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Objective: This study aimed to explore the relationship between climatic parameters and the daily cases of Bell's palsy (BP) among hospital outpatients, providing ecological evidence for understanding BP etiology and prevention. Methods: Retrospective analysis was conducted on data from 2187 BP patients who attended Kunshan First People's Hospital Outpatient Clinic from January 1, 2020, to December 31, 2022. Meteorological data, including temperature, relative humidity, precipitation, wind speed, sunshine duration, and atmospheric pressure, were collected and combined with daily BP case records. Additionally, air quality index was used as a covariate. Results: The number of new BP cases among outpatients showed a negative correlation with average daily temperature. A nonlinear relationship between daily average temperature and BP cases was observed through the generalized additive model (GAM). A significant negative correlation was identified between daily average temperature and BP cases, with inflection points at temperatures above 4.2°C, suggesting a potential decrease in BP risk with temperature rise beyond this threshold. Conclusion: This study provides ecological evidence of a link between climatic factors and BP occurrence. Temperature demonstrated a significant nonlinear negative correlation with daily BP incidence, highlighting temperature and cold exposure as key targets for BP prevention in Kunshan.

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Genetic interactions are adaptive within a species. Hybridization can disrupt such species-specific genetic interactions and creates novel interactions that alter the hybrid progeny overall fitness. Hybrid incompatibility, which refers to degenerative genetic interactions that decrease the overall hybrid survival and sterility, is one of the results from combining two diverged genomes in hybrids. The discovery of spontaneous lethal tumorigenesis and underlying genetic interactions in select hybrids between diverged Xiphophorus species showed that lethal pathological process can result from degenerative genetic interactions. Such genetic interactions leading to lethal phenotype are thought to shield gene flow between diverged species. However, hybrids between certain Xiphophorus species do not develop such tumors. Here we report the identification of a locus residing in the genome of one Xiphophorus species that represses an oncogene from a different species. Our finding provides insights into normal and pathological pigment cell development, regulation and a molecular mechanism in hybrid incompatibility.

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BACKGROUND: Improving hypertension control is a public health priority. However, consistent identification of uncontrolled hypertension using computable definitions in electronic health records (EHR) across health systems remains uncertain. METHODS: In this retrospective cohort study, we applied two computable definitions to the EHR data to identify patients with controlled and uncontrolled hypertension and to evaluate differences in characteristics, treatment, and clinical outcomes between these patient populations. We included adult patients (≥ 18 years) with hypertension (based on either ICD-10 codes of hypertension or two elevated blood pressure [BP] measurements) receiving ambulatory care within Yale-New Haven Health System (YNHHS; a large US health system) and OneFlorida Clinical Research Consortium (OneFlorida; a Clinical Research Network comprised of 16 health systems) between October 2015 and December 2018. We identified patients with controlled and uncontrolled hypertension based on either a single BP measurement from a randomly selected visit or all BP measurements recorded between hypertension identification and the randomly selected visit). RESULTS: Overall, 253,207 and 182,827 adults at YNHHS and OneFlorida were identified as having hypertension. Of these patients, 83.1% at YNHHS and 76.8% at OneFlorida were identified using ICD-10-CM codes, whereas 16.9% and 23.2%, respectively, were identified using elevated BP measurements (≥ 140/90 mmHg). A total of 24.1% of patients at YNHHS and 21.6% at OneFlorida had both diagnosis code for hypertension and elevated blood pressure measurements. Uncontrolled hypertension was observed among 32.5% and 43.7% of patients at YNHHS and OneFlorida, respectively. Uncontrolled hypertension was disproportionately higher among Black patients when compared with White patients (38.9% versus 31.5% in YNHHS; p < 0.001; 49.7% versus 41.2% in OneFlorida; p < 0.001). Medication prescription for hypertension management was more common in patients with uncontrolled hypertension when compared with those with controlled hypertension (overall treatment rate: 39.3% versus 37.3% in YNHHS; p = 0.04; 42.2% versus 34.8% in OneFlorida; p < 0.001). Patients with controlled and uncontrolled hypertension had similar incidence rates of deaths, CVD events, and healthcare visits at 3, 6, 12, and 24 months. The two computable definitions generated consistent results. CONCLUSIONS: While the current EHR systems are not fully optimized for disease surveillance and stratification, our findings illustrate the potential of leveraging EHR data to conduct digital population surveillance in the realm of hypertension management.

