Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2.

The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key enzyme, which extensively digests CoV replicase polyproteins essential for viral replication and transcription, making it an attractive target for antiviral drug development. However, the molecular mechanism of how Mpro of SARS-CoV-2 digests replicase polyproteins, releasing the nonstructural proteins (nsps), and its substrate specificity remain largely unknown. Here, we determine the high-resolution structures of SARS-CoV-2 Mpro in its resting state, precleavage state, and postcleavage state, constituting a full cycle of substrate cleavage. The structures show the delicate conformational changes that occur during polyprotein processing. Further, we solve the structures of the SARS-CoV-2 Mpro mutant (H41A) in complex with six native cleavage substrates from replicase polyproteins, and demonstrate that SARS-CoV-2 Mpro can recognize sequences as long as 10 residues but only have special selectivity for four subsites. These structural data provide a basis to develop potent new inhibitors against SARS-CoV-2.

[Research progress on pathogenic mechanism of sepsis-induced liver injury and treatment with traditional Chinese medicine and its active components].

Sepsis is a systemic inflammatory response syndrome caused by infection, with high morbidity and mortality. Sepsis-induced liver injury(SILI) is one of the manifestations of sepsis-induced multiple organ syndrome. At present, there is no recommended pharmacological intervention for the treatment of SILI. traditional Chinese medicine(TCM), based on the holism and dialectical treatment concept, shows the therapeutic characteristics of multi-target and multi-pathway and can comprehensively prevent and treat SILI by interfering with inflammatory factors, inflammatory signaling pathways, and anti-oxidative stress and inhibiting apoptosis. This article reviewed the experimental studies on the treatment of SILI with TCM to clarify its pathogenic mechanism and therapeutic characteristics, so as to provide more ideas and directions for the development or preparation of new drugs.

ARID1A mutations in cancer development: mechanism and therapy.

AT-Rich Interaction Domain 1A (ARID1A) is an important SWItch/Sucrose Non-Fermentation (SWI/SNF) chromatin remodeling complex subunit, and its coding gene has a high mutation frequency in many cancers. Current studies have reported that ARID1A mutational status is correlated to cancer development, including cell proliferation, invasiveness, metastasis, and morphological alterations. ARID1A acts as a tumor suppressor, regulating gene transcription, participating in DNA damage response, and influencing tumor immune microenvironment and signaling pathways. The absence of ARID1A in cancer can lead to widespread dysregulation of gene expression in cancer initiation, promotion, and progression. For patients with ARID1A mutations, effective individualized treatment can improve the prognosis of patients. In this review, we aim to discuss the mechanism of ARID1A mutations in cancer development and explore the significance of discoveries for treatment.

Regulating epileptiform discharges by heterogeneous interneurons in thalamocortical model.

Inhibitory interneurons in the cortex are abundant and have diverse roles, classified as parvalbumin (PV), somatostatin (SOM), and vasoactive intestinal polypeptide (VIP) according to chemically defined categories. Currently, their involvement with seizures has been partially uncovered in physiological terms. Here, we propose a corticothalamic model containing heterogeneous interneurons to study the effects of various interneurons on absence seizure dynamics by means of optogenetic stimulation. First, the important role of feedforward inhibition caused by SRN→PV→PN projections on seizures is verified. Then, we demonstrate that light activation targeting either PV or SOM INs can control seizures. Finally, with different inhibition contributions from PV INs and SOM INs, the possible disinhibitory effect of blue light acting on VIP INs is mainly discussed. The results suggest that depending on the inhibition degree of both types, the disinhibition brought about by the VIP INs will trigger seizures, will control seizures, and will not work or cause the PNs to tend toward a high saturation state with high excitability. The circuit mechanism and the related bifurcation characteristics in various cases are emphatically revealed. In the model presented, in addition to Hopf and saddle-node bifurcations, the system may also undergo period-doubling and torus bifurcations under stimulus action, with more complex dynamics. Our work may provide a theoretical basis for understanding and further exploring the role of heterogeneous interneurons, in particular, the VIP INs, a novel target, in absence seizures.

Controllable coupling between an ultra-high-Q microtoroid cavity and a graphene monolayer for optical filtering and switching applications.

