Prevalence and risk factors of subjective cognitive decline in older adults in Baotou, China: a cross-sectional study.

Objectives: Subjective cognitive decline (SCD) as a stage between healthy cognition and early neurocognitive disorders, has been proposed to be helpful in the diagnosis of prodromal neurocognitive disorders. To investigate the prevalence of SCD and the related risk factors on the prevalence. Methods: A cross-sectional study involving 1,120 elderly subjects residing in Baotou, China. From June 2021 to June 2023, the data were gathered by research assistants with training utilizing standardized questionnaires. The following factors were evaluated: subjective cognitive decline, physical and cognitive activity levels, past medical history, demographics, instrumental activities of daily living, and cognitive function. Risk factors of SCD were used chi-square tests and multivariate logistic regression analysis. Results: The prevalence of SCD was 43.8%. Permanent residence, marital status, BMI, dietary habits, average sleep duration per night, smoking, diabetes, coronary heart disease, and visual impairment were significantly associated with SCD (p < 0 0.05). Multivariable logistic regression analysis showed obesity, vegetarian-based, smoking for a long time, diabetes and coronary heart disease, visual impairment, no spouse, and average sleep duration per night <6 h were independent risk factors for SCD. Based on the gender analysis, the difference in marital status, dietary habits, average sleep duration per night, smoking, drinking, and hypertension was statistically significant (p < 0.001). Conclusion: The prevalence of subjective cognitive decline was high among elder adults. We discovered significant differences in the prevalence or risk factors for SCD between men and women based on their sex. This study provides a more theoretical basis for the early prevention and screening of cognitive impairment diseases in the elderly population.

Dynamics of fermentation quality, bacterial communities, and fermentation weight loss during fermentation of sweet sorghum silage.

BACKGROUND: Sweet sorghum is used mainly as an energy crop and feed crop in arid and semiarid regions, and ensiling is a satisfactory method for preserving high-quality sweet sorghum. The aim of this study was to reveal the dynamics of the fermentation quality, bacterial communities, and fermentation weight loss (FWL) of sweet sorghum silage during fermentation. METHODS: Sweet sorghum was harvested at the first inflorescence spikelet stage and ensiled without (CK) or with lactic acid bacterial (LAB) additives (L). After ensiling, samples were collected on days 0, 1, 3, 5, 15, 40, and 100 to assess the fermentation quality, bacterial communities, and FWL. RESULTS: For CK and L, on day 1, the pH was 5.77 and 5.57, respectively, and the lactic acid (LA) was 1.30 and 2.81 g/kg dry matter (DM), respectively. Compared with CK, L had a lower pH and higher LA from days 1 to 5 (P < 0.05), a lower FWL from days 5 to 100 (P < 0.05), and a greater abundance of Lactiplantibacillus from days 1 to 15 (P < 0.05). The main bacterial genera were Leuconostoc and Weissella in CK and Lactiplantibacillus, Leuconostoc, and Weissella in L on day 1; Lactiplantibacillus in all silages from days 3 to 40; and Lactiplantibacillus and Lentilactobacillus in all silages on day 100. CONCLUSIONS: Sweet sorghum silage fermented relatively slowly during the first day. Moreover, inoculation with LAB accelerated fermentation and optimized bacterial communities during the initial fermentation phase. Inoculation with LAB also reduced the silage FWL, and the LAB succession relay occurred in the silage throughout the fermentation process.

Long-Term Remission With Allo-HSCT for t(1;8)(q25;p11) Translocation: A Rare Case Report and Literature Review.

