Maintaining calcium homeostasis as a strategy to alleviate nephrotoxicity caused by evodiamine.

Evodiamine (EVO), the main active alkaloid in Evodia rutaecarpa, was shown to exert various pharmacological activities, especially anti-tumor. Currently, it is considered a potential anti-cancer drug due to its excellent anti-tumor activity, which unfortunately has adverse reactions, such as the risk of liver and kidney injury, when Evodia rutaecarpa containing EVO is used clinically. In the present study, we aim to clarify the potential toxic target organs and toxicity mechanism of EVO, an active monomer in Evodia rutaecarpa, and to develop mitigation strategies for its toxicity mechanism. Transcriptome analysis and related experiments showed that the PI3K/Akt pathway induced by calcium overload was an important step in EVO-induced apoptosis of renal cells. Specifically, intracellular calcium ions were increased, and mitochondrial calcium ions were decreased. In addition, EVO-induced calcium overload was associated with TRPV1 receptor activation. In vivo TRPV1 antagonist and calcium chelator effects were observed to significantly reduce body weight loss and renal damage in mice due to EVO toxicity. The potential nephrotoxicity of EVO was further confirmed by an in vivo test. In conclusion, TRPV1-mediated calcium overload-induced apoptosis is one of the mechanisms contributing to the nephrotoxicity of EVO due to its toxicity, whereas maintaining body calcium homeostasis is an effective measure to reduce toxicity. These studies suggest that the clinical use of EVO-containing herbal medicines should pay due attention to the changes in renal function of patients as well as the off-target effects of the drugs.

Genome-wide association study and high-quality gene mining related to soybean protein and fat.

BACKGROUND: Soybean is one of the most important oil crops in the world, and its protein and fat are the primary sources of edible oil and vegetable protein. The effective components in soybean protein and fat have positive effects on improving human immunity, anti-tumor, and regulating blood lipids and metabolism. Therefore, increasing the contents of protein and fat in soybeans is essential for improving the quality of soybeans. RESULTS: This study selected 292 soybean lines from different regions as experimental materials, based on SLAF-seq sequencing technology, and performed genome-wide association study (GWAS) on the phenotype data from 2019-2021 Planted at the experimental base of Jilin Agricultural University, such as the contents of protein and fat of soybeans. Through the GLM model and MLM model, four SNP sites (Gm09_39012959, Gm12_35492373, Gm16_9297124, and Gm20_24678362) that were significantly related to soybean fat content were associated for three consecutive years, and two SNP sites (Gm09_39012959 and Gm20_24678362) that were significantly related to soybean protein content were associated. By the annotation and enrichment of genes within the 100 Kb region of SNP loci flanking, two genes (Glyma.09G158100 and Glyma.09G158200) related to soybean protein synthesis and one gene (Glyma.12G180200) related to lipid metabolism were selected. By the preliminary verification of expression levels of genes with qPCR, it is found that during the periods of R6 and R7 of the accumulation of soybean protein and fat, Glyma.09G158100 and Glyma.09G158200 are positive regulatory genes that promote protein synthesis and accumulation, while Glyma.12G180200 is the negative regulatory gene that inhibits fat accumulation. CONCLUSIONS: These results lay the basis for further verifying the gene function and studying the molecular mechanisms regulating the accumulation of protein and fat in soybean seeds.

Compact high-resolution spectrometer based on super-prism and local-super-collimation effects of photonic crystal.

We propose a design of the compact high-resolution photonic crystal (PhC) spectrometer with a wide working bandwidth based on both super-prism and local-super-collimation (LSC) effects. The optimizing methods, finding the ideal incident angle and oblique angle of PhC for a wider working bandwidth and ideal incident beam width and PhC size for a certain resolution requirement, are developed. Besides the theoretical work, for the first time, the experiment of such a PhC spectrometer is conducted in the microwave frequency range, and the beam-splitting effects for different frequencies in a wide working bandwidth agree very well with the theoretical predictions. According to the scalability, with the condition to control the deviations in the fabrication processes the design could be extended to optical frequency ranges, e.g., infrared, visible-light, and ultraviolet ranges. The spectrometer in optical frequencies can be implemented on silicon-on-insulator (SOI) chips as a thin-slab structure so that the operating bandwidth can be expanded further through the multi-layer design. Theoretically, the size of the ultra-high-resolution PhC spectrometer in optical frequency ranges based on our design could be two orders smaller than the traditional design.

ClpP protease modulates bacterial growth, stress response, and bacterial virulence in Brucella abortus.