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Across the tree of life, species have repeatedly evolved similar phenotypes. While well-studied for ecological traits, there is also evidence for recurrent evolution of sexually selected traits. Swordtail fish (Xiphophorus) are a classic model system for studying sexual selection, and female Xiphophorus exhibit strong mate preferences for large male body size and a range of sexually dimorphic ornaments. Interestingly, sexually selected traits have also been lost multiple times in the genus. However, there has been uncertainty over the number of losses of ornamentation and large body size because phylogenetic relationships between species in this group have historically been controversial, partially due to prevalent gene flow. Here, we use whole-genome sequencing approaches to re-examine phylogenetic relationships within a Xiphophorus clade that varies in the presence and absence of sexually selected traits. Using wild-caught individuals, we determine the phylogenetic placement of a small, unornamented species, X. continens, confirming an additional loss of ornamentation and large body size in the clade. With these revised phylogenetic relationships, we analyze evidence for coevolution between body size and other sexually selected traits using phylogenetic comparative methods. These results provide insights into the evolutionary pressures driving the recurrent loss of suites of sexually selected traits.

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Phytoremediation of cadmium (Cd)-polluted soil by using sweet sorghum displays a tremendous potential as it is a fast-growing, high biomass and Cd tolerant energy plant. Previous study has demonstrated SbNRT1.1B expression change is in accordance with enhanced Cd accumulation by external nitrate supply in sweet sorghum. Nevertheless, underlying mechanism of SbNRT1.1B response to Cd stress is still elusive. SbNRT1.1B exhibited a positive response to Cd stress in sweet sorghum. Overexpressing SbNRT1.1B increased primary root length, shoot fresh weight, nitrate and chlorophyll concentrations compared with Col-0 under Cd stress, while complementary SbNRT1.1B rescued these decreased values in mutant chl1-5. Cd concentrations in overexpressing SbNRT1.1B, complementary SbNRT1.1B and Col-0 lines were 3.2-4.1, 2.5-3.1 and 1.2-2.1 folds of that in chl1-5. Consistent with Cd concentrations, non-protein thiol (NPT), reduced glutathione (GSH) and phytochelatins (PCs) concentrations as well as the related genes expression levels showed the same trends under Cd stress. GSH biosynthesis inhibitor failed to reverse the patterns of GSH-dependent PCs concentrations changes in different lines, suggesting that SbNRT1.1B plays an upstream role in GSH-dependent PCs biosynthesis under Cd treatment. Altogether, SbNRT1.1B enhances nitrate concentrations contributing to increased chlorophyll concentrations and GSH-dependent PCs metabolites biosynthesis, thereby improving growth and Cd concentrations in plants.

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Photoelectrochemical (PEC) organic transformation at the anode coupled with cathodic H2 generation is a potentially rewarding strategy for efficient solar energy utilization. Nevertheless, achieving the full conversion of organic substrates with exceptional product selectivity remains a formidable hurdle in the context of heterogeneous catalysis at the solid/liquid interface. Here, we put forward a quasi-homogeneous catalysis concept by using the reactive oxygen species (ROS), such as ·OH, H2O2 and SO4•-, as a charge transfer mediator instead of direct heterogeneous catalysis at the solid/liquid interface. In the context of glycerol oxidation, all ROS exhibited a preference for first-order reaction kinetics. These ROS, however, showcased distinct oxidation mechanisms, offering a range of advantages such as âˆ¼ 100 % conversion ratios and the flexibility to tune the resulting products. Glycerol oxidative formic acid with Faradaic efficiency (FE) of 81.2 % was realized by the H2O2 and ·OH, while SO4•- was preferably for glycerol conversion to C3 products like glyceraldehyde and dihydroxyacetone with a total FE of about 80 %. Strikingly, the oxidative coupling of methane to ethanol was successfully achieved in our quasi-homogeneous system, yielding a remarkable production rate of 12.27 µmol h-1 and an impressive selectivity of 92.7 %. This study is anticipated to pave the way for novel approaches in steering solar-driven organic conversions by manipulating ROS to attain desired products and conversion ratios.