BACKGROUND: The 8p11 myeloproliferative syndrome (EMS), a rare disorder characterized by translocations and interchanges at chromosome 8p11, is usually refractory to chemotherapy, and allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently the only promising treatment for long-term remission. Among 14 translocation partners associated with EMS, t(1;8)(q25;p11) are very uncommon, with only four cases previously reported in peer-reviewed journals in English. CASE PRESENTATION: Here we report a 43-year-old man who presented with atypical peripheral T-cell lymphomas. Translocations between chromosomes 1q25 and 8p11 were detected during a bone marrow karyotype examination of 20 metaphases, and fluorescence in situ hybridization (FISH) revealed a positive rearrangement for the FGFR1 locus, confirming the diagnosis of EMS with t(1;8)(q25;p11). Despite rapid disease progression, he maintained remission for 27 months after admission due to aggressive chemotherapy combined with early allogeneic peripheral blood stem cell transplantation. We also conducted a literature review for 12 EMS patients treated with allo-HSCT who had rare karyotypes to better understand their clinicopathologic features and disease management. CONCLUSION: we report the first case of EMS with t(1;8)(q25;p11) to have a favorable outcome after allo-HSCT. The encouraging results support the use of aggressive chemotherapy in conjunction with early allo-HSCT for EMS patients with t(1;8)(q25;p11).

Combination Antitumor Activation of Anlotinib with Radiofrequency Ablation in Human Medullary Thyroid Carcinoma.

INTRODUCTION: Currently, Medullary Thyroid Carcinoma (MTC) is considered a kind of rare neuroendocrine tumor, and molecular-targeted drugs have previously been used for MTC treatment. METHOD: However, the prognosis of MTC patients is still not significant. In the present work, we aimed to explore the antitumor activity of the molecularly targeted drug anlotinib in combination with radiofrequency ablation on MTC. RESULT: The targets of anlotinib were clearly expressed in MTC tissue specimens, and the expression level of these factors was much higher in MTC clinical specimens than in nontumor tissues. At the same time, anlotinib or Radiofrequency Ablation (RFA) showed clear antitumor activity against the MTC cell line TT (TT cells) and the tumor tissue it formed. Anlotinib, in combination with RFA, significantly increased the antitumor activity of RFA. CONCLUSION: These results indicated that the combination of anlotinib with radiofrequency ablation could be a promising therapeutic strategy for MTC treatment.

Incidence and risk factors of severe acute high-altitude illness in healthy adults first entering the northern Tibetan Plateau of over 5,000 m.

Background: Our study was designed to determine the incidence and risk factors of severe acute high-altitude illness (AHAI) in healthy adults first entering the northern Tibetan Plateau of over 5,000 m. Methods: In our prospective observational study, we enrolled 500 people who were scheduled for fast ascension to the northern Tibetan Plateau. The primary outcome variable was severe AHAI, defined as the presence of serious symptoms that could not be ameliorated by general treatment and required evacuation to lower altitudes. According to the inclusion and exclusion criteria, a cohort of 383 healthy people was included in the statistical analysis. We calculated the incidence of severe AHAI, identified the risk factors, and the differences in the most severe symptoms experienced. Results: Sixty-eight people were diagnosed with severe AHAI, and the incidence was 17.8%. Compared to individuals without severe AHAI, those with severe AHAI were more likely to be over the age of 40 years, of Han Chinese nationality, and living at an altitude of <1,500 m. They were less likely to belong to the Yi nationality, had a lower altitude of permanent residence, and exhibited decreased levels of lymphocyte count and hemoglobin concentration. Multivariable logistic regression showed that the mean altitude of permanent residence [per kilometer, adjusted odds ratio (AOR) = 0.464; 95% confidence interval (CI), 0.304-0.708; p < 0.001] and lymphocyte count (AOR = 0.606; 95% CI, 0.378-0.970; p = 0.037) were the independent risk factors. Headache and dyspnea ranked in the top two of the most severe symptoms for people with severe AHAI. Conclusion: Living at lower altitudes and having a decreased lymphocyte level were the risk factors of severe AHAI in healthy adults first entering the plateau of over 5,000 m.

Therapeutic efficacy of rituximab combined with cyclosporin A on B-cell dysregulation in chronic graft-versus-host disease.

