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The complex interactions were performed among non-pharmaceutical interventions, vaccinations, and hosts for all epidemics in mainland China during the spread of COVID-19. Specially, the small-scale epidemic in the city described by SVEIR model was less found in the current studies. The SVEIR model with control was established to analyze the dynamical and epidemiological features of two epidemics in Jinzhou City led by Omicron variants before and after Twenty Measures. In this study, the total population (N) of Jinzhou City was divided into five compartments: the susceptible (S), the vaccinated (V), the exposed (E), the infected (I), and the recovered (R). By surveillance data and the SVEIR model, three methods (maximum likelihood method, exponential growth rate method, next generation matrix method) were governed to estimate basic reproduction number, and the results showed that an increasing tendency of basic reproduction number from Omicron BA.5.2 to Omicron BA.2.12.1. Meanwhile, the effective reproduction number for two epidemics were investigated by surveillance data, and the results showed that Jinzhou wave 1 reached the peak on November 1 and was controlled 7 days later, and that Jinzhou wave 2 reached the peak on November 28 and was controlled 5 days later. Moreover, the impacts of non-pharmaceutical interventions (awareness delay, peak delay, control intensity) were discussed extensively, the variations of infection scales for Omicron variant and EG.5 variant were also discussed. Furthermore, the investigations on peaks and infection scales for two epidemics in dynamic zero-COVID policy were operated by the SVEIR model with control. The investigations on public medical requirements of Jinzhou City and Liaoning Province were analyzed by using SVEIR model without control, which provided a possible perspective on variant evolution in the future.

Background: The structure of age groups and social contacts of the total population influenced infection scales and hospital-bed requirements, especially influenced severe infections and deaths during the global prevalence of COVID-19. Before the end of the year 2022, Chinese government implemented the national vaccination and had built the herd immunity cross the country, and announced Twenty Measures (November 11) and Ten New Measures (December 7) for further modifications of dynamic zero-COVID polity on the Chinese mainland. With the nation-wide vaccination and modified measures background, Fuzhou COVID-19 large wave (November 19, 2022–February 9, 2023) led by Omicron BA.5.2 variant was recorded and prevailed for three months in Fujian Province. Methods: A multi-age groups susceptible-exposed-infected-hospitalized-recovered (SEIHR) COVID-19 model with social contacts was proposed in this study. The main object was to evaluate the impacts of age groups and social contacts of the total population. The idea of Least Squares method was governed to perform the data fittings of four age groups against the surveillance data from Fujian Provincial Center for Disease Control and Prevention (Fujian CDC). The next generation matrix method was used to compute basic reproduction number for the total population and for the specific age group. The tendencies of effective reproduction number of four age groups were plotted by using the Epiestim R package and the SEIHR model for in-depth discussions. The sensitivity analysis by using sensitivity index and partial rank correlation coefficients values (PRCC values) were operated to reveal the differences of age groups against the main parameters. Results: The main epidemiological features such as basic reproduction number, effective reproduction number and sensitivity analysis were extensively discussed for multi-age groups SEIHR model in this study. Firstly, by using of the next generation matrix method, basic reproduction number R0 of the total population was estimated as 1.57 using parameter values of four age groups of Fuzhou COVID-19 large wave. Given age group k, the values of R0k (age group k to age group k), the values of R0k (an infected of age group k to the total population) and the values of R^0k (an infected of the total population to age group k) were also estimated, in which the explorations of the impacts of age groups revealed that the relationship R0k>R0k>R^0k was valid. Then, the fluctuating tendencies of effective reproduction number Rt were demonstrated by using two approaches (the surveillance data and the SEIHR model) for Fuzhou COVID-19 large wave, during which high-risk group (G4 group) mainly contributed the infection scale due to high susceptibility to infection and high risks to basic diseases. Further, the sensitivity analysis using two approaches (the sensitivity index and the PRCC values) revealed that susceptibility to infection of age groups played the vital roles, while the numerical simulation showed that infection scale varied with the changes of social contacts of age groups. The results of this study claimed that the high-risk group out of the total population was concerned by the local government with the highest susceptibility to infection against COVID-19. Conclusions: This study verified that the partition structure of age groups of the total population, the susceptibility to infection of age groups, the social contacts among age groups were the important contributors of infection scale. The less social contacts and adequate hospital beds for high-risk group were profitable to control the spread of COVID-19. To avoid the emergence of medical runs against new variant in the future, the policymakers from local government were suggested to decline social contacts when hospital beds were limited.

Colias sifanica Grum-Grshimailo, 1891, is a typical montane butterfly species which occurs on the Qinghai-Tibet Plateau (QTP) and adjacent regions in China. In this study, the complete mitochondrial genome of this species was assembled from data generated by next-generation sequencing. The mitogenome was 15,151 bp in length and comprised 13 protein-coding genes (PCGs), 2 ribosomal RNA genes, 22 transfer RNA genes and a control region. The base composition of the C. sifanica mitogenome was 39.7% A, 41.3% T, 11.3% C and 7.7% G, significantly AT biased as commonly found in other Pieridae mitogenomes. Phylogenetic analyses based on all PCGs using both the maximum likelihood and Bayesian inference methods indicated that C. sifanica is closely related to C. fieldii with high support values, and the phylogenetic relationship of (Dercas + ((Gandaca + Gonepteryx) + (Phoebis + (Anteos + (Catopsilia + (Zerene + Colias))))))) was shown for the tribe Coliadini. Though both the mitogenomic gene order and overall base composition were found to be conserved, different Ka/Ks ratios for several mitogenomic PCGs were detected between Colias and other species in the tribe Coliadini.