The process of intracellular proteolysis through ATP-dependent proteases is a biologically conserved phenomenon. The stress responses and bacterial virulence of various pathogenic bacteria are associated with the ATP-dependent Clp protease. In this study, a Brucella abortus 2308 strain, ΔclpP, was constructed to characterize the function of ClpP peptidase. The growth of the ΔclpP mutant strain was significantly impaired in the TSB medium. The results showed that the ΔclpP mutant was sensitive to acidic pH stress, oxidative stress, high temperature, detergents, high osmotic environment, and iron deficient environment. Additionally, the deletion of clpP significantly affected Brucella virulence in macrophage and mouse infection models. Integrated transcriptomic and proteomic analyses of the ΔclpP strain showed that 1965 genes were significantly affected at the mRNA and/or protein levels. The RNA-seq analysis indicated that the ΔclpP strain exhibited distinct gene expression patterns related to energy production and conversion, cell wall/membrane/envelope biogenesis, carbohydrate transport, and metabolism. The iTRAQ analysis revealed that the differentially expressed proteins primarily participated in amino acid transport and metabolism, energy production and conversion, and secondary metabolites biosynthesis, transport and catabolism. This study provided insights into the preliminary molecular mechanism between Clp protease to bacterial growth, stress response, and bacterial virulence in Brucella strains.

[Protective effect of ophiopogonin D against isoproterenol-induced cardiomyocyte injury and targets].

This study aims to unveil the effect of ophiopogonin D(OPD) on isoproterenol(ISO)-induced apoptosis of rat cardiomyocytes and the possible targets, which is expected to provide clues for further research on the myocardial protection of ophiopogonins. Cell count kit-8(CCK-8) assay was used to detect viability of cells treated with OPD and ISO, Western blot to examine the effect of OPD and ISO on the expression of endoplasmic reticulum stress-related Bip, Bax, Perk, ATF4, caspase-12, and CHOP, flow cytometry to determine cell apoptosis rate, and Hoechst 33258 and Tunel staining to observe cell apoptosis and morphological changes. In addition, the probe for calcium ion-specific detection was employed to investigate calcium ion release from the endoplasmic reticulum, and OPD-bond epoxy-activated agarose solid-phase microspheres were prepared and used as affinity matrix to capture OPD-binding target proteins in H9 c2 cell lysate. For the target proteins of OPD identified by high-resolution mass spectrometry, the related signal pathways were enriched and the potential targets of OPD against cardiomyocyte injury were discussed. The experimental result showed that 10 µmol·L~(-1) ISO can significantly induce the expression of endoplasmic reticulum stress-related proteins and promote cell apoptosis. Different concentration of OPD can prevent the damage of myocardial cells caused by ISO. According to mass spectrometry results, 19 proteins, including Fam129 a and Pdia6, were involved in multiple signaling pathways such as the unfolded protein reaction bound by the ERN1 sensor, tricarboxylic acid cycle, and Nrf2 signal transduction pathway. The above results indicate that OPD protects cardiomyocytes by regulating multiple signaling pathways of target proteins and affecting cell cycle progression.

Deletion of the LuxR-type regulator VjbR in Brucella canis affects expression of type IV secretion system and bacterial virulence, and the mutant strain confers protection against Brucella canis challenge in mice.

Brucella spp. are facultative intracellular pathogens and zoonotic agents which pose a huge threat to human health and animal husbandry. The B. melitensis, B. abortus, and B. suis cause undulant fever and influenza-like symptoms in humans. However, the effects of B. canis have not been extensively studied. The quorum sensing-dependent transcriptional regulator VjbR influences the Brucella virulence in smooth type Brucella strains, such as B. melitensis, B. abortus and rough type Brucella ovis. However, the function of VjbR in the rough-type B. canis is unknown. In the present study, we discovered that deletion of this regulator significantly affected Brucella virulence in macrophage and mice infection models. The expression levels of virB operon and the ftcR gene were significantly altered in the vjbR mutant strain. We further investigated the protective effect of different doses of the vjbR mutant in mice and the results indicated that VjbR conferred protection against the virulent B. canis strain. This study presents the first evidence that the transcriptional regulator VjbR has important function in B. canis. In addition, according to its reduced virulence and the protective immunity it induces in mice, it can be a potential live attenuated vaccine against B. canis.

RNA-seq reveals the critical role of Lon protease in stress response and Brucella virulence.