OBJECTIVE: Chronic graft-versus-host disease (cGVHD) is a significant complication following allogenic hematopoietic stem cell transplantation, often necessitating therapeutic interventions such as rituximab (RTX) and cyclosporin A (CsA). This study aims to elucidate the mechanisms by which RTX and CsA jointly address B-cell dysregulation in cGVHD, providing a theoretical foundation and scientific rationale for the treatment and prognostic evaluation of this condition. METHODS: A total of 30 cGVHD mouse models were established by subjecting recipient mice to total body irradiation followed by injection of a mixed suspension of bone marrow cells and splenocytes from donor mice. From Day 2 to Day 29 post-model establishment, the mice received subcutaneous administration of RTX and CsA. Throughout the study, body weight, clinical cGVHD scores, and survival rates were monitored. Blood samples were collected via the orbital venous plexus. Serum levels of B-cell activating factor (BAFF) and pro-inflammatory factors were measured using enzyme-linked immunosorbent assay (ELISA), and the ratio of regulatory B cells (Bregs) in the blood sample was assessed via flow cytometry. RESULTS: Mice with cGVHD exhibited a 14.5% decrease in body weight, elevated clinical scores, and more severe symptoms compared to the control group. Notably, all mice in both the cGVHD and control groups survived until the conclusion of the study. Induction of cGVHD resulted in B-cell dysregulation, evidenced by elevated serum BAFF levels and a decreased proportion of Bregs. However, treatment with RTX combined with CsA ameliorated B-cell dysregulation and significantly reduced serum levels of pro-inflammatory factors in cGVHD mice, with decreases of 39.78% in TNF-α and 37.89% in IL-6. CONCLUSION: The combination of RTX and CsA effectively mitigates B-cell dysregulation in cGVHD, thereby reducing the severity and progression of the disease.

Machine learning risk prediction model for bloodstream infections related to totally implantable venous access ports in patients with cancer.

Objective: This study aimed to develop and validate a machine learning-based risk prediction model for catheter-related bloodstream infection (CRBSI) following implantation of totally implantable venous access ports (TIVAPs) in patients. Methods: A retrospective cohort study design was employed, utilizing the R software package mlr3. Various algorithms including logistic regression, naive Bayes, K nearest neighbor, classification tree, and random forest were applied. Addressing class imbalance, benchmarks were used, and model performance was assessed using the area under the curve (AUC). The final model, chosen for its superior performance, was interpreted using variable importance scores. Additionally, a nomogram was developed to calculate individualized risk probabilities, enhancing clinical utility. Results: The study involved 755 patients across both development and validation cohorts, with a TIVAP-CRBSI rate of 14.17%. The random forest model demonstrated the highest discrimination ability, achieving a validated AUC of 0.94, which was consistent in the validation cohort. Conclusions: This study successfully developed a robust predictive model for TIVAP-CRBSI risk post-implantation. Implementation of this model may aid healthcare providers in making informed decisions, thereby potentially improving patient outcomes.

Data acquisition system for a newly-built hard x-ray/soft gamma-ray spectrometer imaging system on experimental advanced superconducting tokamak.

A portable hard X-ray and soft gamma-ray spectrometer imaging system (HXS) has been constructed to gather physical information about fast electrons confined in the Experimental Advanced Superconducting Tokamak (EAST). The system is installed on the low field side of the mid-plane and provides a viewing field tangential to the toroidal field. The system utilizes a two-dimensional Cadmium Zinc Telluride (CdZnTe) semiconductor detector with 128 channels, and a data acquisition (DAQ) system has been designed for it. The DAQ system features a highly integrated signal processing system with the capability of high-speed processing and digital transmission of signals from 128 channels. In addition, a related DAQ software has been developed using a modular design approach, facilitating tasks such as data reception, storage, and preliminary processing. HXS, which has been applied during the recent EAST campaign, directly obtains the digital energy spectrum of incident photons. The DAQ system is described in detail in this paper. The hardware components and energy calibration have also been described. Experimental data have been successfully obtained and briefly discussed. More physical research will be reported in future publications.

Physiological Mechanisms by Which the Functional Ingredients in Beer Impact Human Health.