Abstract Background Stroke is a globally dangerous disease capable of causing irreversible neuronal damage with limited therapeutic options. Meldonium, an inhibitor of carnitine-dependent metabolism, is considered an anti-ischemic drug. However, the mechanisms through which meldonium improves ischemic injury and its potential to protect neurons remain largely unknown. Methods A rat model with middle cerebral artery occlusion (MCAO) was used to investigate meldonium’s neuroprotective efficacy in vivo. Infarct volume, neurological deficit score, histopathology, neuronal apoptosis, motor function, morphological alteration and antioxidant capacity were explored via 2,3,5-Triphenyltetrazolium chloride staining, Longa scoring method, hematoxylin and eosin staining, terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling assay, rotarod test, transmission electron microscopy and Oxidative stress index related kit. A primary rat hippocampal neuron model subjected to oxygen–glucose deprivation reperfusion was used to study meldonium’s protective ability in vitro. Neuronal viability, mitochondrial membrane potential, mitochondrial morphology, respiratory function, ATP production, and its potential mechanism were assayed by MTT cell proliferation and cytotoxicity assay kit, cell-permeant MitoTracker® probes, mitochondrial stress, real-time ATP rate and western blotting. Results Meldonium markedly reduced the infarct size, improved neurological function and motor ability, and inhibited neuronal apoptosis in vivo. Meldonium enhanced the morphology, antioxidant capacity, and ATP production of mitochondria and inhibited the opening of the mitochondrial permeability transition pore in the cerebral cortex and hippocampus during cerebral ischemia–reperfusion injury (CIRI) in rats. Additionally, meldonium improved the damaged fusion process and respiratory function of neuronal mitochondria in vitro. Further investigation revealed that meldonium activated the Akt/GSK-3β signaling pathway to inhibit mitochondria-dependent neuronal apoptosis. Conclusion Our study demonstrated that meldonium shows a neuroprotective function during CIRI by preserving the mitochondrial function, thus prevented neurons from apoptosis.

Abstract The liver is the most important metabolic organ in the body. While mouse models and cell lines have further deepened our understanding of liver biology and related diseases, they are flawed in replicating key aspects of human liver tissue, particularly its complex structure and metabolic functions. The organoid model represents a major breakthrough in cell biology that revolutionized biomedical research. Organoids are in vitro three-dimensional (3D) physiological structures that recapitulate the morphological and functional characteristics of tissues in vivo, and have significant advantages over traditional cell culture methods. In this review, we discuss the generation strategies and current advances in the field focusing on their application in regenerative medicine, drug discovery and modeling diseases.

Abstract The disposal and management of waste lithium-ion batteries (LIBs) and low-density polyethylene (LDPE) plastics pose significant environmental challenges. Here we show a synergistic pyrolysis approach that employs spent lithium transition metal oxides and waste LDPE plastics in one sealed reactor to achieve the separation of Li and transition metal. Additionally, we demonstrate the preparation of nanoscale NiCo alloy@carbon nanotubes (CNTs) through co-pyrolysis of LiNi0.6Co0.2Mn0.2O2 and LDPE. The NiCo alloy@CNTs exhibits excellent catalytic activity (E onset = ~0.85 V) and the selectivity (~90%) for H2O2 production through the electrochemical reduction of oxygen. This can be attributed to the NiCo nanoalloy core and the presence of CNTs with abundant oxygen-containing functional groups (e.g., –COOH and C–O–C), as confirmed by density function theory calculations. Overall, this work presents a straightforward and green approach for valorizing and upcycling various waste LIBs and LDPE plastics.

Abstract Background Acute hypobaric hypoxia-induced brain injury has been a challenge in the health management of mountaineers; therefore, new neuroprotective agents are urgently required. Meldonium, a well-known cardioprotective drug, has been reported to have neuroprotective effects. However, the relevant mechanisms have not been elucidated. We hypothesized that meldonium may play a potentially novel role in hypobaric hypoxia cerebral injury. Methods We initially evaluated the neuroprotection efficacy of meldonium against acute hypoxia in mice and primary hippocampal neurons. The potential molecular targets of meldonium were screened using drug-target binding Huprot™ microarray chip and mass spectrometry analyses after which they were validated with surface plasmon resonance (SPR), molecular docking, and pull-down assay. The functional effects of such binding were explored through gene knockdown and overexpression. Results The study clearly shows that pretreatment with meldonium rapidly attenuates neuronal pathological damage, cerebral blood flow changes, and mitochondrial damage and its cascade response to oxidative stress injury, thereby improving survival rates in mice brain and primary hippocampal neurons, revealing the remarkable pharmacological efficacy of meldonium in acute high-altitude brain injury. On the one hand, we confirmed that meldonium directly interacts with phosphoglycerate kinase 1 (PGK1) to promote its activity, which improved glycolysis and pyruvate metabolism to promote ATP production. On the other hand, meldonium also ameliorates mitochondrial damage by PGK1 translocating to mitochondria under acute hypoxia to regulate the activity of TNF receptor-associated protein 1 (TRAP1) molecular chaperones. Conclusion These results further explain the mechanism of meldonium as an energy optimizer and provide a strategy for preventing acute hypobaric hypoxia brain injury at high altitudes.

