Ten Thousand Recaptures of a Single DNA Molecule in a Nanopore and Variance Reduction of Translocation Characteristics.

Nanopores have emerged as highly sensitive biosensors operating at the single-molecule level. However, the majority of nanopore experiments still rely on averaging signals from multiple molecules, introducing systematic errors. To overcome this limitation and obtain accurate information from a single molecule, the molecular ping-pong methodology provides a precise approach involving repeated captures of a single molecule. In this study, we have enhanced the molecular ping-pong technique by incorporating a customized electronic system and control algorithm, resulting in a recapture number exceeding 10,000. During the ping-pong process, we observed a significant reduction in the variance of translocation characteristics, providing fresh insights into single-molecule translocation dynamics. An inhomogeneous translocation velocity of folded DNA has been revealed, illustrating a strong interaction between the molecule and the solid-state nanopore. The results not only promise heightened experimental efficiency with reduced sample volume but also increase the precision in statistical analysis of translocation events, marking a significant stride toward authentic single-molecule nanopore sensing.

Genomic biology and therapeutic strategies of liver metastasis from gastric cancer.

The liver is a frequent site of metastasis in advanced gastric cancer (GC). Despite significant advancements in diagnostic and therapeutic techniques, the overall survival rate for patients afflicted with gastric cancer liver metastasis (GCLM) remains dismally low. Precision oncology has made significant progress in identifying therapeutic targets and enhancing our understanding of metastasis mechanisms through genome sequencing and molecular characterization. Therefore, it is crucial to have a comprehensive understanding of the various molecular processes involved in GCLM and the fundamental principles of systemic therapy to develop new treatment approaches. This paper aims to review recent findings on the diagnosis, potential biomarkers, and therapies targeting the multiple molecular processes of GCLM, with the goal of improving treatment strategies for patients with GCLM.

Enhanced catalytic performance through a single-atom preparation approach: a review on ruthenium-based catalysts.

The outstanding catalytic properties of single-atom catalysts (SACs) stem from the maximum atom utilization and unique quantum size effects, leading to ever-increasing research interest in SACs in recent years. Ru-based SACs, which have shown excellent catalytic activity and selectivity, have been brought to the frontier of the research field due to their lower cost compared with other noble catalysts. The synthetic approaches for preparing Ru SACs are rather diverse in the open literature, covering a wide range of applications. In this review paper, we attempt to disclose the synthetic approaches for Ru-based SACs developed in the most recent years, such as defect engineering, coordination design, ion exchange, the dipping method, and electrochemical deposition etc., and discuss their representative applications in both electrochemical and organic reaction fields, with typical application examples given of: Li-CO2 batteries, N2 reduction, water splitting and oxidation of benzyl alcohols. The mechanisms behind their enhanced catalytic performance are discussed and their structure-property relationships are revealed in this review. Finally, future prospects and remaining unsolved issues with Ru SACs are also discussed so that a roadmap for the further development of Ru SACs is established.

Se-Elemental Concentration Gradient Regulation for Efficient Sb2(S,Se)3 Solar Cells with High Open-Circuit Voltages.

Antimony selenosulfide (Sb2(S,Se)3), featuring large absorption coefficient, excellent crystal structure stability, benign non-toxic characteristic, outstanding humidity and ultraviolet tolerability, has recently attracted enormous attention and research interest regarding its photoelectric conversion properties. However, the open-circuit voltage (Voc) for Sb2(S,Se)3-based photovoltaic devices is relatively low, especially for the device with a high power conversion efficiency (η). Herein, an innovative Se-elemental concentration gradient regulation strategy has been exploited to produce high-quality Sb2(S,Se)3 films on TiO2/CdS substrates through a thioacetamide(TA)-synergistic dual-sulfur source hydrothermal-processed method. The Se-elemental gradient distribution produces a favorable energy band structure, which suppresses the energy level barriers for hole transport and enhances the driving force for electron transport in Sb2(S,Se)3 film. This facilitates efficient charge transport/separation of photogenerated carriers and boosts significantly the Voc of Sb2(S,Se)3 photovoltaic devices. The champion TA-Sb2(S,Se)3 planar heterojunction (PHJ) solar cell displays an considerable η of 9.28% accompanied by an exciting Voc rising to 0.70 V that is currently the highest among Sb2(S,Se)3-based solar cells with efficiencies exceeding 9.0%. This research is anticipated to contribute to the preparation of high-quality Sb2(S,Se)3 thin film and the achievement of efficient inorganic Sb2(S,Se)3 PHJ photovoltaic device.

