Tailoring the Li+ Intercalation Energy of Carbon Nanocage Anodes Via Atomic Al-Doping for High-Performance Lithium-Ion Batteries.

Graphitic carbon materials are widely used in lithium-ion batteries (LIBs) due to their stability and high conductivity. However, graphite anodes have low specific capacity and degrade over time, limiting their application. To meet advanced energy storage needs, high-performance graphitic carbon materials are required. Enhancing the electrochemical performance of carbon materials can be achieved through boron and nitrogen doping and incorporating 3D structures such as carbon nanocages (CNCs). In this study, aluminum (Al) is introduced into CNC lattices via chemical vapor deposition (CVD). The hollow structure of CNCs enables fast electrolyte penetration. Density functional theory (DFT) calculations show that Al doping lowers the intercalation energy of Li+. The Al-boron (B)-nitrogen (N-doped CNC (AlBN-CNC) anode demonstrates an ultrahigh rate capacity (≈300 mAh g-1 at 10 A g-1) and a prolonged fast-charging lifespan (862.82 mAh g-1 at 5 A g-1 after 1000 cycles), surpassing the N-doped or BN-doped CNCs. Al doping improves charging kinetics and structural stability. Surprisingly, AlBN-CNCs exhibit increased capacity upon cycling due to enlarged graphitic interlayer spacing. Characterization of graphitic nanostructures confirms that Al doping effectively tailors and enhances their electrochemical properties, providing a new strategy for high-capacity, fast-charging graphitic carbon anode materials for next-generation LIBs.

Integrated analysis of bulk and single-cell RNA-seq data reveals cell differentiation-related subtypes and a scoring system in bladder cancer.

Bladder cancer (BLCA) exhibits notable molecular heterogeneity, influencing diverse clinical outcomes. However, the molecular subtypes associated with cell differentiation-related genes (CDR) and their prognostic implications remain unexplored. Analysing two GEO single-cell datasets, we identified genes linked to cell differentiation. Utilizing these genes, we explored distinct molecular subtypes. WGCNA analysis further identified CDR-associated genes, and the CDR score system, constructed using Lasso and Cox regression, was developed. Clinical prognosis and variations in immune-related factors among patient groups were assessed. Core genes were selected and confirmed through in vitro experiments. Two BLCA subtypes related to cell differentiation were identified: Subtype B demonstrated a favourable prognosis, while Subtype A exhibited significant immune cell infiltration. The CDR score system of nine genes revealed a positive correlation between higher scores and a poorer prognosis. The comprehensive analysis uncovered a positive association between CDR genes and M2 macrophages and unresponsiveness to immune therapy. Functional experiments validated that ANXA5 downregulation influences tumour cell migration without affecting proliferation. Our study reveals distinct cell differentiation-related molecular subtypes and introduces the CDR scoring system in BLCA. ANXA5 emerges as a potential therapeutic target, offering promising avenues for personalized treatment strategies.

A circular engineered sortase for interrogating histone H3 in chromatin.

Reversible modification of the histone H3 N-terminal tail is critical in regulating chromatin structure, gene expression, and cell states, while its dysregulation contributes to disease pathogenesis. Understanding the crosstalk between H3 tail modifications in nucleosomes constitutes a central challenge in epigenetics. Here we describe an engineered sortase transpeptidase, cW11, that displays highly favorable properties for introducing scarless H3 tails onto nucleosomes. This approach significantly accelerates the production of both symmetrically and asymmetrically modified nucleosomes. We demonstrate the utility of asymmetrically modified nucleosomes produced in this way in dissecting the impact of multiple modifications on eraser enzyme processing and molecular recognition by a reader protein. Moreover, we show that cW11 sortase is very effective at cutting and tagging histone H3 tails from endogenous histones, facilitating multiplex "cut-and-paste" middle down proteomics with tandem mass tags. This cut-and- paste proteomics approach permits the quantitative analysis of histone H3 modification crosstalk after treatment with different histone deacetylase inhibitors. We propose that these chemoenzymatic tail isolation and modification strategies made possible with cW11 sortase will broadly power epigenetics discovery and therapeutic development.

Isavuconazonium sulfate induces heart development defects in zebrafish larvae by upregulation of oxidative stress.