Abstract We conducted a retrospective study to investigate risk factors for tuberculosis care-seeking delay and diagnostic delays among pediatric pulmonary tuberculosis cases in Zhejiang Province from 2013 to 2022. Among 1274 cases, 49.61% experienced tuberculosis care-seeking delays (> 14 days from symptom onset to first hospital visit) and 14.91% faced diagnostic delays (> 14 days from initial consultation to diagnosis). The proportion of care-seeking delays ranged from 37.42 to 64.89%, while diagnostic delay fluctuated from 6.11 to 21.02%. Urban residence (OR = 0.78, 95% CI 0.62–0.98, P = 0.030), first visiting a municipal-level hospital (OR = 0.57, 95% CI 0.45–0.72, P

Abstract Pyroptosis is a cell death process characterized by cell swelling until membrane rupture and release of intracellular contents. As an effective tumor treatment strategy, inducing tumor cell pyroptosis has received widespread attention. In this process, the immune components within the tumor microenvironment play a key regulatory role. By regulating and altering the functions of immune cells such as cytotoxic T lymphocytes, natural killer cells, tumor-associated macrophages, and neutrophils, tumor cell pyroptosis can be induced. This article provides a comprehensive review of the molecular mechanisms of cell pyroptosis, the impact of the tumor immune microenvironment on tumor cell pyroptosis, and its mechanisms. It aims to gain an in-depth understanding of the communication between the tumor immune microenvironment and tumor cells, and to provide theoretical support for the development of new tumor immunotherapies.

Abstract Gestational hypertension (PIH), especially pre-eclampsia (PE), is a common complication of pregnancy. This condition poses significant risks to the health of both the mother and the fetus. Emerging evidence suggests that epigenetic modifications, particularly DNA methylation, may play a role in initiating the earliest pathophysiology of PIH. This article describes the relationship between DNA methylation and placental trophoblast function, genes associated with the placental microenvironment, the placental vascular system, and maternal blood and vascular function, abnormalities of umbilical cord blood and vascular function in the onset and progression of PIH, as well as changes in DNA methylation in the progeny of PIH, in terms of maternal, fetal, and offspring. We also explore the latest research on DNA methylation-based early detection, diagnosis and potential therapeutic strategies for PIH. This will enable the field of DNA methylation research to continue to enhance our understanding of the epigenetic regulation of PIH genes and identify potential therapeutic targets.

How to capture the dynamic changes and dependencies of user behavior is a vital issue existing in point-of-interest (POI) recommendation. It mainly faces challenges including data scarcity, difficulty in extracting spatio-temporal sequence features and in capturing users?? individuated differences. In order to address these challenges, this paper proposes a time-sequence POI recommendation method based on spatio-temporal vicinity perception and implicit changes of users?? state. This method is aimed at converting the learning of user behavior into the learning of users?? latent state, combined with distance information to introduce spatial information, which effectively captures users?? mobile characteristics. Firstly, the variational autoencoder is utilized to represent the potential state of users. And then the dependency among the latent states is learnt through the graph neural network so as to capture the time-sequence dependence of user behavior. Furthermore, this paper makes use of the attention mechanism and radial basis function to capture the spatial dependence between the user and location candidate sets. Next, this paper evaluates the frequencies of user visiting each location, hence achieving point-of-interest recommendation. Experimental comparison and analysis on three real datasets demonstrate that the temporal recommendation performance of the proposed method is superior to existing benchmark algorithms.

Steel-aluminum laminates show promise in industrial manufacturing, yet their utilization is limited by unstable interface bonding. This study investigates the influence of laser texturing on the interface bonding properties of DP600/AA1060 obtained through co-extrusion. White-light interference profilometry (WLIP) and MATLAB algorithms are used to quantify different surfaces. A model is established to predict the shear load with different process angles. Furthermore, energy dispersive spectroscopy (EDS), scanning electron microscope (SEM) and X-ray diffraction (XRD) are utilized to examine the microstructure of interface fractures and DP600/AA1060 alloys. Notably, the laser texturing process (LTP) significantly enhances the interface bonding strength of the DP600/AA1060, yielding a 37% increase in maximum shear strength compared to the original sample. The prediction holds true for the process angle in the range of 0°–45° but failed between 45° and 90° due to the occurrence of tensile/compressive stress in the laser-textured area, leading to unstable bonding caused by oxides and alloy particles. However, the laser-textured surface of DP600 enhances mechanical interlocking and increases the number of micro-protrusions, thereby strengthening the interface bonding and improving the mechanical properties of co-extruded laminates.