Cooling Condition Effect on Spectral Properties and Smartphone-Based Anticounterfeiting Application of Zn3Ga2Ge2O10/Cr3+ Phosphors.

The influence of cooling history for the Zn3Ga2Ge2O10/Cr3+ phosphors prepared by solid state reaction on the spectral properties was discovered, and an anticounterfeiting scheme based on the identification with smartphone was proposed and experimentally demonstrated using the studied phosphors. A combination of color-tunable visible fluorescence emission and near-infrared (NIR) afterglow emission in Zn3Ga2Ge2O10/x mol % Cr3+(x = 0, 0.05, 1, 2, 3, and 4) phosphors to achieve multimode anticounterfeiting was reported. It is found that with the increasing Cr3+ concentrations, the visible emission can be tuned from green, light pink, and light red to deep red under 254 nm ultraviolet (UV) excitation. This phenomenon is related to the formation of oxygen vacancies in the host during the process of natural cooling and the characteristic emission of Cr3+. In addition, the persistent time of the Cr3+ emission centered at 700 nm can be also tuned by various Cr3+ concentrations. A possible mechanism was deduced to explain the afterglow phenomenon. Lastly, a flower pattern applied in anticounterfeiting was fabricated using the Zn3Ga2Ge2O10/x mol % Cr3+ (x = 0, 0.05, 1, 2, 3, and 4) phosphors to present tunable color and NIR afterglow signals at different excitation modes, and the camera of smartphone was chosen as a detection tool to take the NIR images. The results obtained above suggest that the prepared phosphors at natural cooling condition have great potential in affording advanced optical anticounterfeiting.

Estimating the global prevalence of secondary hyperparathyroidism in patients with chronic kidney disease.

Background: Chronic kidney disease (CKD)-related secondary hyperparathyroidism (SHPT) is associated with higher morbidity and death. The goal of this study was to mine the SHPT data already available to do a meta-analysis on the global prevalence of SHPT caused by CKD. Methods: Embase, Medline, Web of Science, Cochrane Central Databases, and Google Scholar were searched to identify studies on the prevalence of SHPT due to CKD from inception to November 2023. Pooled prevalence was calculated using the DerSimonian-Laird random effects model with a logit transformation. Results: Twenty-one eligible studies involving 110977 patients were included. Our results revealed that the estimated global prevalence of SHPT due to CKD was 49.5% (95% CI 30.20-68.18), regardless of the diagnostic criteria. For subgroup analysis, Southern Asia (84.36%, 95% CI 79.35-88.34) had a significantly higher SHPT prevalence than other geographic regions. SHPT due to CKD was most prevalent in China (85.14%, 95% CI 81.74-88.00). Conclusions: SHPT due to CKD is highly prevalent. This necessitates awareness and therapeutic approaches from primary care physicians, medical professionals, and health strategy authorities. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO, identifier CRD42024514007.

Surface activation via selective dealloying of Cu-based metallic glasses for efficient catalytic behavior.