Environmental pollution remains a pressing global concern, with a substantial number of annual fatalities attributed to pollution-induced diseases. One emerging facet of environmental pollution is drug contamination, whereby pharmaceutical compounds can readily infiltrate water sources during manufacturing or utilization, subsequently being detected in various aquatic ecosystems. Some drugs have been detected in many watersheds at concentrations that can cause toxicity to aquatic organisms. Isavuconazonium sulfate (ISAV-SF), a prevalent antifungal medication, is no exception, warranting an exploration of its potential toxicity. However, limited research has been conducted in this domain. In this investigation, zebrafish were employed as a model organism to scrutinize the cardiotoxicity of ISAV-SF. Exposure of zebrafish embryos to concentrations of 0.5, 0.75, and 1 mg/L of ISAV-SF resulted in noteworthy cardiac developmental aberrations. These anomalies encompassed enlarged pericardial area, diminished heart rate, alterations in SV-BA distance, and the detachment of cardiomyocytes from the endocardium. Exposure to ISAV-SF caused disruption of the expression of genes related to cardiac development (gata4, klf2a, nkx2.5, vmhc, tbx2b), especially in the high concentration group. Moreover, the Notch signaling pathway was inhibited and oxidative stress levels were upregulated in all exposed groups. Remarkably, the administration of the antioxidant astaxanthin effectively mitigated oxidative stress levels, thus ameliorating heart developmental impairments. These results suggest that ISAV-SF may contribute to cardiac developmental defects by upregulating oxidative stress. This study serves as a pivotal reference for the utilization of ISAV-SF within the market, emphasizing the necessity to curtail its introduction into aquatic environments during production and consumption and to evaluate its repercussions on aquatic organisms.

The learning curve for modified hand-assisted retroperitoneoscopic living donor nephrectomy.

BACKGROUND: We aimed to introduce our modified hand-assisted retroperitoneoscopic living donor nephrectomy (HARPLDN) technique and define the learning curve. METHODS: One hundred thirty-eight kidney donors who underwent modified HARPLDN by the same surgeon between May 2015 and March 2022 were included. A cumulative sum (CUSUM) learning curve analysis was performed with the total operation time as the study outcome. RESULTS: In total, the mean operative time was 138.2 ± 32.1 min. The median warm ischemic time (WIT) and estimated blood loss were 90 s and 50 ml, respectively. The learning curve for the total operative time was best modeled as a second-order polynomial with the following equation: CUSUMOT (min) = (-0.09 case number2) + (12.88 case number) - 67.77 (R2 = 0.7875; p<0.05). The CUSUM learning curve included the following three unique phases: phase 1 (the initial 41 cases), representing the initial learning curve; phase 2 (the middle 43 cases), representing expert competence; and phase 3 (the final 54 cases), representing mastery. The overall 6-month graft survival rate was 99.3%, with 94.9% immediate onset of graft function without delayed graft function and 0.7% ureteral complications. CONCLUSIONS: Our modified method is safe and effective for living donor nephrectomy and has the advantages of a shorter operating time and optimized WIT. The surgeon can become familiar with the modified HARPLDN after 41 cases and effectively perform the next 97 cases.

Modified bone marrow mesenchymal stem cells derived exosomes loaded with MiRNA ameliorates non-small cell lung cancer.

The study aimed to reveal the function of LXY30 peptide-modified bone marrow mesenchymal stem cell-derived exosomes (LXY30-Exos) in NSCLC. LXY30 peptide is a peptide ligand targeting α3ß1 integrin, and LXY30 specifically binds to Exos derived from different cells. We use transmission electron microscopy to identify LXY30-Exos and tracking analysis for particles, and the LXY30-Exos internalized by NSCLC cells in vitro and targeted NSCLC tumours in vivo were verified by multiple molecular technologies. The functions of LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 were assessed using cell proliferation, migration and cell apoptosis assays. Meanwhile, the safety of the above engineered Exos was evaluated in vivo. After LXY30-Exos were isolated and identified, LXY30-Exos were confirmed to be internalized by NSCLC cells in vitro and specifically targeted NSCLC tumours in vivo. Functionally, LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 weakened the proliferation, migration and cell cycle of NSCLC cells induced cellular apoptosis in vitro and restrained the tumour progression in vivo. Meanwhile, the safety of LXY30-Exos-encapsulated miR-30c, miR-181b or miR-613 was confirmed in vivo. Overall, miR-30c, miR-181b and miR-613 encapsulated in LXY30 peptide-modified BMSC-Exos relieved NSCLC.