Nutritional therapy, for example through beer, is the best solution to human chronic diseases. In this article, we demonstrate the physiological mechanisms of the functional ingredients in beer with health-promoting effects, based on the PubMed, Google, CNKI, and ISI Web of Science databases, published from 1997 to 2024. Beer, a complex of barley malt and hops, is rich in functional ingredients. The health effects of beer against 26 chronic diseases are highly similar to those of barley due to the physiological mechanisms of polyphenols (phenolic acids, flavonoids), melatonin, minerals, bitter acids, vitamins, and peptides. Functional beer with low purine and high active ingredients made from pure barley malt, as well as an additional functional food, represents an important development direction, specifically, ginger beer, ginseng beer, and coix-lily beer, as consumed by our ancestors ca. 9000 years ago. Low-purine beer can be produced via enzymatic and biological degradation and adsorption of purines, as well as dandelion addition. Therefore, this review paper not only reveals the physiological mechanisms of beer in overcoming chronic human diseases, but also provides a scientific basis for the development of functional beer with health-promoting effects.

A predictive model for therapy failure in patients with chronic myeloid leukemia receiving tyrosine kinase inhibitor therapy.

ABSTRACT: Although tyrosine kinase inhibitor (TKI) therapy has markedly improved the survival of people with chronic-phase chronic myeloid leukemia (CML), 20% to 30% of people still experienced therapy failure. Data from 1955 consecutive patients with chronic-phase CML diagnosed by the European LeukemiaNet recommendations from 1 center receiving initial imatinib or a second-generation (2G) TKI therapy were interrogated to develop a clinical prediction model for TKI-therapy failure. This model was subsequently validated in 3454 patients from 76 other centers. Using the predictive clinical covariates associated with TKI-therapy failure, we developed a model that stratified patients into low-, intermediate- and high-risk subgroups with significantly different cumulative incidences of therapy failure (P < .001). There was good discrimination and calibration in the external validation data set, and the performance was consistent with that of the training data set. Our model had the better prediction discrimination than the Sokal and European Treatment and Outcome Study long-term survival scores, with the greater time-dependent area under the receiver-operator characteristic curve values and a better ability to redefine the risk of therapy failure. Our model could help physicians estimate the likelihood of initial imatinib or 2G TKI-therapy failure in people with chronic-phase CML.

Self-assembly of cascade nanoenzyme glucose oxidase encapsulated in copper benzenedicarboxylate for wearable sweat-glucose colorimetric sensors with smartphone readout.

BACKGROUND: With the advent of personalized medical approaches, precise and tailored treatments are expected to become widely accepted for the prevention and treatment of diabetes. Paper-based colorimetric sensors that function in combination with smartphones have been rapidly developed in recent years because it does not require additional equipment and is inexpensive and easy to perform. In this study, we developed a portable, low-cost, and wearable sweat-glucose detection device for in situ detection. RESULTS: The sensor adopted an integrated biomimetic nanoenzyme of glucose oxidase (GOx) encapsulated in copper 1, 4-benzenedicarboxylate (CuBDC) (GOx@CuBDC) through a biomimetic mineralization process. CuBDC exhibited a peroxide-like effect, cascade catalytic effect with the encapsulated GOx, and increased the enzyme stability. GOx@CuBDC and 3,3,5,5-tetramethylbenzidine were combined to form a hybrid membrane that achieved single-step paper-based glucose detection. SIGNIFICANCE AND NOVELTY: This GOx@CuBDC-based colorimetric glucose sensor was used to quantitatively analyze the sweat-glucose concentration with smartphone readings. The sensor exhibited a good linear relationship over the concentration range of 40-900 µM and a limit of detection of 20.7 µM (S/N = 3). Moreover, the sensor performed well in situ monitoring and in evaluating variations based on the consumption of foods with different glycemic indices. Therefore, the fabricated wearable sweat-glucose sensors exhibited optimal practical application performance.

Two new species of Ganoderma (Ganodermataceae, Basidiomycota) from Southwest China.