Surface activation is considered to regulate the electronic structures of materials for enhancing catalytic capability. Herein, we report a controllable strategy for constructing three-dimensional micro-nanoporous copper catalysts with high reactivity and activity for the degradation reaction of organic pollutants. Various micro-nanoporous structures and in situ formation processes by chemical selective dealloying of Cu-based metallic glasses are evaluated due to the surface modification. The porous catalysts exhibit superior catalytic performance, attributing to the catalytic mechanisms related to the superior surface activity of nanoscale copper composites and the strong oxidizing capability of activated radicals. These findings will provide a promising synthesis approach for three-dimensional micro-nanoporous catalysts for many chemical reactions.

Highly Crystalline Multivariate Prussian Blue Analogs via Equilibrium Chelation Strategy for Stable and Fast Charging Sodium-Ion Batteries.

Prussian blue analogs (PBAs) have been widely recognized as superior cathode materials for sodium-ion batteries (SIBs) owing to numerous merits. However, originating from the rapid crystal growth, PBAs still suffer from considerable vacancy defects and interstitial water, making the preparation of long-cycle-life PBAs the greatest challenge for its practical application. Herein, a novel equilibrium chelation strategy is first proposed to synthesize a high crystallinity (94.7%) PBAs, which is realized by modulating the chelating potency of strong chelating agents via "acid effect" to achieve a moderate chelating effect, forcefully breaking through the bottleneck of poor cyclic stability for PBAs cathodes. Impressively, the as-prepared highly crystalline PBAs represent an unprecedented level of electrochemical performance including ultra-long lifespan (10000 cycles with 86.32% capacity maintenance at 6 A g-1), excellent rate capability (82.0 mAh g-1 at 6 A g-1). Meanwhile, by pairing with commercial hard carbon, the as-prepared PBAs-based SIBs exhibit high energy density (350 Wh kg-1) and excellent capacity retention (82.4% after 1500 cycles), highlighting its promising potential for large-scale energy storage applications.

POLR1D silencing suppresses lung cancer cells proliferation and migration via inhibition of PI3K-Akt pathway.

AIM: The most common type of cancer that leads to death worldwide is lung cancer. Despite significant surgery and chemotherapy improvements, lung cancer patient's survival rate is still poor. The RNA polymerase I subunit D (POLR1D) gene can induce various cancers. A current study reported that POLR1D plays a vital role in cancer prognosis. However, its biological function in the development of lung cancer remains unclear. METHODS: Reverse transcription PCR (RT-PCR) measured the relative POLR1D protein expression level in lung cancer cell lines. Lung cancer cell proliferation, migration, and invasion were analyzed by performing cell counting kit-8 (CCK-8), and transwell. The phosphatidylinositol 3-kinase/serine-threonine kinase (PI3K/AKT) signaling pathway-related protein expressions were examined by Western blotting assay. RESULTS: POLR1D protein expression was elevated in lung cancer. Lung cancer cell loss-of-function tests showed that POLR1D silencing could attenuate cell viability both in SK-MES-1 and in H2170 cells. Furthermore, silencing POLR1D inhibited SK-MES-1 and H2170 cells proliferation, migration, and invasion. Moreover, SK-MES-1 and H2170 cells' migration and invasion capacity were potentially suppressed by the knockdown of POLR1D. The progression of multiple cancers has been implicated in the PI3K/AKT pathway. Here, we observed that POLR1D silencing suppressed lung cancer progression by inhibition of the PI3K-Akt pathway. CONCLUSIONS: The study speculated that POLR1D might provide a new potential therapeutic possibility for treating lung cancer patients via targeting PI3K/AKT.

Chinese Herbal Medicine Combined With Liuzijue Exercise in Physiological Rehabilitation After Video-assisted Lung Lobectomy for Cancer: A Prospective Propensity Score Matching Study.