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Two-dimension graphene oxide (GO) nanosheets with high and low serum protein binding profiles (high/low hard-bound protein corona/HChigh/low) are used in this study as model materials and screening tools to investigate the underlying roles of the protein corona on nanomaterial toxicities in vivo. We proposed that the in vivo biocompatibility/nanotoxicity of GO is protein corona-dependent and host immunity-dependent. The hypothesis was tested by injecting HChigh/low GO nanosheets in immunocompetent ICR/CD1 and immunodeficient NOD-scid II2rγnull mice and performed histopathological and hematological evaluation studies on days 1 and 14 post-injection. HClow GO induced more severe acute lung injury compared to HChigh GO in both immunocompetent and immunodeficient mice, with the effect being particularly pronounced in immunocompetent animals. Additionally, HClow GO caused more significant liver injury in both types of mice, with immunodeficient mice being more susceptible to its hepatotoxic effects. Moreover, administration of HClow GO resulted in increased hematological toxicity and elevated levels of serum pro-inflammatory cytokines in immunocompromised and immunocompetent mice, respectively. Correlation studies were conducted to explore the impact of distinct protein corona compositions on resulting toxicities in both immunocompetent and immunodeficient mice. This facilitated the identification of consistent patterns, aligning with those observed in vitro, thus indicating a robust in vitro-in vivo correlation. This research will advance our comprehension of how hard corona proteins interact with immune cells, leading to toxicity, and will facilitate the development of improved immune-modulating nanomaterials for therapeutic purposes.

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Metal-based chemoimmunotherapy has recently garnered significant attention for its capacity to stimulate tumor-specific immunity beyond direct cytotoxic effects. Such effects are usually caused by ICD via the activation of DAMP signals. However, metal complexes that can elicit antitumor immune responses other than ICD have not yet been described. Herein, we report that a rhodium complex (Rh-1) triggers potent antitumor immune responses by downregulating Wnt/ß-catenin signaling with subsequent activation of T lymphocyte infiltration to the tumor site. The results of mechanistic experiments suggest that ROS accumulation following Rh-1 treatment is a critical trigger of a decrease in ß-catenin and enhanced secretion of CCL4, a key mediator of T cell infiltration. Through these properties, Rh-1 exerts a synergistic effect in combination with PD-1 inhibitors against tumor growth in vivo. Taken together, our work describes a promising metal-based antitumor agent with a noncanonical mode of action to sensitize tumor tissues to ICB therapy.

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Nosema ceranae, a parasite that parasitizes and reproduces in the gut of honeybees, has become a serious threat to the global apiculture industry. RNA interference (RNAi) technology can be used to inhibit N. ceranae growth by targeting silencing the thioredoxin reductase (TrxR) in N. ceranae. However, suitable carriers are one of the reasons limiting the application of RNAi due to the easy degradation of dsRNA in honeybees. As a vesicle composed of a lipid bilayer, liposomes are a good carrier for nucleic acid delivery, but studies in honeybees are lacking. In this study, liposomes were used for double-stranded RNA (dsRNA) dsTrxR delivery triggering RNAi to inhibit the N. ceranae growth in honeybees. Compared to naked dsTrxR, liposome-dsTrxR reduced N. ceranae numbers in the midgut and partially restored midgut morphology without affecting bee survival and gut microbial composition. The results of this study confirmed that liposomes could effectively protect dsRNA from entering the honeybee gut and provide a reference for using RNAi technology to suppress honeybee pests and diseases.