Ganoderma is a large and diverse genus containing fungi that cause white rot to infect a number of plant families. This study describes G.phyllanthicola and G.suae as new species from Southwest China, based on morphological and molecular evidence. Ganodermaphyllanthicola is characterized by dark brown to purplish black pileus surface with dense concentric furrows, pale yellow margin, irregular pileipellis cells, small pores (5-7 per mm) and ellipsoid to sub-globose basidiospores (8.5-10.0 × 6.0-7.5 µm). Ganodermasuae is characterized by reddish brown to oxblood red pileus surface and lead gray to greyish-white pore surface, heterogeneous context, wavy margin and almond-shaped to narrow ellipsoid basidiospores (8.0-10.5 × 5.0-7.0 µm). The phylogeny of Ganoderma is reconstructed with multi-gene sequences: the internal transcribed spacer region (ITS), the large subunit (nrLSU), translation elongation factor 1-α gene (TEF-1α) and the second subunit of RNA polymerase II (RPB2). The results show that G.suae and G.phyllanthicola formed two distinct line-ages within Ganoderma. Descriptions, illustrations and phylogenetic analyses results of the two new species are presented.

Liquid-Phase Adsorption Behavior of ß-D-Glucooligosaccharides When Using Activated Carbon for Separation, and the Antioxidant Stress Activity of Purified Fractions.

The adsorption characteristics of ß-glucooligosaccharides on activated carbon and the purification were systematically investigated. The maximum adsorption capacity of activated carbon reached 0.419 g/g in the optimal conditions. The adsorption behavior was described to be monolayer, spontaneous, and exothermic based on several models' fitting results. Five fractions with different degrees of polymerization (DPs) and structures of ß-glucooligosaccharides were obtained by gradient ethanol elution. 10E mainly contained disaccharides with dp2a (G1→6G) and dp2b (G1→3G). 20E possessed trisaccharides with dp3a (G1→6G1→3G) and dp3b (G1→3G1→3G). 30E mainly consisted of dp3a and dp4a (G1→3G1→3(G1→6)G), dp4b (G1→6G1→3G1→3G), and dp4c (G1→3G1→3G1→3G). In addition to tetrasaccharides, 40E and 50E also contained pentasaccharides and hexasaccharides with ß-(1→3)-linked or ß-(1→6)-linked glucose residues. All fractions could inhibit the accumulation of intracellular reactive oxygen species (ROS) in H2O2-induced Caco-2 cells, and they could improve oxidative stress damage by increasing the activity of superoxide dismutase (SOD) and reduced glutathione (GSH), which were related to their DPs and structures. 50E with high DPs showed better anti-oxidative stress activity.

Features and frequency of use of electronic health records in primary care across 20 countries: a cross-sectional study.

OBJECTIVES: Variation exists in the capabilities of electronic healthcare records (EHRs) systems and the frequency of their use by primary care physicians (PCPs) from different settings. We aimed to examine the factors associated with everyday EHRs use by PCPs, characterise the EHRs features available to PCPs, and to identify the impact of practice settings on feature availability. STUDY DESIGN: Cross-sectional study. METHODS: PCPs from 20 countries completed cross-sectional online survey between June and September 2020. Responses which reported frequency of EHRs use were retained. Associations between everyday EHRs use and PCP and practice factors (country, urbanicity, and digital maturity) were explored using multivariable logistic regression analyses. The effect of practice factors on the variation in availability of ten EHRs features was estimated using Cramer's V. RESULTS: Responses from 1520 out of 1605 PCPs surveyed (94·7%) were retained. Everyday EHRs use was reported by 91·2% of PCPs. Everyday EHRs use was associated with PCPs working >28 h per week, having more years of experience using EHRs, country of employment, and higher digital maturity. EHRs features concerning entering, and retrieving data were available to most PCPs. Few PCPs reported having access to tools for 'interactive patient education' (37·3%) or 'home monitoring and self-testing of chronic conditions' (34·3%). Country of practice was associated with availability of all EHRs features (Cramer's V range: 0·2-0·6), particularly with availability of tools enabling patient EHRs access (Cramer's V: 0·6, P < 0.0001). Greater feature availability of EHRs features was observed with greater digital maturity. CONCLUSIONS: EHRs features intended for patient use were uncommon across countries and levels of digital maturity. Systems-level research is necessary to identify the country-specific barriers impeding the implementation of EHRs features in primary care, particularly of EHRs features enabling patient interaction with EHRs, to develop strategies to improve systems-wide EHRs use.