OBJECTIVE: To observe the clinical efficacy of Chinese herbal medicine combined with Liuzijue exercise on the physiological symptoms and quality of life (QoL) in postoperative patients with early-stage lung cancer. METHODS: One hundred and eighty-three lung cancer patients who underwent video-assisted thoracoscopic surgery (VATS) were categorize into either a traditional Chinese medicine treatment group (CM) or a control group (non-traditional Chinese medicine treatment, NC), among whom 73 underwent Chinese herbal medicine and Liuzijue therapy, while 110 underwent no comprehensive treatment with traditional Chinese medicine. The propensity score matching (PSM) method with a 1:2 ratio was used to balance the baseline characteristics and evaluate the efficacy of CM in improving postoperative symptoms and QoL. RESULTS: Cough, dyspnea, chest pain, and fatigue were the most common clinical symptoms after VATS. Except for chest pain, they were all correlated with the scope of operation (P < .05). After PSM, 165 patients were identified in the matched cohort, and the covariates of gender, age, operative site, and scope of operation were balanced between the 2 groups (P > .05). In the domain of global health status, the improvement in QoL in CM was greater than that in NC (6.06 ± 15.83 vs -1.06 ± 14.68, P = .005). In terms of symptoms, improvements in cough (1.69 ± 3.15 vs 0.38 ± 2.63, P = .006), dyspnea during climbing stairs (-10.30 ± 16.82 vs -1.82 ± 17.97, P = .004), and pain (-0.76 ± 1.32 vs -0.08 ± 1.31, P = .002) in CM were better than in NC. CONCLUSION: Comprehensive treatment with traditional Chinese medicine (TCM) can provide therapeutic benefits in physiological rehabilitation after VATS for cancer.

Gut Dysbiosis Drives Inflammatory Bowel Disease Through the CCL4L2-VSIR Axis in Glycogen Storage Disease.

Patients with glycogen storage disease type Ib (GSD-Ib) frequently have inflammatory bowel disease (IBD). however, the underlying etiology remains unclear. Herein, this study finds that digestive symptoms are commonly observed in patients with GSD-Ib, presenting as single or multiple scattered deep round ulcers, inflammatory pseudo-polyps, obstructions, and strictures, which differ substantially from those in typical IBD. Distinct microbiota profiling and single-cell clustering of colonic mucosae in patients with GSD are conducted. Heterogeneous oral pathogenic enteric outgrowth induced by GSD is a potent inducer of gut microbiota immaturity and colonic macrophage accumulation. Specifically, a unique population of macrophages with high CCL4L2 expression is identified in response to pathogenic bacteria in the intestine. Hyper-activation of the CCL4L2-VSIR axis leads to increased expression of AGR2 and ZG16 in epithelial cells, which mediates the unique progression of IBD in GSD-Ib. Collectively, the microbiota-driven pathomechanism of IBD is demonstrated in GSD-Ib and revealed the active role of the CCL4L2-VSIR axis in the interaction between the microbiota and colonic mucosal immunity. Thus, targeting gut dysbiosis and/or the CCL4L2-VISR axis may represent a potential therapy for GSD-associated IBD.

Hydrogen-bond tuned conjugated architectures for nitric oxide sensing in single-benzene framework: Advances and mechanistic insights.

In contrast to the conventional fluorescence enhancement resulting from the cessation of the photoinduced electron transfer effect upon capturing nitric oxide (NO) by o-phenylenediamine, we found an interesting fluorescence quench within small molecule fluorophores characterized by intramolecular hydrogen bonding. Herein, the integration of a push-pull electron system with intramolecular hydrogen bonding onto an ultra-small fluorophore was employed to fabricate a hydrogen bond-tuned single benzene core fluorescent probe with an exceptional fluorescence quantum yield of 26 %, denoted as HSC-1. By virtue of its small size and low molecular weight (mere 192 g/mol), it demonstrated superior solubility and biocompatibility. Given the optimized conditions, HSC-1 manifested extraordinary linearity in detecting NO concentrations ranging from 0.5 to 60 µM, with an outstanding detection limit of 23.8 nM. Theoretical calculations unraveled the photophysical properties of hydrogen bonding-related probe molecules and highlighted the NO sensing mechanism. This pioneering work offers an important platform for the design of small fluorescence probes only with a single benzene core applied to NO sensing, which will potentially emerge as a new frontier in the area.