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Early non-invasive diagnosis of coronary heart disease (CHD) is critical. However, it is challenging to achieve accurate CHD diagnosis via detecting breath. In this work, heterostructured complexes of black phosphorus (BP) and two-dimensional carbide and nitride (MXene) with high gas sensitivity and photo responsiveness were formulated using a self-assembly strategy. A light-activated virtual sensor array (LAVSA) based on BP/Ti3C2Tx was prepared under photomodulation and further assembled into an instant gas sensing platform (IGSP). In addition, a machine learning (ML) algorithm was introduced to help the IGSP detect and recognize the signals of breath samples to diagnose CHD. Due to the synergistic effect of BP and Ti3C2Tx as well as photo excitation, the synthesized heterostructured complexes exhibited higher performance than pristine Ti3C2Tx, with a response value 26% higher than that of pristine Ti3C2Tx. In addition, with the help of a pattern recognition algorithm, LAVSA successfully detected and identified 15 odor molecules affiliated with alcohols, ketones, aldehydes, esters, and acids. Meanwhile, with the assistance of ML, the IGSP achieved 69.2% accuracy in detecting the breath odor of 45 volunteers from healthy people and CHD patients. In conclusion, an immediate, low-cost, and accurate prototype was designed and fabricated for the noninvasive diagnosis of CHD, which provided a generalized solution for diagnosing other diseases and other more complex application scenarios.

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The uptake, translocation, and accumulation of mefentrifluconazole (MFZ), an innovative chiral triazole fungicide, in plants at the enantiomeric level are still unclear. Herein, we investigated the patterns and mechanisms of enantiomeric uptake, bioaccumulation, and translocation through several experiments. Rac-MFZ shows the strongest uptake and bioaccumulation capacity in wheat compared with its enantiomers, while S-(+)-MFZ has the highest translocation potential. Molecular docking provided evidence of the stronger translocation ability of S-(+)-MFZ than R-(-)-MFZ. Split-root experiments showed that MFZ and its enantiomers could undergo long-distance transport within the wheat. Active transport or facilitated and simple diffusion may be involved in the wheat uptake of MFZ. The limited acropetal translocation capability of MFZ may be attributed to the dominant uptake pathway of apoplastic. The concentrations of Rac-MFZ in different subcellular fractions varied greatly. In summary, this study provides novel insights for further understanding the behaviors of MFZ and its enantiomers in plants.

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Paraquat poisoning results in significant pulmonary damage, but current treatments are only minimally effective in repairing the injured lung tissues. Recent research has highlighted the promise of using stem cell therapy, namely mesenchymal stem cells, as a new method for treating paraquat toxicity. These cells have shown effectiveness in decreasing inflammation, apoptosis, and fibrosis in the mice lungs subjected to paraquat. The therapeutic implications of mesenchymal stem cells are believed to arise from their release of bioactive proteins and their capacity to regulate inflammatory responses. However, additional clinical study is required to validate these therapies' efficacy. This review thoroughly explores the pathophysiology of paraquat poisoning and the properties of mesenchymal stem cells. Additionally, it critically assesses the long-term safety and effectiveness of mesenchymal stem cell therapies, which is crucial for developing more dependable and effective treatment protocols. In summary, although mesenchymal stem cells offer promising prospects for treating lung injuries, more investigations are required to optimize their therapeutic promise and ensure their safe clinical application in the context of paraquat poisoning.

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Hypochlorous acid (HClO) serves as a critical biomarker in inflammatory diseases such as rheumatoid arthritis (RA), and its real-time imaging is essential for understanding its biological functions. In this study, we designed and synthesized a novel probe, RHMB, which ingeniously integrates rhodamine B and methylene blue fluorophores with HClO-specific responsive moieties into a single molecular framework. Upon exposure to HClO, RHMB exhibited significant dual-channel fluorescence enhancement characterized by high sensitivity (LODs of 2.55 nM and 14.08 nM), excellent selectivity, and rapid response time (within 5 s). Notably, RHMB enabled reliable imaging of both exogenous and endogenous HClO in living cells and in zebrafish, employing a unique duplex-imaging turn-on approach that highlighted its adaptability across various biological contexts. Furthermore, RHMB effectively monitored HClO fluctuations in an RA mouse model and assessed the therapeutic efficacy of diclofenac (Dic) in alleviating RA symptoms. These findings underscore the potential of RHMB as an invaluable tool for elucidating the biological roles of HClO in various diseases.

