A 10 ng/mL increment in 25(OH)D3 levels, when below 20.92 ng/mL, was associated with a 68% rise in the risk of higher SUA status (OR: 1.68, 95%CI: 1.07-2.66). Conversely, when 25(OH)D3 levels were above or equal to 20.92 ng/mL, a 10 ng/mL increment was associated with a 45% reduction risk of higher SUA status (OR: 0.55, 95%CI: 0.36-0.84). Longitudinal analysis indicated that the annual change of SUA was from -4.80 (ß, 95%CI: -10.74, 1.13) to -9.00 (ß, 95%CI: -15.03, -2.99) and then to -6.77 (ß, 95%CI: -12.83, -0.71, p for trend = 0.0212) µmol/L when increasing the quartile of vitamin D3. CONCLUSIONS: An inverse U-shaped relationship was observed between vitamin D and SUA as well as the risk of higher SUA status. Sufficient vitamin D levels appear to play a preventative role against the age-related increase in SUA. Ensuring adequate vitamin D levels may be beneficial in improving uric acid metabolism.

Interface engineering of hierarchical flower-like N, P, O-doped NixPy self-supported electrodes for highly efficient water-to-hydrogen fuel/oxygen conversion.

Rational construction of efficient bifunctional catalysts with robust catalytic activity and durability is significant for overall water splitting (conversion between water and hydrogen fuel/oxygen) using non-precious metal systems. In this work, the hierarchically porous N, P, O-doped transition metal phosphate in the Ni foam (NF) electrode (hollow flower-like NPO/NixPy@NF) was prepared through facile hydrothermal method coupled with phosphorization treatment. The hierarchical hollow flower-like NPO/NixPy@NF electrodes exhibited high bifunctional activity and stability for hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) in alkaline solutions. The optimized electrode showed low overpotentials of 76 and 240 mV for HER and OER to reach a current density of 10 mA cm-2, respectively. Notably, the NPO/NixPy@NF electrode only required a low voltage of 1.99 V to reach the current densities of 100 mA cm-2 with long-term stability for overall water splitting using the NPO/NixPy@NF|| NPO/NixPy@NF cell, surpassing that of the Pt/C-RuO2 (2.24 V@ 100 mA cm-2). The good catalytic and battery performance should be attributed to i) the open hierarchical structure that enhanced the mass transfer; ii) a highly conductive substrate that accelerated the electron transfer; iii) the rich heterojunction and strong synergy between Ni2P and Ni5P4 that improved the catalytic kinetic; iv) the proper-thickness amorphous phosphorus oxide nitride (PON) shell that realized the stability. This work demonstrates a promising methodology for designing bifunctional transition metal phosphides with high performance for efficient water splitting.

Synergy of Oxygen Vacancy and Surface Modulation Endows Hollow Hydrangea-like MnCo2O4.5 with Enhanced Capacitive Performance.

Surface chemistry and bulk structure jointly play crucial roles in achieving high-performance supercapacitors. Here, the synergistic effect of surface chemistry properties (vacancy and phosphorization) and structure-derived properties (hollow hydrangea-like structure) on energy storage is explored by the surface treatment and architecture design of the nanostructures. The theoretical calculations and experiments prove that surface chemistry modulation is capable of improving electronic conductivity and electrolyte wettability. The structural engineering of both hollow and nanosheets produces a high specific surface area and an abundant pore structure, which is favorable in exposing more active sites and shortens the ion diffusion distance. Benefiting from its admirable physicochemical properties, the surface phosphorylated MnCo2O4.5 hollow hydrangea-like structure (P-MnCoO) delivers a high capacitance of 425 F g-1 at 1 A g-1, a superior capability rate of 63.9%, capacitance retention at 10 A g-1, and extremely long cyclic stability (91.1% after 10,000 cycles). The fabricated P-MnCoO/AC asymmetric supercapacitor achieved superior energy and power density. This work opens a new avenue to further improve the electrochemical performance of metal oxides for supercapacitors.

Merging Flow Synthesis and Enzymatic Maturation to Expand the Chemical Space of Lasso Peptides.