Whispering-gallery-mode optical microresonators have found impactful applications in various areas due to their remarkable properties such as ultra-high quality factor (Q-factor), small mode volume, and strong evanescent field. Among these applications, controllable tuning of the optical Q-factor is vital for on-chip optical modulation and various opto-electronic devices. Here, we report an experimental demonstration with a hybrid structure formed by an ultra-high-Q microtoroid cavity and a graphene monolayer. Thanks to the strong interaction of the evanescent wave with the graphene, the structure allows the Q-factor to be controllably varied in the range of 3.9 × 105 ∼ 6.2 × 107 by engineering optical absorption via changing the gap distance in between. At the same time, a resonant wavelength shift of 32 pm was also observed. Besides, the scheme enables us to approach the critical coupling with a coupling depth of 99.6%. As potential applications in integrated opto-electronic devices, we further use the system to realize a tunable optical filter with tunable bandwidth from 116.5 MHz to 2.2 GHz as well as an optical switch with a maximal extinction ratio of 31 dB and response time of 21 ms.

Salvianolic acid A ameliorates renal ischemia/reperfusion injury by activating Akt/mTOR/4EBP1 signaling pathway.

Salvianolic acid A (Sal A) has been shown to prevent and treat ischemic cardiovascular, as well as cerebral vascular diseases. However, little is known about Sal A in renal ischemia/reperfusion (I/R) injury. In this study, a renal I/R injury model in rats and a hypoxia/reoxygenation (H/R) model to damage proximal renal tubular cells (HK-2) were used to assess whether Sal A halts the development and progression of renal I/R injury. As compared with vehicle treatment, Sal A significantly attenuated kidney injury after renal I/R injury, accompanied by decreases in plasma creatinine, blood urea nitrogen levels, the number of apoptosis-positive tubular cells, and kidney oxidative stress. Sal A also activated phosphorylated protein kinase B (p-Akt) and phosphorylated-mammalian target of rapamycin (p-mTOR) compared with vehicle-treated I/R injury rats. In H/R-injured HK-2 cells, Sal A can reduce the levels of reactive oxygen species in a dose-related manner. Similar to the results from in vivo experiments, in vitro Sal A also increased the protein expression of phosphorylated-eukaryotic initiation factor 4E binding protein 1 (p-4EBP1) compared with vehicle. Furthermore, the cytoprotective activity of Sal A was inhibited by LY294002 and rapamycin. These findings indicate that Sal A can ameliorate renal I/R injury and promote tubular cell survival partly via the Akt/mTOR/4EBP1pathway. Sal A could be a candidate compound to prevent ischemic tissue damage.

Identification, Classification, and Functional Analysis of AP2/ERF Family Genes in the Desert Moss Bryum argenteum.

Bryum argenteum is a desert moss which shows tolerance to the desert environment and is emerging as a good plant material for identification of stress-related genes. AP2/ERF transcription factor family plays important roles in plant responses to biotic and abiotic stresses. AP2/ERF genes have been identified and extensively studied in many plants, while they are rarely studied in moss. In the present study, we identified 83 AP2/ERF genes based on the comprehensive dehydrationrehydration transcriptomic atlas of B. argenteum. BaAP2/ERF genes can be classified into five families, including 11 AP2s, 43 DREBs, 26 ERFs, 1 RAV, and 2 Soloists. RNA-seq data showed that 83 BaAP2/ERFs exhibited elevated transcript abundances during dehydration⁻rehydration process. We used RT-qPCR to validate the expression profiles of 12 representative BaAP2/ERFs and confirmed the expression trends using RNA-seq data. Eight out of 12 BaAP2/ERFs demonstrated transactivation activities. Seven BaAP2/ERFs enhanced salt and osmotic stress tolerances of yeast. This is the first study to provide detailed information on the identification, classification, and functional analysis of the AP2/ERFs in B. argenteum. This study will lay the foundation for the further functional analysis of these genes in plants, as well as provide greater insights into the molecular mechanisms of abiotic stress tolerance of B. argenteum.

A Metabolism-Based Synergy for Total Coumarin Extract of Radix Angelicae Dahuricae and Ligustrazine on Migraine Treatment in Rats.