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The aim of this study was to determine whether the inclusion of 40% of common vetch (CV) hay as a feed ingredient in place of alfalfa hay (AH) would improve performance and ruminal fermentation and microbiota in fattening lambs. Twenty lambs were equally divided into two groups: control group (fed 40% AH with 20% rice straw) and CV group (fed 40% CV hay with 20% rice straw). Concerning hay quality, CV hay had greater in vitro digestibility of dry matter and neutral detergent fiber (p < 0.05) than AH. Lambs fed the CV diet had a higher average daily gain (ADG) and efficiency of feed and economy than lambs fed the control group. The NH3-N content and estimated methane produced per unit of ADG of the CV diet group were significantly lower (p < 0.05) than control group. Multiple differential microbial genera were identified, with Prevotella being the most dominant genus and a tendency towards higher (p = 0.095) in lambs offered CV diet. The higher Ruminococcus abundance (p < 0.05) was found in animals of the CV group compared to the control group. In summary, CV can be incorporated into lamb diets as a low-cost forage alternative to AH to improve feed efficiency and animal performance and to reduce methane produced per unit of ADG.

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Hybridization has been recognized to play important roles in evolution, however studies of the genetic consequence are still lagging behind in vertebrates due to the lack of appropriate experimental systems. Fish of the genus Xiphophorus are proposed to have evolved with multiple ancient and ongoing hybridization events. They have served as an informative research model in evolutionary biology and in biomedical research on human disease for more than a century. Here, we provide the complete genomic resource including annotations for all described 26 Xiphophorus species and three undescribed taxa and resolve all uncertain phylogenetic relationships. We investigate the molecular evolution of genes related to cancers such as melanoma and for the genetic control of puberty timing, focusing on genes that are predicted to be involved in pre-and postzygotic isolation and thus affect hybridization. We discovered dramatic size-variation of some gene families. These persisted despite reticulate evolution, rapid speciation and short divergence time. Finally, we clarify the hybridization history in the entire genus settling disputed hybridization history of two Southern swordtails. Our comparative genomic analyses revealed hybridization ancestries that are manifested in the mosaic fused genomes and show that hybridization often preceded speciation.

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BACKGROUND: China is the hotspot of global freshwater crab diversity, but their wild populations are facing severe pressures associated with anthropogenic factors, necessitating the need to map their taxonomic and genetic diversity and design conservation policies. RESULTS: Herein, we sequenced the mitochondrial genome of a Chinese freshwater crab species Bottapotamon fukienense, and found that it is fragmented into two chromosomes. We confirmed that fragmentation was not limited to a single specimen or population. Chromosome 1 comprised 15,111 base pairs (bp) and there were 26 genes and one pseudogene (pseudo-nad1) encoded on it. Chromosome 2 comprised 8,173 bp and there were 12 genes and two pseudogenes (pseudo-trnL2 and pseudo-rrnL) encoded on it. Combined, they comprise the largest mitogenome (23,284 bp) among the Potamidae. Bottapotamon was the only genus in the Potamidae dataset exhibiting rearrangements of protein-coding genes. Bottapotamon fukienense exhibited average rates of sequence evolution in the dataset and did not differ in selection pressures from the remaining Potamidae. CONCLUSIONS: This is the first experimentally confirmed fragmentation of a mitogenome in crustaceans. While the mitogenome of B. fukienense exhibited multiple signs of elevated mitogenomic architecture evolution rates, including the exceptionally large size, duplicated genes, pseudogenisation, rearrangements of protein-coding genes, and fragmentation, there is no evidence that this is matched by elevated sequence evolutionary rates or changes in selection pressures.