Many peptidic natural products, such as lasso peptides, cyclic peptides, and cyclotides, are conformationally constrained and show biological stability, making them attractive scaffolds for drug development. Although many peptides can be synthesized and modified through chemical methods, knot-like lasso peptides such as microcin J25 (MccJ25) and their analogues remain elusive. As the chemical space of MccJ25 analogues accessible through purely biological methods is also limited, we proposed a hybrid approach: flow-based chemical synthesis of non-natural precursor peptides, followed by in vitro transformation with recombinant maturation enzymes, to yield a more diverse array of lasso peptides. Herein, we established the rapid, flow-based synthesis of chemically modified MccJ25 precursor peptides (57 amino acids). Heterologous expression of enzymes McjB and McjC was extensively optimized to improve yields and facilitate the synthesis of multiple analogues of MccJ25, including the incorporation of non-canonical tyrosine and histidine derivatives into the lasso scaffold. Finally, using our chemoenzymatic strategy, we produced a biologically active analogue containing three d-amino acids in the loop region and incorporated backbone N-methylations. Our method provides rapid access to chemically modified lasso peptides that could be used to investigate structure-activity relationships, epitope grafting, and the improvement of therapeutic properties.

Genome assembly of M. spongiola and comparative genomics of the genus Morchella provide initial insights into taxonomy and adaptive evolution.

Morchella spongiola is a highly prized mushroom for its delicious flavor and medical value and is one of the most flourishing, representative, and dominant macrofungi in the Qilian Mountains of the Qinghai-Tibet Plateau subkingdoms (QTPs). However, the understanding of M. spongiola remains largely unknown, and its taxonomy is ambiguous. In this study, we redescribed a unique species of M. spongiola, i.e., micromorphology, molecular data, genomics, and comparative genomics, and the historical biogeography of M. spongiola were estimated for 182 single-copy homologous genes. A high-quality chromosome-level reference genome of M. spongiola M12-10 was obtained by combining PacBio HiFi data and Illumina sequencing technologies; it was approximately 57.1 Mb (contig N50 of 18.14 Mb) and contained 9775 protein-coding genes. Comparative genome analysis revealed considerable conservation and unique characteristics between M. spongiola M12-10 and 32 other Morchella species. Molecular phylogenetic analysis indicated that M. spongiola M12-10 is similar to the M. prava/Mes-7 present in sandy soil near rivers, differentiating from black morels ~ 43.06 Mya (million years ago), and diverged from M. parva/Mes-7 at approximately 12.85 Mya (in the Miocene epoch), which is closely related to the geological activities in the QTPs (in the Neogene). Therefore, M. spongiola is a unique species rather than a synonym of M. vulgaris/Mes-5, which has a distinctive grey-brown sponge-like ascomata. This genome of M. spongiola M12-10 is the first published genome sequence of the species in the genus Morchella from the QTPs, which could aid future studies on functional gene identification, germplasm resource management, and molecular breeding efforts, as well as evolutionary studies on the Morchella taxon in the QTPs.

MRI-based deep learning and radiomics for prediction of occult cervical lymph node metastasis and prognosis in early-stage oral and oropharyngeal squamous cell carcinoma: a diagnostic study.

INTRODUCTION: The incidence of occult cervical lymph node metastases (OCLNM) is reported to be 20%-30% in early-stage oral cancer and oropharyngeal cancer. There is a lack of an accurate diagnostic method to predict occult lymph node metastasis and to help surgeons make precise treatment decisions. AIM: To construct and evaluate a preoperative diagnostic method to predict occult lymph node metastasis (OCLNM) in early-stage oral and oropharyngeal squamous cell carcinoma (OC and OP SCC) based on deep learning features (DLFs) and radiomics features. METHODS: A total of 319 patients diagnosed with early-stage OC or OP SCC were retrospectively enrolled and divided into training, test and external validation sets. Traditional radiomics features and DLFs were extracted from their MRI images. The least absolute shrinkage and selection operator (LASSO) analysis was employed to identify the most valuable features. Prediction models for OCLNM were developed using radiomics features and DLFs. The effectiveness of the models and their clinical applicability were evaluated using the area under the curve (AUC), decision curve analysis (DCA) and survival analysis. RESULTS: Seventeen prediction models were constructed. The Resnet50 deep learning (DL) model based on the combination of radiomics and DL features achieves the optimal performance, with AUC values of 0.928 (95% CI: 0.881-0.975), 0.878 (95% CI: 0.766-0.990), 0.796 (95% CI: 0.666-0.927) and 0.834 (95% CI: 0.721-0.947) in the training, test, external validation set1 and external validation set2, respectively. Moreover, the Resnet50 model has great prediction value of prognosis in patients with early-stage OC and OP SCC. CONCLUSION: The proposed MRI-based Resnet50 deep learning model demonstrated high capability in diagnosis of OCLNM and prognosis prediction in the early-stage OC and OP SCC. The Resnet50 model could help refine the clinical diagnosis and treatment of the early-stage OC and OP SCC.