QiDongNing induces lung cancer cell apoptosis via triggering P53/DRP1-mediated mitochondrial fission.

Non-small-cell lung cancer (NSCLC) is a major cause of worldwide cancer death, posing a challenge for effective treatment. Our previous findings showed that Chinese herbal medicine (CHM) QiDongNing (QDN) could upregulate the expression of p53 and trigger cell apoptosis in NSCLC. Here, our objective was to investigate the mechanisms of QDN-induced apoptosis enhancement. We chose A549 and NCI-H460 cells for validation in vitro, and LLC cells were applied to form a subcutaneous transplantation tumour model for validation in more depth. Our findings indicated that QDN inhibited multiple biological behaviours, including cell proliferation, cloning, migration, invasion and induction of apoptosis. We further discovered that QDN increased the pro-apoptotic BAX while inhibiting the anti-apoptotic Bcl2. QDN therapy led to a decline in adenosine triphosphate (ATP) and a rise in reactive oxygen species (ROS). Furthermore, QDN elevated the levels of the tumour suppressor p53 and the mitochondrial division factor DRP1 and FIS1, and decreased the mitochondrial fusion molecules MFN1, MFN2, and OPA1. The results were further verified by rescue experiments, the p53 inhibitor Pifithrin-α and the mitochondrial division inhibitor Mdivi1 partially inhibited QDN-induced apoptosis and mitochondrial dysfunction, whereas overexpression of p53 rather increased the efficacy of the therapy. Additionally, QDN inhibited tumour growth with acceptable safety in vivo. In conclusion, QDN induced apoptosis via triggering p53/DRP1-mediated mitochondrial fission in NSCLC cells.

Comparison of the therapeutic effects of mesenchymal stem cells derived from human dental pulp (DP), adipose tissue (AD), placental amniotic membrane (PM), and umbilical cord (UC) on postmenopausal osteoporosis.

Background: Osteoporosis is a systemic bone disease characterized by bone loss and microstructural degeneration. Recent preclinical and clinical trials have further demonstrated that the transplantation of mesenchymal stem cells (MSCs) derived from human adipose tissue (AD), dental pulp (DP), placental amniotic membrane (AM), and umbilical cord (UC) tissues can serve as an effective form of cell therapy for osteoporosis. However, MSC-mediated osteoimmunology and the ability of these cells to regulate osteoclast-osteoblast differentiation varies markedly among different types of MSCs. Methods: In this study, we investigated whether transplanted allogeneic MSCs derived from AD, DP, AM, and UC tissues were able to prevent osteoporosis in an ovariectomy (OVX)-induced mouse model of osteoporosis. The homing and immunomodulatory ability of these cells as well as their effects on osteoblastogenesis and the maintenance of bone formation were compared for four types of MSCs to determine the ideal source of MSCs for the cell therapy-based treatment of OVX-induced osteoporosis. The bone formation and bone resorption ability of these four types of MSCs were analyzed using micro-computed tomography analyses and histological staining. In addition, cytokine array-based analyses of serological markers and bioluminescence imaging assays were employed to evaluate cell survival and homing efficiency. Immune regulation was determined by flow cytometer assay to reflect the mechanisms of osteoporosis treatment. Conclusion: These analyses demonstrated that MSCs isolated from different tissues have the capacity to treat osteoporosis when transplanted in vivo. Importantly, DP-MSCs infusion was able to maintain trabecular bone mass more efficiently with corresponding improvements in trabecular bone volume, mineral density, number, and separation. Among the tested MSC types, DP-MSCs were also found to exhibit greater immunoregulatory capabilities, regulating the Th17/Treg and M1/M2 ratios. These data thus suggest that DP-MSCs may represent an effective tool for the treatment of osteoporosis.