Investigating drug-induced urinary retention: a pharmacovigilance analysis of FDA adverse event reports from 2004 to 2024.

BACKGROUND: Drug-induced urinary retention (DIUR) can severely impact patient quality of life and complicate treatment. This study investigates the incidence and characteristics of DIUR using data from the FDA Adverse Event Reporting System (FAERS) over 20 years. METHODS: FAERS reports related to urinary retention (UR) from Q1 2004 to Q1 2024 were analyzed. Potential causative drugs were identified, and the top 30 drugs with the most UR reports were ranked. Statistical disproportionality analyses, including Proportional Reporting Ratio (PRR) and Reporting Odds Ratio (ROR), were conducted to detect significant safety signals. RESULTS: Out of 17,703,515 reports in the FAERS database 28,423 cases of UR were identified. Anticholinergics, antidepressants, and opioids were the most frequently implicated drug classes. The highest ROR and PRR values were observed for drugs like ezogabine. Additionally, less commonly associated drugs, such as adalimumab and others, were implicated, suggesting potential under-recognition of this adverse effect. However, these associations should be interpreted with caution, as they do not confirm a direct causal relationship. CONCLUSION: This study underscores the importance of pharmacovigilance in identifying and understanding DIUR. Further research is needed to confirm these findings and develop strategies to manage and reduce the risk, improving patient outcomes.

A general and rapid LC-MS/MS method for simultaneous determination of voriconazole, posaconazole, fluconazole, itraconazole and hydroxyitraconazole in IFI patients.

OBJECTIVE: To establish a rapid and universal quantitative liquid chromatography tandem mass spectrometry (LC-MS/MS) method for measuring the exposure levels of five triazole antifungal drugs in human plasma, including voriconazole, fluconazole, posaconazole, itraconazole, and hydroxyitraconazole. METHODS: A triple quadrupole mass spectrometer operating in positive ionization mode was used to detect the analyte, and multiple reaction monitoring mode was employed to gather data. The mobile phase included 0.05 % formic acid in water (phase A) and acetonitrile (phase B). The analytes were separated on an Agilent EclipsePlusC18 RRHD column (30 × 50 mm, 1.8 µm) using gradient elution. The flow rate was 0.3 mL/min with the column temperature set at 35 °C. The acetonitrile was used to pretreat the plasma sample, and the itraconazole-D5 and hydroxyitraconazole-D5 were utilized as the internal standards. RESULTS: The calibration range was from 100 to 10,000 ng/mL for posaconazole, itraconazole, and hydroxyitraconazole, from 200 to 20,000 ng/mL for fluconazole and from 50 to 5000 ng/mL for voriconazole, with linear correlation coefficients more than 0.99 for all regression curves. The intra- and inter-day accuracy and precision of the method were within ±15 %. The mean extraction recovery of all the analytes ranged from 74.32 % to 117.83 %, and the matrix effect was from 72.54 % to 111.2 %. The results of stability fell into the scope of ±15 % deviation. CONCLUSION: This newly developed method is sensitive, simple, and robust, and successfully applied in determining triazole antifungal drugs in plasma from 66 IFI patients to provide reference for safe and effective drug administration in clinical practice.

Visible-Near Infrared Independent Modulation of Hexagonal WO3 Induced by Ionic Insertion Sequence and Cavity Characteristics.

Dual-band electrochromic materials have attracted significant attention due to their ability to independently control sunlight and solar heat. However, these materials generally exhibit notable limitations, and the mechanisms for their dual-band independent regulation remain poorly understood. Here, the visible-NIR-independent regulation capabilities of hexagonal WO3 (h-WO3) are introduced for the first time. A structure-activity relationship that perfectly links the microscopic ion insertion sequence and cavity characteristics to the macroscopic dual-band electrochromic properties is established. The progressive ion intercalation process and the distinctive optical activity of the cavities are keys for enabling h-WO3 to independently modulate "bright," "cool," and "dark" modes. Notably, h-WO3 demonstrates superior dual-band electrochromic performance with a broadband full shielding effect from 550 to 2000 nm, achieving the widest full shielding band in dual-band electrochromic studies. Additionally, h-WO3 shows a high discharge capacity of 270.9 mAh m- 2 at 0.25 A m- 2, and requires only 49.1 and 209.7 mAh m- 2 to complete a full round-trip switch between "bright-cool" and "bright-dark" modes, respectively. The constructed device offers a dynamic temperature control range of up to 10.5 °C and supports a maximum voltage of 2.86 V, underscoring its considerable potential for practical applications and energy efficiency.