Colorimetric aptasensor based on temporally controllable light-stimulated oxidase-mimicking fluorescein for the sensitive detection of exosomes in mild conditions.

Analysis of exosomes provides important information for rapid and non-invasive screening of tumors. However, sensitive and convenient detection of exosomes remains technically challenging to date. Herein, a colorimetric aptasensor based on the light-stimulated oxidase-mimicking activity of FITC was constructed for detecting ovarian cancer (OC) exosomes. The aptasensor contained an EpCAM aptamer to capture OC exosomes. Cholesterol and fluorescein (FITC) were used to modify either end of the DNA (DNA anchor). The DNA anchor could combine with exosomes through a hydrophobic reaction between cholesterol and the lipid membrane. FITC oxidized 3,3',5,5'-tetramethylbenzidine (TMB) under a 365 nm LED light source in a temporally controllable manner under mild conditions, causing the solution to change from colorless to blue, and the corresponding UV-vis absorbance increased. Based on this principle, the exosomes were qualitatively analyzed by observing the color change with the naked eye. In parallel, the exosome concentration was also detected using UV-vis spectrophotometry. The linear range was from 2 × 105 to 100 × 105 particles per mL with a limit of detection of 1.77 × 105 particles per mL. The developed aptasensor also exhibited favorable selectivity and could discriminate the exosomes from OC cells and normal cells. Besides, the receiver operating characteristic (ROC) curve demonstrates that it is possible to distinguish between patients with OC and healthy donors (HDs) using exosomes as the biomarker. Our technology may expand the applications of DNA-based detection method-enabled OC diagnostic tools.

Zuberitamab, an innovative anti-CD20 monoclonal antibody, for patients with primary immune thrombocytopenia in China: a randomized, double-blind, placebo-controlled, phase 2 study.

Background: Primary immune thrombocytopenia (ITP) is an autoimmune disease, and rituximab (RTX) induces long-term effect as second-line treatments. Zuberitamab is an innovative anti-CD20 monoclonal antibody, which was first developed in China and launched in diffuse large B lymphoma. This study aimed to investigate the safety, efficacy, and anticipated therapeutic dose of zuberitamab in Chinese ITP patients. Methods: This randomised, double-blind, placebo-controlled, phase 2 study was conducted at 26 hospitals in China. Eligible patients were aged 18-70 years, had primary immune thrombocytopenia for more than 6 months, and did not respond or relapsed after previous treatment and had a pre-treatment platelet count of <30 × 109/L. Patients randomly received zuberitamab in a dose escalation (100/300/600 mg) or placebo once-weekly for 4 weeks and followed up to 24 weeks. The primary endpoint is the proportion of patients with a platelet count ≥50 × 109/L at week 8. Secondary endpoints include the proportion of patients with platelet counts ≥50 × 109/L or ≥100 × 109/L at least once within week 12/24, the proportion of patients experiencing platelets increased twice more than baseline as well as ≥30 × 109/L at least once during the treatment. Adverse events, pharmacokinetic, B cell depletion and immunogenicity were also assessed. This study is registered with https://www.chictr.org.cn/as ChiCTR2100050513. Findings: From October 2021 to March 2023, 50 patients were screened for eligibility, of whom 32 patients were enrolled and randomly assigned to placebo (n = 4), zuberitamab 100 mg (n = 10), 300 mg (n = 8) and 600 mg (n = 10) groups. The primary endpoint (PLT ≥50 × 109/L at week 8) was achieved by 40% of patients in the 100 mg group, while none in the other groups. Within 12 weeks, the proportions of patients in each treatment group achieving at least one instance of platelet count ≥50 × 109/L or ≥100 × 109/L or an increase twice more than baseline as well as ≥30 × 109/L were (70%, 38%, 50%), (60%, 13%, 30%), and (80%, 50%, 70%) in zuberitamab 100/300/600 mg groups, respectively. By week 24, the proportions of patients achieving these secondary endpoints remained relatively stable or showed a mild increase of around 10%. The anticipated therapeutic dose of zuberitamab was 100 mg. The plasma concentration of zuberitamab showed an increasing trend with dose (100 mg-600 mg) and linear pharmacokinetic behavior. CD19+ B cells and CD20+ B lymphocytes rapidly declined to 0% within one week and consistently maintained reduced levels throughout the entire treatment phase in three groups. Adverse events occurred in all patients with most of them were mild to moderate, no severe infections occurred. A slight decrease in immunoglobulins was observed in the 600 mg group, but gradually recovered at week 20. Three patients (2 in 100 mg and 1 in 600 mg group) were tested positive for anti-zuberitamab antibodies. We also observed that women, disease duration <12 months, and MAIPA + patients may have higher response rates. Interpretation: This study preliminarily confirmed that 100 mg zuberitamab was safe and effective in treating ITP and was recommended to support further investigation. Funding: National Natural Science Foundation of China and Zhejiang Bioray Biopharmaceutical Co. Ltd.