Radix Angelicae dahuricae, containing coumarins, which might affect cytochrome P450 enzyme (CYP450) activity, has been co-administered with ligustrazine, a substrate of CYP450s, for the clinical treatment of migraine. However, whether a pharmacokinetic-based synergy exists between Radix Angelicae dahuricae and ligustrazine is still unknown. In this study, the total coumarin extract (TCE) of Radix Angelicae dahuricae (50 mg/kg, orally) reinforced the anti-migraine activity of ligustrazine by declining head scratching, plasma calcitonin gene-related peptide, and serum nitric oxide, as well as increasing plasma endothelin levels in rats (p < 0.05). Moreover, the pharmacokinetic study reflected that TCE potentiated the area under the concentration⁻time curve of ligustrazine and prolonged its mean retention time in rats (p < 0.05). Besides, the IC50 for TCE, imperatorin and isoimperatorin inhibiting ligustrazine metabolism were 5.0 ± 1.02, 1.35 ± 0.46, 4.81 ± 1.14 µg/mL in human liver microsomes, and 13.69 ± 1.11, 1.19 ± 1.09, 1.69 ± 1.17 µg/mL in rat liver microsomes, respectively. Moreover, imperatorin and isoimperatorin were CYP450s inhibitors with IC50 < 10 µM for CYP1A2, 2C9, 2D6, and 3A4. Therefore, this study concluded that Radix Angelicae dahuricae could increase ligustrazine plasma concentration and then reinforce its pharmacological effect by inhibiting its metabolism through interference with CYP450s. This could be one mechanism for the synergy between Radix Angelicae dahuricae and ligustrazine on migraine treatment.

Bioequivalence and food effect study of two zaltoprofen preparations in healthy Chinese volunteers
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OBJECTIVE: Zaltoprofen, a propionic acid derivative of nonsteroidal anti-inflammatory drug (NSAID), has powerful anti-inflammatory and analgesic effects on inflammatory pain. This study was undertaken to investigate the effect of food on the pharmacokinetic parameters of zaltoprofen capsule (trial preparation, T) and tablet (reference preparation, R), and to assess the relative bioequivalence of two zaltoprofen preparations. MATERIALS AND METHODS: In this open-label, randomized, crossover, two-state, four-period study, 24 healthy Chinese volunteers were randomized to receive a single oral dose of zaltoprofen capsule/tablet (80 mg) under fasting and fed state. Plasma samples were obtained for 24 hours and measured by a developed LC-MS/MS method. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety and tolerability were assessed throughout the study. RESULTS: 24 healthy participants received two zaltoprofen preparations. For zaltoprofen capsule and tablet, coadministration of high-fat food significantly decreased Cmax by 23 and 22%, respectively; tmax was prolonged by 0.7 hours and 0.8 hours, while the AUClast (for T, geometric mean ratio (GMR): 101.81%, 90% confidence interval (CI): 94.71 - 108.14%; for R, GMR: 101.02%, 90% CI: 93.78 - 107.12%) was not significantly affect by the food. Under fasting or fed condition, the 90% CI of T/R ratios of the geometric means for the primary pharmacokinetic parameters AUC and Cmax were within the acceptance range of 80 - 125%. CONCLUSION: These data suggest that the absorption of zaltoprofen is delayed by high-fat-food administration while total exposure is not affected. The two zaltoprofen preparations (capsule and tablet) are bioequivalent under fasting and fed state.
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Structures of SenB and SenA enzymes from Variovorax paradoxus provide insights into carbon-selenium bond formation in selenoneine biosynthesis.

Selenoneine, an ergothioneine analog, is important for antioxidation and detoxification. SenB and SenA are two crucial enzymes that form carbon-selenium bonds in the selenoneine biosynthetic pathway. To investigate their underlying catalytic mechanisms, we obtained complex structures of SenB with its substrate UDP-N-acetylglucosamine (UDP-GlcNAc) and SenA with N-α-trimethyl histidine (TMH). SenB adopts a type-B glycosyltransferase fold. Structural and functional analysis of the interaction network at the active center provide key information on substrate recognition and suggest a metal-ion-independent, inverting mechanism is utilized for SenB-mediated selenoglycoside formation. Moreover, the complex structure of SenA with TMH and enzymatic activity assays highlight vital residues that control substrate binding and specificity. Based on the conserved structure and substrate-binding pocket of the type I sulfoxide synthase EgtB in the ergothioneine biosynthetic pathway, a similar reaction mechanism was proposed for the formation of C-Se bonds by SenA. The structures provide knowledge on selenoneine synthesis and lay groundwork for further applications of this pathway.

Advancing glioblastoma treatment by targeting metabolism.