Risk analysis of enfortumab vedotin: A real-world approach based on the FAERS database.

Purpose: To analyze the risk of enfortumab vedotin (EV), a targeted therapy for advanced bladder cancer, using real-world data from the U.S. Food and Drug Administration's Federal Adverse Event Reporting System (FAERS). Methods: A retrospective pharmacovigilance analysis was conducted using FAERS data from Q1 2020 to Q1 2024. Adverse drug events (ADEs) related to EV were identified and categorized according to the System Organ Classes (SOCs) and specific events. Statistical methods, such as the proportional reporting ratio, reporting odds ratio (ROR), Bayesian confidence propagation neural network, and empirical Bayesian geometric mean were used to detect safety signals. Results: Of the 7,449,181 FAERS case reports, 1,617 EV-related ADEs were identified, including 101 preferred terms and 22 SOCs. The key SOCs included skin and subcutaneous tissue, metabolic, and nutritional disorders. Rare ADEs, such as lichenoid keratosis (n = 4; ROR 26.89), small intestinal perforation (n = 3; ROR 24.51), pigmentation disorder (n = 9; ROR 18.16), and cholangitis (n = 8; ROR 17.48), showed significant disproportionality. Conclusion: While most findings aligned with the existing data, new signs such as lichenoid keratosis and small intestinal perforation were identified. Further studies are necessary to validate these findings and emphasize the need for the clinical monitoring of EV-related ADEs.

Prognostic Significance and Immune Landscape of an Efferocytosis-Related Gene Signature in Bladder Cancer.

Bladder cancer poses a significant global health challenge, underscoring the imperative for precise prognostic instruments to advance patient care. Against the backdrop of efferocytosis's increasingly recognized role in cancer, this research endeavors to develop and authenticate a prognostic signature intricately linked to efferocytosis in bladder cancer. LASSO-COX regression analysis crafted an efferocytosis-related genes risk prognostic model, followed by the construction of a column chart. External validation sets confirmed the predictive accuracy of both the model and chart. Clinical, tumor microenvironment, drug sensitivity, and immunotherapy analyses were employed to comprehensively assess efferocytosis-related scores. The expression of TGFB3 key genes was validated via RT-PCR and western blotting. Further validation included Transwell, Wound healing, Colony formation, and EDU assays. We formulated and validated an efferocytosis-related genes risk model in bladder cancer, comprising 13 core genes. The risk model demonstrated autonomous prognostic significance in both univariate and multivariate Cox analyses. Following the multivariate analysis, we devised a nomogram. Moreover, by utilizing individual risk scores derived from this risk model, we successfully stratified patients into two discernible risk cohorts, unveiling noteworthy variances in immune infiltration profiles and responsiveness to immunotherapy. Notably, the model's key gene TGFB3 was validated through comprehensive experimental investigations, including Transwell assays for migration and invasion and Wound healing assays for motility on the T24 and BIU cell lines. This study has furnished innovative perspectives on an efferocytosis-related prognostic signature, elucidating the prognosis and immune milieu intricacies in patients with bladder cancer.

Deficiency of 5-HT2B receptors alleviates atherosclerosis by regulating macrophage phenotype through inhibiting interferon signalling.