Does Social Support Moderate the Relationship between Frailty and Functional Ability Trajectory Among Community-Dwelling Older Adults?

BACKGROUND: Functional ability is the important prerequisite to live independently and achieve aging in place, which depends on the complex interaction of intrinsic and extrinsic factors. Identifying the trends and influencing factors of functional ability would contribute to the accurate assessment and intervention of geriatric health. This study aimed to disentangle the moderating effect of three types of social support, namely objective support, subjective support and support utilization, on the relationship between frailty and functional ability trajectories. METHODS: This was a secondary analysis using data from a prospective three-wave study with a sample of 777 Chinese community-dwelling older adults. Social support was assessed using the Social Support Rating Scale. Frailty was assessed using the FRAIL Scale. Functional ability was measured by the Lawton Instrumental Activities of Daily Living Scale. Latent growth curve models were implemented to test their relationships. RESULTS: Objective support but not subjective support or support utilization moderated on the relationship between frailty and functional ability slope. Functional ability decline over time was buffered by objective support among robust individuals but exacerbated among (pre)frail individuals. CONCLUSIONS: The moderating effect of social support on the relationship between frailty and functional ability trajectory varies by support types, which reminded that social support may be a promising intervention target to maintain functional independence for frail individuals, opening up a new perspective on social support in the field of disability prevention. Effective interventions should particularly address objective support in conjunction with empowering frail older population to optimize the trajectory of functional ability.

Screening, identification and evaluation of an acidophilic strain of Bacillus velezensis B4-7 for the biocontrol of tobacco bacterial wilt.

Tobacco (Nicotiana tabacum L.) bacterial wilt, caused by Ralstonia solanacearum, is indeed a highly destructive plant disease, leading to substantial damage in tobacco production. While biological control is considered an effective measure for managing bacterial wilt, related research in this area has been relatively limited compared to other control methods. In order to discover new potential antagonistic bacteria with high biocontrol efficacy against tobacco bacterial wilt, we conducted an analysis of the microbial composition differences between disease-suppressive and disease-conducive soils using Illumina sequencing. As a result, we successfully isolated six strains from the disease-suppressive soil that exhibited antibacterial activity against Ralstonia solanacearum. Among these strains, B4-7 showed the strongest antibacterial activity, even at acidic conditions with a pH of 4.0. Based on genome analysis using Average Nucleotide Identity (ANI), B4-7 was identified as Bacillus velezensis. In greenhouse and field trials, strain B4-7 significantly reduced the disease index of tobacco bacterial wilt, with control efficiencies reaching 74.03% and 46.88% respectively. Additionally, B4-7 exhibited plant-promoting abilities that led to a 35.27% increase in tobacco production in field conditions. Quantitative real-time (qPCR) analysis demonstrated that strain B4-7 effectively reduced the abundance of R. solanacearum in the rhizosphere. Genome sequencing and Liquid Chromatography-Mass Spectrometry (LC-MS) analysis revealed that strain B4-7 potentially produces various lipopeptide metabolites, such as microlactin, bacillaene, difficidin, bacilysin, and surfactin. Furthermore, B4-7 influenced the structure of the rhizosphere soil microbial community, increasing bacterial abundance and fungal diversity, while also promoting the growth of different beneficial microorganisms. In addition, B4-7 enhanced tobacco's resistance to R. solanacearum by increasing the activities of defense enzymes, including superoxide dismutase (SOD), phenylalanine ammonia-lyase (PAL), peroxidase (POD), catalase (CAT), and polyphenol oxidase (PPO). Collectively, these findings suggest that B. velezensis B4-7 holds significant biocontrol potential and can be considered a promising candidate strain for eco-friendly management of tobacco bacterial wilt.

Non-transcriptional regulatory activity of SMAX1 and SMXL2 mediates karrikin-regulated seedling response to red light in Arabidopsis.