Alterations in cellular metabolism are important hallmarks of glioblastoma(GBM). Metabolic reprogramming is a critical feature as it meets the higher nutritional demand of tumor cells, including proliferation, growth, and survival. Many genes, proteins, and metabolites associated with GBM metabolism reprogramming have been found to be aberrantly expressed, which may provide potential targets for cancer treatment. Therefore, it is becoming increasingly important to explore the role of internal and external factors in metabolic regulation in order to identify more precise therapeutic targets and diagnostic markers for GBM. In this review, we define the metabolic characteristics of GBM, investigate metabolic specificities such as targetable vulnerabilities and therapeutic resistance, as well as present current efforts to target GBM metabolism to improve the standard of care.

Study on Microscopic Oil Displacement Mechanism of Alkaline-Surfactant-Polymer Ternary Flooding.

Alkali-surfactant-polymer (ASP) flooding is one of the most effective and promising ways to enhance oil recovery (EOR). The synergistic effect between alkali, surfactant, and polymer can respectively promote emulsification performance, reduce interfacial tension, and improve bulk phase viscosity, thus effectively improving flooding efficiency. However, the displacement mechanism of ASP flooding and the contribution of different components to the oil displacement effect still need further discussion. In this study, five groups of chemical slugs were injected into the fracture model after water flooding to characterize the displacement effect of weak alkali, surfactant, polymer, and their binary/ternary combinations on residual oil. Additionally, the dominant mechanism of the ASP flooding system to improve the recovery was studied. The results showed that EOR can be improved through interfacial reaction, low oil/water interfacial tension (IFT), and increased viscosity. In particular, the synergistic effect of ASP includes sweep and oil washing. As for sweep, the swept volume is expanded by the interfacial reaction between the alkali and the acidic components in Daqing crude oil, and the polymer increases the viscosity of the system. As for oil washing, the surfactant generated by the alkali cooperates with surfactants to reduce the IFT to an ultra-low level, which promotes the formation and migration of oil-in-water emulsions and increases the efficiency of oil washing. Overall, ASP can not only activate discontinuous oil ganglia in the pores within the water flooding range, but also emulsify, decompose, and migrate the continuous residual oil in the expanded range outside the water flooding. The EOR of ASP is 38.0% higher than that of water flooding. Therefore, the ASP system is a new ternary composite flooding technology with low cost, technical feasibility, and broad application prospects.

De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes.

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly all over the world. The main protease (Mpro) is significant to the replication and transcription of viruses, making it an attractive drug target against coronaviruses. Here, we introduce a series of novel inhibitors which are designed de novo through structure-based drug design approach that have great potential to inhibit SARS-CoV-2 Mproin vitro. High-resolution structures show that these inhibitors form covalent bonds with the catalytic cysteine through the novel dibromomethyl ketone (DBMK) as a reactive warhead. At the same time, the designed phenyl group beside the DBMK warhead inserts into the cleft between H41 and C145 through π-π stacking interaction, splitting the catalytic dyad and disrupting proton transfer. This unique binding model provides novel clues for the cysteine protease inhibitor development of SARS-CoV-2 as well as other pathogens.

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1.

Respiratory disease caused by coronavirus infection remains a global health crisis. Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available, their efficacy on emerging coronaviruses in the future, including SARS-CoV-2 variants, might be compromised. Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses. Cathepsin L (CTSL) and calpain-1 (CAPN1) are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response. Here, two peptidomimetic α-ketoamide compounds, 14a and 14b, were identified as potent dual target inhibitors against CTSL and CAPN1. The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of α-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1. Both showed potent and broad-spectrum anticoronaviral activities in vitro, and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern (VOCs) with EC50 values ranging from 0.80 to 161.7 nM in various cells. Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance. Moreover, 14a and 14b exhibited good oral pharmacokinetic properties in mice, rats and dogs, and favorable safety in mice. In addition, both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model. And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%. Further evaluation showed that 14a and 14b exhibited excellent anti-inflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia. Taken together, these results suggested that 14a and 14b are promising drug candidates, providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

Analysis of changes in the spatiotemporal characteristics of impervious surfaces and their influencing factors in the Central Plains Urban Agglomeration of China from 2000 to 2018.