The Brucella spp encounter stressful environment inside their host cells. The Lon protein is an important protease related to cellular protein degradation and resistance to stress in Brucella. However, the molecular mechanism between Lon protein and stress response was still unknown. In this study, it was found that the lon mutant exhibited obvious growth defect in TSB medium, compared with its parent strain. In addition, our results indicated that Lon protein was involved in resistance to various stress conditions and all the ß-lactam antibiotics tested. Although deletion of this protease did not affect Brucella virulence in macrophage, the mutant strain was significantly attenuated in mice infection model at 1 week post infection, and the expression level of several cytokine genes was significantly changed in vivo. To gain insight into the genetic basis for the distinctive phenotypic properties exhibited by the lon mutant strain, RNA-seq was performed, and the result showed that various genes involved in stress response, quorum sensing and transcriptional regulation were significantly altered in Δlon strain. Overall, these studies have preliminary uncovered the molecular mechanism between Lon protease, stress response and bacterial virulence.

Residents' perception of duty hour limits through teaching hospital accreditation status-experience in Taiwan.

Residents' work overload is a rising issue in Taiwan. Duty hours of the residents in the United States have been limited by the Accreditation Council for Graduate Medical Education Common Program Requirements since 2003; similar standards were not implemented in Taiwan until 2013. Taiwanese duty hour standards are the work hour limits adopted as part of the required teaching hospital accreditation status. In January 2015, the Ministry of Health and Welfare conducted a national survey for all house officers in Taiwan. We collected data including those on demographics and perceptions of residents regarding duty hour limits. Most respondents reported positive perceptions of the duty hour standards. They felt that these limits will improve resident education, quality of life, and patient safety. The strong incentive to follow the regulations (through teaching hospital accreditation) could help protect residents (and patients) from unsafe working conditions. However, further studies on the influence of shortened duty hour on professional development are necessary for future improvement.

[Effect of electro-acupuncture at Neiguan (PC6) and Lieque (LU7) on the expression of protein kinases in cardiomyocytes of myocardial ischemia rats].

OBJECTIVE: To study the effect of electro-acupuncture (EA) at Neiguan (PC6) and Lieque (LU7) on the expression of protein kinases in cardiomyocytes of myocardial ischemia (MI) rats. METHODS: Healthy male SD rats were randomly divided into the control group, the model group, the Neiguan point group, the Lieque point group, and the non-meridian non-acupoint group, 10 in each group by random digit table. The MI rat model was established by injecting isoprenaline hydrochloride (85 mg/kg). EA at Neiguan (PC6), Lieque (LU7), and non-meridian non-acupoint were respectively performed. Changes of the expression of protein kinases [such as protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG)] in rat cardiomyocytes were observed using Western blot. RESULTS: Compared with the control group, expression levels of PKA, PKC, and PKG increased obviously in the model group (P < 0.01). Compared with the model group, expression levels of PKA, PKC, and PKG decreased in the Neiguan point group and the Lieque point group (P < 0.01, P < 0.05). Expression levels of PKA decreased in the non-meridian non-acupoint group (P < 0.01). Compared with the Neiguan point group, expression levels of PKA, PKC, and PKG increased in the non-meridian non-acupoint group and the Lieque point group (P < 0.01, P < 0.05). Compared with the Lieque point group, expression levels of PKA, PKC, and PKG increased in the non-meridian non-acupoint group (P < 0.01, P < 0.05). CONCLUSION: EA at Neiguan (PC6) and Lieque (LU7) could decrease protein expression levels of PKA, PKC and PKG in rat myocardial cells, and the effect of acupuncture at Neiguan (PC6) was better than that obtained by EA at Lieque (LU7).

The beneficial effect of electro-acupuncture given at PC6 (Neiguan-point) by the increase in cardiac transient outward K+ current channel which depends on the gene and protein expressions in artificially induced myocardial ischemia rats.

This study explored the mechanism of electro-acupuncture (EA) at PC6 to improve the heart function by regulating the cardiac transient outward potassium current (= Ito) channel in myocardial ischemia (MI). Kv1.4 is the main component of the slow Ito (Ito.s) channel. Kv4.2 and Kv4.3 are the main components of the fast Ito (Ito.f) channel. KChIP2 is a compound protein of Ito channel. In this experiment, MI was induced by injecting isoproterenol in rats, and the gene and protein expressions of Kv1.4, Kv4.2, Kv4.3 and KChIP2 were lower [The gene and protein decreased (42.8 ± 4.3)% and (37.2 ± 4.7)% respectively.] than the control rats significantly (p < 0.05). After MI induction, the MI rats were divided into three groups, including PC6, LU7 (Lieque-point) and Non-acupoint group which were acupunctured at once a day for 7 days respectively. After EA at PC6 and LU7, the gene and protein expressions showed obvious increased [EA at PC6: the gene and protein increased (50.24 ± 5.4)% and (39.14 ± 5.3)% respectively. EA at LU7: the gene and protein increased (24.6 ± 2.8)% and (22.04 ± 5.5)% respectively] and they are all higher than MI rats significantly (p < 0.05). EA at PC6 and LU7 showed the same variation, and the effects of EA at PC6 and LU7 were better than Non-acupuncture-point (p < 0.05). The effects of EA at PC6 were significantly better [The gene and protein increased (19.74 ± 2.7)% and (14.14 ± 4.4)% respectively] than LU7 (p < 0.05). PC6 is an acupoint of the pericardium meridian, and the pericardium meridian which corresponds to adrenal gland according to Omura Y's research, can affect the heart function directly LU7 belong to the lung meridian, and the lung plays an important factor in blood circulation according to TCM. So PC6 is more effective than LU7 on heart function regulation. The results suggested that PC6 showed the target effect of meridian specificity on regulating the Kv channel in MI.