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IMPORTANCE: Hypertension poses a substantial public health challenge. Despite clinical practice guidelines for hypertension management, clinician adherence to these guidelines remains suboptimal. OBJECTIVE: To develop a taxonomy of suboptimal adherence scenarios for severe hypertension and identify barriers to guideline adherence. DESIGN, SETTING, and PARTICIPANTS: This qualitative content analysis using electronic health records (EHRs) of Yale New Haven Health System included participants who had at least 2 consecutive visits with markedly elevated blood pressure (BP; defined as at least 2 consecutive readings of systolic BP ≥160 mm Hg and diastolic BP ≥100 mm Hg) between January 1, 2013, and December 31, 2021, and no prescription for antihypertensive medication within a 90 days of the second BP measurement. Data analysis was conducted from January to December 2023. MAIN OUTCOMES AND MEASURES: The primary outcome was scenarios and influencing factors contributing to clinician nonadherence to the guidelines for hypertension management. A thematic analysis of EHR data was conducted to generate a pragmatic taxonomy of scenarios of suboptimal clinician guideline adherence in the management of severe hypertension. RESULTS: Of the 20 654 patients who met criteria, 200 were randomly selected and thematic saturation was reached after analyzing 100 patients (mean [SD] age at index visit, 66.5 [12.8] years; 50 female [50%]; 8 Black [8%]; 5 Hispanic or Latino [5%]; 85 White [85%]). Three content domains emerged: (1) clinician-related scenarios (defined as noninitiation or nonintensification of treatment due to issues relating to clinician intention, capability, or scope), which included 2 subcategories (did not address and diffusion of responsibility); (2) patient-related scenarios (defined as noninitiation or nonintensification of treatment due to patient behavioral considerations), which included 2 subcategories (patient nonadherence and patient preference); and (3) clinical complexity-related scenarios (defined as noninitiation or nonintensification of treatment due to clinical situational complexities), which included 3 subcategories (diagnostic uncertainty, maintenance of current intervention, and competing medical priorities). CONCLUSIONS AND RELEVANCE: In this qualitative study of EHR data, a taxonomy of suboptimal adherence scenarios for severe hypertension was developed and barriers to guideline adherence were identified. This pragmatic taxonomy lays the foundation for developing targeted interventions to improve clinician adherence to guidelines and patient outcomes.

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Cadmium (Cd) pollution in the soil is a serious environmental issue worldwide. Phytoextraction of Cd-polluted soil is a cost-effective, sustainable and environmentally-friendly strategy. Agricultural fertilizer management is beneficial for promoting the Cd phytoremediation efficiency. Potassium (K) is the nutrient required in the largest amount cation by plants. Sweet sorghum exhibits a substantial phytoremediation potential of Cd-polluted soil. Clarifying the mechanism of K-mediated Cd accumulation in sweet sorghum is imperative. Sweet sorghum plants were grown hydroponically with an extra K supply in the presence or absence of Cd treatment. An extra K application significantly increased plant growth under non-Cd addition, while K lost the profitable effect under Cd stress. K supplementation remarkably enhanced Cd concentrations and Cd accumulation in shoots and roots of sweet sorghum. Transcriptome analysis demonstrated that zinc ion transport, cysteine and methionine metabolism, flavonoid biosynthesis and phenylpropanoid biosynthesis pathways might contribute to the increased Cd accumulation as affected by an extra K supply. Furthermore, SbZIP9, SbSTP8, SbYS1, SbMAG and SbFOMT-like were targeted as they closely correlated with both plant growth and Cd stress in sweet sorghum. SbFOMT-like showed an independent pathway, while SbZIP9, SbSTP8, SbYS1 and SbMAG displayed positive correlations mutually. Notably, SbZIP9 and SbFOMT-like were highly expressed when compared with other target genes. Taken together, SbZIP9 and SbFOMT-like were upregulated and downregulated by an extra K supply under Cd stress, suggesting that SbZIP9 and SbFOMT-like enhances and declines Cd accumulation as regulated by K addition in sweet sorghum respectively.

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The clinical treatment of hepatocellular carcinoma (HCC) is still a heavy burden worldwide. Intracellular microRNAs (miRNAs) commonly express abnormally in cancers, thus they are potential therapeutic targets for cancer treatment. miR-21 is upregulated in HCC whereas miR-122 is enriched in normal hepatocyte but downregulated in HCC. In our study, we first generated a reporter genetic switch compromising of miR-21 and miR-122 sponges as sensor, green fluorescent protein (GFP) as reporter gene and L7Ae:K-turn as regulatory element. The reporter expression was turned up in miR-21 enriched environment while turned down in miR-122 enriched environment, indicating that the reporter switch is able to respond distinctly to different miRNA environment. Furthermore, an AAT promoter, which is hepatocyte-specific, is applied to increase the specificity to hepatocyte. A killing switch with AAT promoter and an apoptosis-inducing element, Bax, in addition to miR-21 and miR-122 significantly inhibited cell viability in Huh-7 by 70 % and in HepG2 by 60 %. By contrast, cell viability was not affected in five non-HCC cells. Thus, we provide a novel feasible strategy to improve the safety of miRNA-based therapeutic agent to cancer.