BACKGROUND AND PURPOSE: Elevated levels of 5-HT have been correlated with coronary artery disease and cardiac events, suggesting 5-HT is a potential novel factor in the development of atherosclerotic cardiovascular disease. However, the underlying pathological mechanisms of the 5-HT system in atherosclerosis remain unclear. The 5-HT2B receptor (5-HT2BR), which establishes a positive feedback loop with 5-HT, has been identified as a contributor to pathophysiological processes in various vascular disorders. In this study, we investigated the immunological impact of 5-HT2BR in atherosclerosis-prone apolipoprotein E-deficient (ApoE-/-) mice. EXPERIMENTAL APPROACH: Plasma levels of 5-HT were measured in mice using an ELISA kit. Atherosclerotic plaque formation, macrophage infiltration and inflammatory signalling were assessed in ApoE-/- mice by employing both pharmacological inhibition and genetic deficiency of 5-HT2BR. Inflammasome activation was elucidated using peritoneal macrophages isolated from 5-HT2BR-deficient mice. KEY RESULTS: An upregulation of 5-HT2BR expression was observed in the aortas of ApoE-/- mice, exhibiting a strong correlation with the presence of macrophages in plaques. Atherosclerosis was attenuated in mice through pharmacological inhibition and genetic deficiency of 5-HT2BR. Additionally, a significant reduction in atherosclerotic plaque size was achieved through bone marrow reconstitution with 5-HT2BR-deficient cells. 5-HT2BR-deficient macrophages showed attenuated interferon (IFN) signalling, NLRP3 inflammasome activation, and interleukin-1ß release. Moreover, macrophages primed with 5-HT2BR deficiency displayed an anti-inflammatory phenotype. CONCLUSION AND IMPLICATIONS: These findings support the hypothesis that 5-HT2BR in macrophages plays a causal role in the development of atherosclerosis, revealing a novel perspective for potential therapeutic strategies in atherosclerosis-related diseases.

Machine Learning-based Nomograms for Predicting Clinical Stages of Initial Prostate Cancer: A Multicenter Retrospective Study.

OBJECTIVE: To construct and externally validate machine learning-based nomograms for predicting progression stages of initial prostate cancer (PCa) using biomarkers and clinicopathologic features. METHODS: Three hundred sixty-two inpatients diagnosed with PCa at the First Affiliated Hospital were randomly assigned to training and testing sets in a 3:7 ratio, while 136 PCa patients from People's Hospital formed the external validation set. Imaging and clinicopathologic information were collected. Optimal features distinguishing advanced prostate cancer (APC) and metastatic PCa (mPCa) were identified through logistic regression (LR). ML algorithms were employed to build and compare ML models. The best-performing algorithm established models for PCa progression stage. Models performance was evaluated using metrics, ROC curves, calibration, and decision curve analysis (DCA) in training, testing, and external validation sets. RESULTS: Following LR analyses, PSA (P = .001), maximum tumor diameter (P = .026), Gleason score (P <.001), and RNF41 (P <.001) were optimal features for predicting APC, while ALP (P <.001), PSA (P <.001), and GS score (P = .024) were for mPCa. Among ML models, the LR models exhibited superior performance. Consequently, the LR algorithm was used for the APC-risk-nomogram and mPCa-risk-nomogram construction, with AUC values of 0.848, 0.814, 0.810, and 0.940, 0.913, 0.910, in the training, testing, and external validation sets, respectively. Calibration and DCA curves affirmed nomograms' consistency and net benefits for clinical decision-making. CONCLUSION: In summary, ML-based APC-risk-nomogram and mPCa-risk-nomogram exhibit outstanding predictive performance for PCa progression stages. These nomograms can assist clinicians in finely categorizing newly diagnosed PCa patients, facilitating personalized treatment plans and prognosis assessment.

Preclinical Efficacy of Cap-Dependent and Independent mRNA Vaccines against Bovine Viral Diarrhea Virus-1.

Bovine viral diarrhea virus (BVDV) is an RNA virus associated with severe economic losses in animal production. Effective vaccination and viral surveillance are urgent for the prevention and control of BVDV infection. However, the application of traditional modified live vaccines and inactivated vaccines is faced with tremendous challenges. In the present study, we describe the preclinical efficacy of two BVDV mRNA vaccines tested in mice and guinea pigs, followed by a field trial in goats, where they were compared to a commercial vaccine (formaldehyde inactivated). The two mRNAs were engineered to express the envelope protein E2 of BVDV-1, the most prevalent subtype across the world, through a 5' cap-dependent or independent fashion. Better titers of neutralizing antibodies against BVDV-1 were achieved using the capped RNA in the sera of mice and guinea pigs, with maximum values reaching 9.4 and 13.7 (by -log2), respectively, on the 35th day post-vaccination. At the same time point, the antibody levels in goats were 9.1 and 10.2 for the capped and capless RNAs, respectively, and there were no significant differences compared to the commercial vaccine. The animals remained healthy throughout the experiment, as reflected by their normal leukogram profiles. Collectively, our findings demonstrate that mRNA vaccines have good safety and immunogenicity, and we laid a strong foundation for the further exploitation of efficient and safe BVDV vaccines.

DGA-grafting pyridine for ultra-selective and prior extraction of 99TcO4- from simulated spent nuclear fuel.