The change of the impervious surface area (ISA) is an important feature of urban spatial expansion. Understanding the spatial and temporal change characteristics of urban impervious surfaces and their influencing factors is of great significance to the planning, management, and urbanization development of cities. This paper adopts a global artificial impervious surface dataset, with a resolution of 30 m, calculates and processes the data based on the ArcGIS platform, adopts the MK trend test method, introduces the dynamic degree, qualitatively and quantitatively analyses the changing characteristics of the ISA in the Central Plains Urban Agglomeration (CPUA), and analyzes the influencing factors of ISA changes using GeoDetector. The results show that the ISA dynamic degree was significantly enhanced from 2000 to 2018, which increased 1.86 times, indicating the accelerated outward expansion of the CPUA and the rapid level of urban development during that period. The explanatory power of the greenery coverage area on the change of the ISA in the CPUA during 2000-2018 was the strongest; the same factor has different explanatory powers for the ISA in different periods. The influencing factors have an enhanced relationship between two and two, including two-factor enhancement and nonlinear enhancement, in 2000-2009, during which the interaction level of the greenery coverage area and the GDP per capita was strong, while from 2009 to 2018, the interaction between transportation and other factors was significantly strong.

Natural arginine-based deep eutectic solvents for rapid microwave-assisted pretreatment on crystalline bamboo cellulose with boosting enzymatic conversion performance.

Development of amino acid-based natural deep eutectic solvents (DESs) pretreatment technology on lignocellulosic biomass is a promising approach to biorefinery. In this study, for arginine-based DESs with different molar ratios, the viscosity and Kamlet-Taft solvation parameters were quantified to evaluate the pretreatment performance on bamboo biomass. Further, microwave assisted DES pretreatment was eminent, evidenced by 84.8% lignin removal and increased saccharification yield (from 6.3% to 81.9%) in moso bamboo at 120 °C and ratio of 1:7 (arginine: lactic acid). Results showed degradation of lignin molecules together with release of phenolic hydroxyl units after DESs pretreatment, which is conducive to subsequent utilization. Meanwhile, DES-pretreated cellulose exhibited unique structural characteristics including destroyed crystalline region of cellulose (Crystallinity Index from 67.2% to 53.0%), decreased crystallite size (from 3.41 nm to 3.14 nm) and roughened fiber surface. Thus, arginine-based DES pretreatment has excellent potential in bamboo lignocellulose pretreatment.

Insights into key factors affecting bioconversion efficiency of rattan biomass: The supramolecular structural variations of cellulose.

Global energy concerns urged us to search for sufficient utilization of biomass to renewable energy. Herein, rattan biomass displaying herbaceous species-like anatomy and hardwood-like chemical composition was used as model of lignocellulose to determine its recalcitrance inhibiting efficient bioconversion. Delignification and continuous mild alkaline treatments were applied for deconstruction of rattan cane (Calamus simplicifolius) followed by cellulase enzymatic hydrolysis. Cellulose supramolecular structural variations were proved to be the major reason for the enhanced hydrolysis in addition to the removal of lignin and hemicelluloses matrix. Lowered crystallinity (50-65 %) as well as swelled crystallite sizes (4.8-5.0 nm) during allomorphic transformation favored the enhanced hydrolysis, rather than the crystalline cellulose II. Moreover, well-distributed separation and fibrillation of cellulose elementary fibrils also contributed to glucose yield promotion. The study will provide new insights to the strategy to efficient bioconversion of lignocellulosic biomass.

Study of gray matter atrophy pattern with subcortical ischemic vascular disease-vascular cognitive impairment no dementia based on structural magnetic resonance imaging.