Small particles, big effects: How nanoparticles can enhance plant growth in favorable and harsh conditions.

By 2050, the global population is projected to reach 9 billion, underscoring the imperative for innovative solutions to increase grain yield and enhance food security. Nanotechnology has emerged as a powerful tool, providing unique solutions to this challenge. Nanoparticles (NPs) can improve plant growth and nutrition under normal conditions through their high surface-to-volume ratio and unique physical and chemical properties. Moreover, they can be used to monitor crop health status and augment plant resilience against abiotic stresses (such as salinity, drought, heavy metals, and extreme temperatures) that endanger global agriculture. Application of NPs can enhance stress tolerance mechanisms in plants, minimizing potential yield losses and underscoring the potential of NPs to raise crop yield and quality. This review highlights the need for a comprehensive exploration of the environmental implications and safety of nanomaterials and provides valuable guidelines for researchers, policymakers, and agricultural practitioners. With thoughtful stewardship, nanotechnology holds immense promise in shaping environmentally sustainable agriculture amid escalating environmental challenges.

Luminescence properties and Judd-Ofelt analysis of Tb3+ doped Sr2YTaO6 double perovskite phosphors for white LED applications.

A series of Tb3+-doped Sr2YTaO6 double perovskite phosphors (SYT:Tb3+) were synthesized using a conventional solid-state reaction method. A strong green emission was observed in the SYT:Tb3+ phosphors, and the optimal doping concentration of Tb3+ was confirmed to be 5 mol%. The electric dipole-dipole interaction was ascribed to be the main mechanism for the luminescence concentration quenching. Analysis of the concentration-dependent fluorescence decay confirmed that the self-generated quenching model holds for the dynamic process of Tb3+ decays in SYT. Furthermore, the internal quantum efficiencies, non-radiative transition rates, and energy transfer rates of the 5D4 level for the SYT:Tb3+ samples were estimated, respectively. The luminescence thermal stability of the sample was also evaluated based on the Arrhenius model. The chromaticity shift of the SYT:5 mol% Tb3+ phosphor was examined to be 0.013 when the sample temperature was increased from 303 to 483 K, thus indicating excellent chromaticity shifting resistance under high temperature conditions. Moreover, the Judd-Ofelt parameters were calculated from the emission spectra of SYT:Tb3+ to be Ω2 = 0.29 × 10-20, Ω4 = 0.45 × 10-20, and Ω6 = 0.72 × 10-20 cm2, respectively. The fluorescence branching ratios and radiative transition rates for the 5D4 level were calculated based on the obtained Judd-Ofelt parameters. Finally, a white light-emitting diode (LED) prototype was assembled using a 310 nm LED chip combined with a prepared green SYT:Tb3+ phosphor and two other commercial blue and red phosphors. The obtained warm white light exhibits good chromaticity coordinates (0.32, 0.32) and a high color rendering index of 96.1. Based on the above results, it can be known that the prepared SYT:Tb3+ phosphors have a potential application as green emitting phosphors in white LEDs.

Clinical Efficacy and Gut Microbiota Regulating-Related Effect of Si-Jun-Zi Decoction in Postoperative Non-Small Cell Lung Cancer Patients: A Prospective Observational Study.