Manganese induces podocyte injury through regulating MTDH/ALKBH5/NLRP10 axis: Combined analysis at epidemiology and molecular biology levels.

Manganese (Mn) is an essential micronutrient required for various biological processes but excess exposure to Mn can cause neurotoxicity. However, there are few reports regarding the toxicity effect of Mn on the kidney as well as the underlying molecule mechanism. Herein, in vivo experiments were adopted to assess the toxicity effects associated with Mn, and found that chronic Mn treatment induced the injury of glomerular podocytes but not renal tubule in rats. Genome-wide CRISPR/Cas9 knockout screen was then employed to explore the biotargets of the toxic effect of Mn on podocytes. Through functional analyses of the enriched candidate genes, NLRP10 was found to be significantly up-regulated and mediated Mn-induced podocyte apoptosis. Further mechanism investigation revealed that NLRP10 expression was regulated by demethylase AlkB homolog 5 (ALKBH5) in an m6A-dependent fashion upon Mn treatment. Moreover, Mn could directly bind to Metadherin (MTDH) and promoted its combination with ALKBH5 to promote NLRP10 expression and cell apoptosis. Finally, logistic regressions, restricted cubic spline regressions and uniform cubic B-spline were used to investigate the association between Mn exposure and the risk of chronic kidney disease (CKD). A U-shaped nonlinear relationship between CKD risk and plasma Mn level, and a positive linear relationship between CKD risk and urinary Mn levels was found in our case-control study. To sum up, our findings illustrated that m6A-dependent NLRP10 regulation is indispensable for podocyte apoptosis and nephrotoxicity induced by Mn, providing fresh insight into understanding the health risk of Mn and a novel target for preventing renal injury in Mn-intoxicated patients.

Sensor Head Temperature Distribution Reconstruction of High-Precision Gravitational Reference Sensors with Machine Learning.

Temperature fluctuations affect the performance of high-precision gravitational reference sensors. Due to the limited space and the complex interrelations among sensors, it is not feasible to directly measure the temperatures of sensor heads using temperature sensors. Hence, a high-accuracy interpolation method is essential for reconstructing the surface temperature of sensor heads. In this study, we utilized XGBoost-LSTM for sensor head temperature reconstruction, and we analyzed the performance of this method under two simulation scenarios: ground-based and on-orbit. The findings demonstrate that our method achieves a precision that is two orders of magnitude higher than that of conventional interpolation methods and one order of magnitude higher than that of a BP neural network. Additionally, it exhibits remarkable stability and robustness. The reconstruction accuracy of this method meets the requirements for the key payload temperature control precision specified by the Taiji Program, providing data support for subsequent tasks in thermal noise modeling and subtraction.

The protective effect and mechanism of glycosides of cistanche deserticola on rats in middle cerebral artery occlusion (MCAO) model.