Karrikins and strigolactones govern plant development and environmental responses through closely related signaling pathways. The transcriptional repressor proteins SUPPRESSOR OF MAX2 1 (SMAX1), SMAX1-like2 (SMXL2), and D53-like SMXLs, mediate karrikin and strigolactone signaling through direct binding downstream genes or by inhibiting the activities of transcription factors. In this study, we characterized the non-transcriptional regulatory activities of SMXL proteins in Arabidopsis. We discovered that SMAX1 and SMXL2 with mutations in their ethylene-response factor-associated amphiphilic repression (EAR) motif had undetected or weak transcriptional repression activities, but can still partially rescued the hypocotyl elongation defects and fully reversed the cotyledon epinasty defects of smax1 smxl2 mutant. SMAX1 and SMXL2 directly interacted with PHYTOCHROME INTERACTION FACTOR 4 (PIF4) and PIF5 and enhanced the protein stability of PIF4 and PIF5 by interacting with phytochrome B (phyB) and suppressing the association of phyB with PIF4 and PIF5. The karrikin-responsive genes were further identified by treatment with GR24ent-5DS, a GR24 analog showing karrikin activity. Interestingly, INDOLE-3-ACETIC ACID INDUCIBLE 29 (IAA29) expression was repressed by GR24ent-5DS treatment in a PIF4- and PIF5-dependent and EAR-independent manner, whereas KARRIKIN UPREGULATED F-BOX 1 (KUF1) expression was induced in a PIF4- and PIF5-independent and EAR-dependent manner. Furthermore, the non-transcriptional regulatory activity of SMAX1 that is independent of the EAR motif had a global effect on gene expression. Taken together, these results reveal that the non-transcriptional regulatory activities of SMAX1 and SMXL2 mediates the karrikin-regulated seedling response to red light.

Joint trajectories of loneliness, social isolation and sarcopenia and associations with adverse outcomes: A prospective cohort study.

This study aimed to examine joint trajectories of loneliness, social isolation and sarcopenia and their associations with adverse outcomes. A total of 4701 participants aged ≥60 years who had a baseline and at least one follow-up assessment of loneliness, social isolation and sarcopenia across 2011, 2013 and 2015 waves in China Health and Retirement Longitudinal Study. Adverse outcomes were obtained in 2018 wave. Joint trajectories were fit using the parallel process latent class growth analysis, and their associations with adverse outcomes were evaluated using modified Poisson regression. Joint trajectory patterns for social relationship and sarcopenia did not vary by the assessment for sarcopenia, but did vary by the assessment for social relationship. Older adults exhibit distinct joint trajectories and those with persistent combination of loneliness or social isolation and sarcopenia experience greatest risk of adverse outcomes. These findings implicate integration of health care and social care for community-dwelling older adults.

Abnormal Bone Turnover Observed in Obese Children Based on Puberty Stage -Specific Bone Turnover Marker Reference.

CONTEXT: Childhood and adolescence are critical periods for lifelong bone health. The impact of obesity on these phases is controversial, which may be due to the lack of standards for age-, sex-, and puberty-specific Bone turnover markers (BTMs) which could sensitively reflect bone metabolism. OBJECTIVE: To generate age-, sex, and puberty stage-specific BTMs reference curves in children and adolescents and to explore the effect of obesity on bone metabolism in the Chinese population. METHODS: Our study was part of the Evaluation and Monitoring on School-based Nutrition and Growth in Shenzhen study. 800 participants aged 6∼18 years with normal body mass index (BMI) were selected to establish BTM reference curves for boys and girls at different ages under different pubertal development stages. Additionally, 200 participants with obesity (BMI >P95th) were matched with healthy children from the original cohort at a 1:1 ratio. All participants underwent bone mineral density assessment, and serum levels of P1NP and ß-CTX were measured. RESULTS: The BTMs values presented significant age, sex, and puberty stage differences. Analysis of serum BTMs based on the established reference revealed a higher percentage of low-level P1NP in boys with obesity (P=0.005); no significant difference was observed in girls. However, the obese group showed a significantly higher proportion of high ß-CTX levels for girls, not boys (P=0.022). CONCLUSIONS: We provide age-, sex-, and puberty stage-specific P1NP and ß-CTX reference curve. According to these, obesity appeared to be a negative factor for bone formation in boys and for bone resorption in girls.

Spatially ordered NiOOH-ZnS/CdS heterostructures with an efficient photo-carrier transmission channel for markedly improved H2 production.