Selective and prior extraction of 99TcO4- ahead of uranium and plutonium separation is a beneficial strategy for the modern nuclear fuel cycle. Herein, a novel DGA-grafting pyridine ligand BisDODGA-DAPy (L1) was tailored for the efficient separation of TcO4- from simulated spent nuclear fuel based on the selectivity of pyridine and synergistic effect of diglycolamide (DGA) group. Compared to the ligands BisDOSCA-DAPy (L2) and BisDODGA-MPDA (L3) with similar structure, BisDODGA-DAPy (L1) demonstrated the better separation performance including good extraction efficiency, reusability, and high loading capacity for TcO4- under high acidic medium. The interactions of the ligands with Tc(VII)/Re(VII) have been investigated in detail using FT-IR, 1H NMR titration, UV-Vis spectrophotometric titration, ESI-HRMS and DFT simulations. The extraction mechanism affected by the protonation of ligand was elucidated under different acidity. BisDODGA-DAPy (L1) demonstrated the ultra-selective extraction ability for TcO4- from simulated spent nuclear fuel. The maximum SFTc/U and SFTc/Pu values were up to 1.29 × 104 and 5.08 × 103, respectively. In the presence of 9 × 104-fold excess of NO3-, the extraction of TcO4- was almost unaffected. Moreover, the good radiolytic stability further highlights the promising potential of this ligand for 99Tc separation. DFT calculation revealed the dominant role of DAPy and DODGA in TcO4- extraction, providing the theoretical evidence for BisDODGA-DAPy (L1) to selectively bind TcO4- over NO3-.

A novel fucoxanthin enriched seaweed gummy: Physicochemical qualities and protective effect on UVB-induced retinal müller cells.

Retinal disease has become the major cause of visual impairment and vision loss worldwide. Carotenoids, which have the potential antioxidant and eye-care activities, have been widely used in functional foods. Our previous study showed that fucoxanthin could exert photoprotective activity in UVB-induced retinal müller cells (RMCs). To extend the application of fucoxanthin in food industry, fucoxanthin, Undaria pinnatifida pulp (UPP), carrageenan, and other ingredients were mixed to prepare seaweed-flavoured photoprotective gummies in this study. The structural and functional properties of the gummies were then evaluated by physicochemical test and cell experiments. As a result, fucoxanthin enriched gummies presented favourable structural properties and flavour. The hydroxyl groups in fucoxanthin and κ-carrageenan are bonded through hydrogen bonds, forming the spatial network structure inside the gummies, enhancing its elasticity. The gummies showed significant antioxidant effect and alleviated the UVB oxidation damage in RMCs. Moreover, the main ingredients carrageenan and UPP improved the stability of fucoxanthin during in vitro digestion. The results enhance the application of fucoxanthin in functional food with photoprotective activity.

Modeling tuberculosis transmission flow in China, 2010-2012.

BACKGROUND: China has the third largest number of TB cases in the world, and the average annual floating population in China is more than 200 million, the increasing floating population across regions has a tremendous potential for spreading infectious diseases, however, the role of increasing massive floating population in tuberculosis transmission is yet unclear in China. METHODS: 29,667 tuberculosis flow data were derived from the new smear-positive pulmonary tuberculosis cases in China. Spatial variation of TB transmission was measured by geodetector q-statistic and spatial interaction model was used to model the tuberculosis flow and the regional socioeconomic factors. RESULTS: Tuberculosis transmission flow presented spatial heterogeneity. The Pearl River Delta in southern China and the Yangtze River Delta along China's east coast presented as the largest destination and concentration areas of tuberculosis inflows. Socioeconomic factors were determinants of tuberculosis flow. Some impact factors showed different spatial associations with tuberculosis transmission flow. A 10% increase in per capita GDP was associated with 10.2% in 2010 or 2.1% in 2012 decrease in tuberculosis outflows from the provinces of origin, and 1.2% in 2010 or 0.5% increase in tuberculosis inflows to the destinations and 18.9% increase in intraprovincial flow in 2012. Per capita net income of rural households and per capita disposable income of urban households were positively associated with tuberculosis flows. A 10% increase in per capita net income corresponded to 14.0% in 2010 or 3.6% in 2012 increase in outflows from the origin, 44.2% in 2010 or 12.8% increase in inflows to the destinations and 47.9% increase in intraprovincial flows in 2012. Tuberculosis incidence had positive impacts on tuberculosis flows. A 10% increase in the number of tuberculosis cases corresponded to 2.2% in 2010 or 1.1% in 2012 increase in tuberculosis inflows to the destinations, 5.2% in 2010 or 2.0% in 2012 increase in outflows from the origins, 11.5% in 2010 or 2.2% in 2012 increase in intraprovincial flows. CONCLUSIONS: Tuberculosis flows had clear spatial stratified heterogeneity and spatial autocorrelation, regional socio-economic characteristics had diverse and statistically significant effects on tuberculosis flows in the origin and destination, and income factor played an important role among the determinants.