Cerebral ischemia-reperfusion injury (CIRI) occurs frequently clinically as a complication following cardiovascular resuscitation resulting in neuronal damage specifically to the hippocampal CA1 region with consequent cognitive impairment. Apoptosis and oxidative stress were proposed as major risk factors associated with CIRI development. Previously, glycosides obtained from Cistanche deserticola (CGs) were shown to play a key role in counteracting CIRI; however, the underlying mechanisms remain to be determined. This study aimed to investigate the neuroprotective effect of CGs on subsequent CIRI in rats. The model of CIRI was established for 2 hr and reperfusion for 24 hr by middle cerebral artery occlusion (MCAO) model. The MCAO rats were used to measure the antioxidant and anti-apoptotic effects of CGs on CIRI. Neurological function was evaluated by the Longa neurological function score test. 2,3,5-Triphenyltetrazolium chloride (TTC) staining was used to detect the area of cerebral infarction. Nissl staining was employed to observe neuronal morphology. TUNEL staining was used to detect neuronal apoptosis, while Western blot determined protein expression levels of factors for apoptosis-related and PI3K/AKT/Nrf2 signaling pathway. Data demonstrated that CGs treatment improved behavioral performance, brain injury, and enhanced antioxidant and anti-apoptosis in CIRI rats. In addition, CGs induced activation of PI3K/AKT/Nrf2 signaling pathway accompanied by inhibition of the expression of apoptosis-related factors. Evidence indicates that CGs amelioration of CIRI involves activation of the PI3K/AKT/Nrf2 signaling pathway associated with increased cellular viability suggesting these glycosides may be considered as an alternative compound for CIRI treatment.

Magnetism and electronic properties of ConMoP (n = 1 ~ 5) cluster: a DFT study.

CONTEXT: Hydrogen has emerged as a promising clean energy carrier, underscoring the imperative need to comprehend its adsorption mechanisms. This study delves into the magnetic and electronic properties of Co-Mo-P clusters, aiming to unveil their catalytic potential in hydrogen production. Employing density functional theory (DFT), we optimized cluster configurations and scrutinized their magnetic behaviors. Our investigation unveiled 16 stable configurations of the ConMoP (n = 1 ~ 5) cluster, predominantly in steric forms. The magnetic attributes were primarily ascribed to the d orbitals of Co metal atoms, with Co3MoP exhibiting exceptional magnetic characteristics. Analysis of density of state diagrams revealed the prevalence of spin-up α-electrons in d orbitals, while spin-down ß-electrons attenuated overall magnetic properties. Localized orbital (LOL) analysis highlighted stable covalent bonds within the clusters, affirming their catalytic potential. Orbital delocalization index (ODI) analysis revealed diverse spatial distribution ranges for orbitals across different configurations, suggesting a progressive attenuation of off-domain properties with increasing cluster size. Furthermore, infrared spectroscopy unveiled distinct vibrational peaks in various configurations, indicative of unique infrared activities. These findings contribute to a nuanced theoretical understanding of Co-Mo-P clusters and pave the path for future research aimed at augmenting their catalytic efficiency in hydrogen production. This study underscores the viability of Co-Mo-P clusters as alternatives to conventional Pt catalysts, offering insights into the design of novel materials for sustainable energy applications. Further research is warranted to explore the behavior of the Co-Mo-P system under diverse reaction conditions, fostering advancements in materials and energy science. METHODS: In this study, we harnessed the ConMoP (n = 1 ~ 5) cluster as a simulation platform for probing the local structure of the material. Our aim was to scrutinize the magnetism, electronic characteristics influenced by the varying metal atoms within these clusters. A systematic exploration involved incrementing the number of metal atoms and expanding the cluster size to elucidate the corresponding property variations. Density functional theory (DFT) calculations were pivotal to our methodology, employing the B3LYP hybrid functional implemented in the Gaussian 16 software package. The ConMoP (n = 1 ~ 5) cluster underwent optimization calculations and vibrational analysis at the def2-tzvp quantization level, yielding optimized configurations with diverse spin multiplet degrees. To comprehensively characterize and visually represent the stability, electronic features, and catalytic attributes of these configurations, we employed a suite of computational tools. Specifically, quantum chemistry software GaussView and wave function analysis software Multiwfn played integral roles. Through the integrated use of these computational tools, we acquired valuable insights into the magnetism, electronic characteristics of the ConMoP (n = 1 ~ 5) cluster, shedding light on their dependency on distinct metal atoms.