Spatially-ordered 1D nanocrystal-based semiconductor nanostructures possess distinct merits for photocatalytic reaction, including large surface area, fast carrier separation, and enhanced light scattering and absorption. Nevertheless, establishing a valid photo-carrier transmission channel is still crucial yet challenging for semiconductor heterostructures to realize efficient photocatalysis. In this work, spatially ordered NiOOH-ZnS/CdS heterostructures were constructed by sequential ZnS coating and NiOOH photo-deposition on multi-armed CdS, which consists of {112̄0}-faceted wurtzite nanorods grown epitaxially on {111}-faceted zinc blende core. Intriguingly, the surface photovoltage spectroscopy and PbO2 photo-deposition results suggest that the photogenerated holes of CdS were first transferred to the Zn-vacancy level of ZnS and then to NiOOH, as driven by the built-in electric field between ZnS and CdS and the hole-extracting effect of the NiOOH cocatalyst, leading to the efficient charge separation of NiOOH-ZnS/CdS. With visible-light (λ > 420 nm) irradiation, NiOOH-ZnS/CdS exhibited a distinguished H2-evolution rate of 152.20 mmol g-1 h-1 (apparent quantum efficiency of 40.9% at 420 nm), approximately 18 folds that of 3 wt% Pt-loaded CdS and much higher than that of ZnS/CdS and NiOOH-CdS counterparts as well as the most reported CdS-containing photocatalysts. Moreover, the cycling and long-term H2 generation tests manifested the outstanding photocatalyst stability of NiOOH-ZnS/CdS. The study results presented here may propel the controllable design of highly-active nanomaterials for solar conversion and utilization.

Suberanilohydroxamic acid (SAHA), a HDAC inhibitor, suppresses the effect of Treg cells by targeting the c-Myc/CCL1 pathway in glioma stem cells and improves PD-L1 blockade therapy.

PURPOSE: A strong immunosuppressive tumor microenvironment (TME) represents the major barrier responsible for the failure of current immunotherapy approaches in treating Glioblastoma Multiforme (GBM). Within the TME, the regulatory T cells (Tregs) exert immunosuppressive effects on CD8+ T cell - mediated anti-cancer immune killing. Consequently, targeting and inhibiting their immunosuppressive function emerges as an effective therapeutic strategy for GBM. The present study aimed to investigate the mechanisms and effects of Suberanilohydroxamic Acid (SAHA), a histone deacetylase inhibitor, on immunosuppressive Tregs. METHODS: The tumor-infiltrating immune cells in the immunocompetent GBM intracranial implanted xenograft mouse model were analyzed by immunohistochemistry and flow cytometry techniques. The mRNA expressions were assessed through the RT-qPCR method, while the related protein expressions were determined using western blot, ELISA, immunofluorescence (IF), and flow cytometry techniques. The relationship between c-Myc and C-C motif Chemokine Ligand 1 (CCL1) promotor was validated through a dual-luciferase reporter assay system and chromatin immunoprecipitation. RESULTS: SAHA suppressed effectively tumor growth and extended significantly overall survival in the immunocompetent GBM intracranial xenograft mouse model. Additionally, it promoted the infiltration of CD8+ T lymphocytes while suppressed the infiltration of CD4+ CD25+ Tregs. Furthermore, SAHA enhanced anti-PD-L1 immune therapy in the intracranial xenograft of mice. Mechanistically, SAHA exerted its effects by inhibiting histone deacetylase 2 (HDAC2), thereby suppressing the binding between c-Myc and the CCL1 promotor. CONCLUSION: SAHA inhibited the binding of c-Myc with the CCL1 promoter and then suppressed the transcription of CCL1.Additionally, it effectively blocked the interplay of CCL1-CCR8, resulting in reduced activity of Tregs and alleviation of tumor immunosuppression.

Metagenomic next-generation sequencing for the diagnosis of neurobrucellosis.

Objective: This study investigates the application of metagenomic next-generation sequencing (mNGS) in the diagnosis of neurobrucellosis (NB). Methods: We retrospectively analyzed patients diagnosed with NB who underwent cerebrospinal fluid (CSF) mNGS testing in Xijing Hospital from 2015 to 2021. Results: Among the 20 individuals included in the study, the serum rose bengal test was positive in 11 out of 16 cases, serum agglutination test was positive in 13 out of 16 cases, CSF culture was positive in 6 out of 11 cases, and CSF mNGS tests were positive in 18 out of 20 cases. Conclusion: CSF mNGS demonstrates superior sensitivity; therefore, it is recommended to collect CSF for mNGS testing prior to antibiotic therapy when NB is suspected.

Neurobrucellosis (NB) is a disease of the nervous system caused by a type of bacteria called Brucella. It is rare, serious and manifests inconsistently, making it hard to diagnose. Metagenomic next-generation sequencing (mNGS) is a new way to detect disease-causing bacteria by looking at their genetic material. mNGS is fast, accurate and covers a wide range of disease-causing bacteria. We looked back at patients diagnosed with NB at Xijing Hospital between 2015 and 2021 and tested samples of the fluid surrounding the brain and the spinal cord, called cerebrospinal fluid (CSF), by mNGS. A total of 20 patients were included in the study. Compared with the traditional methods, mNGS of CSF samples showed advantages in diagnosing NB. However, antibiotics may affect the results.