BACKGROUND: Postoperative non-small cell lung cancer (NSCLC) patients frequently encounter a deteriorated quality of life (QOL), disturbed immune response, and disordered homeostasis. Si-Jun-Zi Decoction (SJZD), a well-known traditional Chinese herbal formula, is frequently employed in clinical application for many years. Exploration is underway to investigate the potential therapeutic effect of SJZD for treating postoperative NSCLC. OBJECTIVE: To assess the efficacy of SJZD on QOLs, hematological parameters, and regulations of gut microbiota in postoperative NSCLC patients. METHODS: A prospective observational cohort study was conducted, enrolling 65 postoperative NSCLC patients between May 10, 2020 and March 15, 2021 in Yueyang Hospital, with 33 patients in SJZD group and 32 patients in control (CON) group. The SJZD group comprised of patients who received standard treatments and the SJZD decoction, while the CON group consisted of those only underwent standard treatments. The treatment period was 4 weeks. The primary outcome was QOL. The secondary outcomes involved serum immune cell and inflammation factor levels, safety, and alterations in gut microbiota. RESULTS: SJZD group showed significant enhancements in cognitive functioning (P = .048) at week 1 and physical functioning (P = .019) at week 4. Lung cancer-specific symptoms included dyspnea (P = .001), coughing (P = .008), hemoptysis (P = .034), peripheral neuropathy (P = .019), and pain (arm or shoulder, P = .020, other parts, P = .019) eased significantly in the fourth week. Anemia indicators such as red blood cell count (P = .003 at week 1, P = .029 at week 4) and hemoglobin (P = .016 at week 1, P = .048 at week 4) were significantly elevated by SJZD. SJZD upregulated blood cell cluster differentiation (CD)3+ (P = .001 at week 1, P < .001 at week 4), CD3+CD4+ (P = .012 at week 1), CD3+CD8+ (P = .027 at week 1), CD19+ (P = .003 at week 4), increased anti-inflammatory interleukin (IL)-10 (P = .004 at week 1, P = .003 at week 4), and decreased pro-inflammatory IL-8 (P = .004 at week 1, p = .005 at week 4). Analysis of gut microbiota indicated that SJZD had a significant impact on increasing microbial abundance and diversity, enriching probiotic microbes, and regulating microbial biological functions. CONCLUSIONS: SJZD appears to be an effective and safe treatment for postoperative NSCLC patients. As a preliminary observational study, this study provides a foundation for further research.

Predicting the mechanism of action of YQYYJD prescription in the treatment of non-small cell lung cancer using transcriptomics analysis.

ETHNOPHARMACOLOGICAL RELEVANCE: The efficacy of the herbal formula Yiqi Yangyin Jiedu (YQYYJD) in the treatment of advanced lung cancer has been reported in clinical trials. However, the key anti-lung cancer herbs and molecular mechanisms underlying its inhibition of lung cancer are not well-understood. AIM OF THE STUDY: To identify the key anti-lung cancer herbs in the YQYYJD formula and investigate their therapeutic effect and potential mechanism of action in non-small cell lung cancer (NSCLC) using transcriptomics and bioinformatics techniques. MATERIALS AND METHODS: A mouse Lewis lung carcinoma (LLC) subcutaneous inhibitory tumor model was established with 6 mice in each group. Mice were treated with the YQYYJD split formula: Yiqi Formula (YQ), Yangyin Formula (YY), and Ruanjian Jiedu Formula (RJJD) for 14 days. The tumor volume and mouse weight were recorded, and the status of tumor occurrence was further observed by taking photos. The tumor was stained with hematoxylin-eosin to observe its histopathological changes. Immunohistochemistry was used to detect the expression of the proliferation marker Ki67 and the apoptotic marker Caspase-3 in tumor tissues. Flow cytometry was used to detect the number of CD4+ and CD8+ T cells and cytokines interleukin-2 (IL-2) and interferon-gamma (IFN-γ) in the spleen and tumor tissues. The differential genes of key drugs against tumors were obtained by transcriptome sequencing of tumors. Gene Ontology (GO) and Kyoto Encyclopedia of Gene and Genomes (KEGG) enrichment analyses were performed on differential genes to obtain pathways and biological processes where targets were aggregated. TIMER2.0 and TISIDB databases were used to evaluate the impact of drugs on immune cell infiltration and immune-related genes. The binding activity of the key targets and compounds was verified by molecular docking. RESULTS: YQ, YY, and RJJD inhibited the growth of subcutaneous transplanted tumors in LLC mice to varying degrees and achieved antitumor effects by inhibiting the expression of tumor cell proliferation, apoptosis, and metastasis-related proteins. Among the three disassembled prescriptions, YQ better inhibited the growth of subcutaneous transplanted tumors in LLC mice, significantly promoted tumor necrosis, significantly increased the expression of Caspase-3 protein in tumor tissue, and significantly decreased the expression of Ki-67 (P < 0.05), thereby increasing the infiltration of CD8+ T cells. YQ significantly increased the expression of CD4+ and CD8+ T cells in tumor and splenic tissues of tumor-bearing mice and up-regulated the expression of IL-2 and IFN-γ. Transcriptome sequencing and bioinformatics results showed that after YQ intervention, differentially expressed genes were enriched in more than one tumor-related pathway and multiple immune regulation-related biological functions. There were 12 key immune-related target genes. CONCLUSION: YQ was the key disassembled prescription of YQYYJD, exerting significant antitumor effects and immune regulation effects on NSCLC. It may have relieved T cell exhaustion and regulated the immune microenvironment to exert antitumor effects by changing lung cancer-related targets, pathways, and biological processes.