Cisplatin resistance-related transcriptome and methylome integration identifies PCDHB4 as a novel prognostic biomarker in small cell lung cancer.

Platinum-based chemo-resistance is the major issue for the treatment of small cell lung cancer (SCLC). The integrative analysis of multi-omics data is a reliable approach for discovering novel biomarkers associated with chemo-resistance. Here, multi-omics integrative analysis and Cox regression found that higher expression of PCDHB4 was associated with poorer survival of SCLC patients who received chemotherapy. PCDHB4 gene was hypomethylated and upregulated in SCLC, which was validated in the levels of promoter methylation, mRNA, and protein expression. Mechanistically, using bulk RNA-seq data, functional enrichment analysis indicated that higher PCDHB4 expression was associated with lower immune infiltration. The analysis of single-cell RNA-seq (scRNA-seq) found that SCLC cells with PCDHB4 expression exhibited the characteristics of stemness and EMT. In addition, the high expression and hypomethylation of PCDHB4 were also significantly associated with poor survival in lung squamous cell carcinoma. In summary, PCDHB4 is a potential prognostic biomarker of platinum-based chemotherapy in SCLC.

Robotic flytrap with an ultra-sensitive 'trichome' and fast-response 'lobes'.

Nature abounds with examples of ultra-sensitive perception and agile body transformation for highly efficient predation as well as extraordinary adaptation to complex environments. Flytraps, as a representative example, could effectively detect the most minute physical stimulation of insects and respond instantly, inspiring numerous robotic designs and applications. However, current robotic flytraps face challenges in reproducing the ultra-sensitive insect-touch perception. In addition, fast and fully-covered capture of live insects with robotic flytraps remains elusive. Here we report a novel design of a robotic flytrap with an ultra-sensitive 'trichome' and bistable fast-response 'lobes'. Our results show that the 'trichome' of the proposed robotic flytrap could detect and respond to both the external stimulation of 0.45 mN and a tiny touch of a flying bee with a weight of 0.12 g. Besides, once the 'trichome' is triggered, the bistable 'lobes' could instantly close themselves in 0.2 s to form a fully-covered cage to trap the bees, and reopen to set them free after the tests. We introduce the design, modeling, optimization, and verification of the robotic flytrap, and envision broader applications of this technology in ultra-sensitive perception, fast-response grasping, and biomedical engineering studies.

Multifaceted regulation of sirtuin 2 (Sirt2) deacetylase activity.

Sirtuin 2 (Sirt2) is a member of the sirtuin family of NAD-dependent lysine deacylases and plays important roles in regulation of the cell cycle and gene expression. As a nucleocytoplasmic deacetylase, Sirt2 has been shown to target both histone and nonhistone acetylated protein substrates. The central catalytic domain of Sirt2 is flanked by flexible N and C termini, which vary in length and composition with alternative splicing. These termini are further subject to posttranslational modifications including phosphorylation. Here, we investigate the function of the N and C termini on deacetylation of nuclear substrates by Sirt2. Remarkably, we find that the C terminus autoinhibits deacetylation, while the N terminus enhances deacetylation of proteins and peptides, but not nucleosomes-a chromatin model substrate. Using protein semisynthesis, we characterize the effect of cell cycle-linked N-terminal phosphorylation at two major phosphorylation sites (Ser23/Ser25) and find that these further enhance protein/peptide deacetylation, with no effect on nucleosome deacetylation. Additionally, we find that VRK1, an established binding partner of both Sirt2 and nucleosomes, can stimulate deacetylation of nucleosomes by Sirt2, likely through an electrostatic mechanism. Taken together, these findings reveal multiple mechanisms regulating the activity of Sirt2, which allow for a broad range of activities across its multiple biological roles.