Objective: This study explored the structural imaging changes in patients with subcortical ischemic vascular disease (SIVD)-vascular cognitive impairment no dementia (VCIND) and the correlation between the changes in gray matter volume and the field of cognitive impairment to provide new targets for early diagnosis and treatment. Methods: Our study included 15 patients with SIVD-normal cognitive impairment (SIVD-NCI), 63 with SIVD-VCIND, 26 with SIVD-vascular dementia (SIVD-VD), and 14 normal controls (NC). T1-weighted images of all participants were collected, and DPABI and SPM12 software were used to process the gray matter of the four groups based on voxels. Fisher's exact test, one-way ANOVA and Kruskal-Wallis H test were used to evaluate all clinical and demographic data and compare the characteristics of diencephalic gray matter atrophy in each group. Finally, the region of interest (ROI) of the SIVD-VCIND was extracted, and Pearson correlation analysis was performed between the ROI and the results of the neuropsychological scale. Results: Compared to the NC, changes in gray matter atrophy were observed in the bilateral orbitofrontal gyrus, right middle temporal gyrus, superior temporal gyrus, and precuneus in the SIVD-VCIND. Gray matter atrophy was observed in the left cerebellar region 6, cerebellar crural region 1, bilateral thalamus, right precuneus, and calcarine in the SIVD-VD. Compared with the SIVD-VCIND, gray matter atrophy changes were observed in the bilateral thalamus in the SIVD-VD (p < 0.05, family-wise error corrected). In the SIVD-VCIND, the total gray matter volume, bilateral medial orbital superior frontal gyrus, right superior temporal gyrus, middle temporal gyrus, and precuneus were positively correlated with Boston Naming Test score, whereas the total gray matter volume, right superior temporal gyrus, and middle temporal gyrus were positively correlated with overall cognition. Conclusion: Structural magnetic resonance imaging can detect extensive and subtle structural changes in the gray matter of patients with SIVD-VCIND and SIVD-VD, providing valuable evidences to explain the pathogenesis of subcortical vascular cognitive impairment and contributing to the early diagnosis of SIVD-VCIND and early warning of SIVD-VD.

Sex difference in cardiac performance in individuals with irregular shift work.

Background: sex differences existed in animal behavioral adaption and activity rhythms when exposed to chronic disruption of the circadian rhythm. Whether these differences extend to cardiac performance has not been fully investigated by cardiac imaging technology. Methods: One hundred and thirty patients enrolled in this study. Patients were divided into the day shift (DS) group and the irregular shift (IRS) group based on whether involved in the night shift and the frequency of the night shift. Comparisons of clinical data and cardiac imaging parameters were performed to identify the sex difference in cardiac function in the participants with day shift work or irregular shifts. Results: The absolute value of GLS was significantly lower in male IRS group than in male DS group. In females, no significant difference was tested in left ventricular function between the two groups. In male participants, Weekly work hours (WWH) was positively correlated with HR (r = 0.51, p = 0.02) and QTc duration (r = 0.68, p < 0.00), and weakly negatively correlated with the GLS (r = -0.38, p = 0.05). Amongst patients, there was a 2.67-fold higher relative risk (RR) for impaired GLS in males than in females, with a 95 % confidence interval (CI) of 1.20-5.61. Moreover, there was an increased risk in the male IRS group compared to the female IRS group to develop impaired GLS (RR:3.14, 95 % CI 1.20-7.84). Conclusions: The present study suggests that chronic circadian disruption brings cardiac dysfunction in people with night-shift work. Gender differences exist in the impact of circadian rhythmicity on cardiac function and may help to guide the work schedule and breaks in shift workers and bring forward prevention strategies in response to chronic circadian disruption.

Research frontiers and trends in the application of artificial intelligence to sepsis: A bibliometric analysis.

Background: With the increasing interest of academics in the application of artificial intelligence to sepsis, thousands of papers on this field had been published in the past few decades. It is difficult for researchers to understand the themes and latest research frontiers in this field from a multi-dimensional perspective. Consequently, the purpose of this study is to analyze the relevant literature in the application of artificial intelligence to sepsis through bibliometrics software, so as to better understand the development status, study the core hotspots and future development trends of this field. Methods: We collected relevant publications in the application of artificial intelligence to sepsis from the Web of Science Core Collection in 2000 to 2021. The type of publication was limited to articles and reviews, and language was limited to English. Research cooperation network, journals, cited references, keywords in this field were visually analyzed by using CiteSpace, VOSviewer, and COOC software. Results: A total of 8,481 publications in the application of artificial intelligence to sepsis between 2000 and 2021 were included, involving 8,132 articles and 349 reviews. Over the past 22 years, the annual number of publications had gradually increased exponentially. The USA was the most productive country, followed by China. Harvard University, Schuetz, Philipp, and Intensive Care Medicine were the most productive institution, author, and journal, respectively. Vincent, Jl and Critical Care Medicine were the most cited author and cited journal, respectively. Several conclusions can be drawn from the analysis of the cited references, including the following: screening and identification of sepsis biomarkers, treatment and related complications of sepsis, and precise treatment of sepsis. Moreover, there were a spike in searches relating to machine learning, antibiotic resistance and accuracy based on burst detection analysis. Conclusion: This study conducted a comprehensive and objective analysis of the publications on the application of artificial intelligence in sepsis. It can be predicted that precise treatment of sepsis through machine learning technology is still research hotspot in this field.