Predicting autism spectrum disorder using maternal risk factors: A multi-center machine learning study.

Autism spectrum disorder (ASD) is a neurodevelopmental disorder with a complex environmental etiology involving maternal risk factors, which have been combined with machine learning to predict ASD. However, limited studies have considered the factors throughout preconception, perinatal, and postnatal periods, and even fewer have been conducted in multi-center. In this study, five predictive models were developed using 57 maternal risk factors from a cohort across ten cities (ASD:1232, typically developing[TD]: 1090). The extreme gradient boosting model performed best, achieving an accuracy of 66.2 % on the external cohort from three cities (ASD:266, TD:353). The most important risk factors were identified as unstable emotions and lack of multivitamin supplementation using Shapley values. ASD risk scores were calculated based on predicted probabilities from the optimal model and divided into low, medium, and high-risk groups. The logistic analysis indicated that the high-risk group had a significantly increased risk of ASD compared to the low-risk group. Our study demonstrated the potential of machine learning models in predicting the risk for ASD based on maternal factors. The developed model provided insights into the maternal emotion and nutrition factors associated with ASD and highlighted the potential clinical applicability of the developed model in identifying high-risk populations.

Blocking Ubiquitin-Specific Protease 7 Induces Ferroptosis in Gastric Cancer via Targeting Stearoyl-CoA Desaturase.

Gastric cancer (GC) presents a formidable global health challenge, and conventional therapies face efficacy limitations. Ubiquitin-specific protease 7 (USP7) plays pivotal roles in GC development, immune response, and chemo-resistance, making it a promising target. Various USP7 inhibitors have shown selectivity and efficacy in preclinical studies. However, the mechanistic role of USP7 has not been fully elucidated, and currently, no USP7 inhibitors have been approved for clinical use. In this study, DHPO is identified as a potent USP7 inhibitor for GC treatment through in silico screening. DHPO demonstrates significant anti-tumor activity in vitro, inhibiting cell viability and clonogenic ability, and preventing tumor migration and invasion. In vivo studies using orthotopic gastric tumor mouse models validate DHPO's efficacy in suppressing tumor growth and metastasis without significant toxicity. Mechanistically, DHPO inhibition triggers ferroptosis, evidenced by mitochondrial alterations, lipid Reactive Oxygen Species (ROS), Malondialdehyde (MDA) accumulation, and iron overload. Further investigations unveil USP7's regulation of Stearoyl-CoA Desaturase (SCD) through deubiquitination, linking USP7 inhibition to SCD degradation and ferroptosis induction. Overall, this study identifies USP7 as a key player in ferroptosis of GC, elucidates DHPO's inhibitory mechanisms, and highlights its potential for GC treatment by inducing ferroptosis through SCD regulation.