Upconverting Ultra-Thin Bi2O2CO3 Nanosheets for Synergistic Photodynamic Therapy and Radiotherapy.

Synergistic therapy has become the major therapeutic method for malignant tumors in clinical. Photodynamic therapy (PDT) and radiotherapy (RT) always combine together because of their identical anti-tumor mechanisms, that is reactive oxygen species are generated by the use of radiosensitizers after irradiation by X-ray to efficiently kill cancer cells, PDT also follows similar mechanism. Full exposure of energy-absorbing species in nanomaterials to X-ray or near-infrared light irradiation makes the energy interchange between nanomaterials and surrounding H2O or dissolved oxygen easier, however, it remains challenging. Herein, an ultrathin two-dimensional (2D) nanosheet (NS) is developed, Bi2O2CO3, doped with lanthanide ions to give out upconversion luminescence, where the high Z elements Bi, Yb, and Er promote the radio-sensitizing effect. To the surprise, lanthanide activator ions gave out completely different luminescence properties compared with traditional upconversion nanoparticles. Less dopant of Er ions in nanosheets lattice resulted in brighter red emission, which provides more efficient PDT. Under RT/PDT combined treatment, NS shows a good tumor growth-inhibiting effect. In addition, synergistic therapy requires lower radiation dose than conventional radiotherapy and lower light power than single photodynamic therapy, thus greatly reducing radiation damage caused by RT and thermal damage caused by PDT.

Positive benefit-risk ratio of Psoraleae Fructus: Comprehensive safety assessment and osteogenic effects in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Psoraleae Fructus (PF), the dried fruit of Psoralea corylifolia L., is a commonly used traditional medicine that has contributed to the treatment of orthopedic diseases for thousands of years in China. However, recent PF-related liver injury reports have drawn widespread attention regarding its potential hepatotoxicity risks. AIM OF THE STUDY: This study was aimed to evaluate the long-term efficacy and chronic toxicity of PF using a 26-week administration experiment on rats in order to simulate the clinical usage situation. MATERIALS AND METHODS: The PF aqueous extract was consecutively administrated to rats daily at dosages of 0.7, 2.0, and 5.6 g/kg (equivalent to 1-8 times the clinical doses for humans) for as long as 26 weeks. Samples were collected after 13, 26, and 32 weeks (withdrawal for 6 weeks) since the first administration. The chronic toxicity of PF was evaluated by conventional toxicological methods, and the efficacy of PF was evaluated by osteogenic effects in the natural growth process. RESULTS: In our experiments, only the H group (5.6 g/kg) for 26-week PF treatment demonstrated liver or kidney injury, which the injuries were reversible after 6 weeks of withdrawal. Notably, the PF treatment beyond 13 weeks showed significant benefits for bone growth and development in rats, with a higher benefit-risk ratio in female rats. CONCLUSIONS: PF displayed a promising benefit-risk ratio in the treatment and prevention of osteoporosis, a disease that lacks effective medicine so far. This is the first study to elucidate the benefit-risk balance associated with clinical dosage and long-term use of PF, thereby providing valuable insights for rational clinical use and risk control of PF.

The personality profile of excellent nurses in China: the 16PF.

In recent years, there has been growing interest in examining the relationship between personality characteristics and nursing service. Nurses' personality characteristics affect nursing quality and contribute toward success in the field of nursing, but little is known about excellent nurses' personality characteristics that promote the quality of nursing care. The purpose of this study was to identify excellent nurses' personality characteristics through comparison and examination of the characteristics between excellent and average nurses. A cross-sectional survey research was conducted with the 16PF. Data were collected from three hospitals in the People's Republic of China. The participants were comprised of a total of 159 excellent (N = 78) and average (N = 81) qualified nurses. Excellent nurses possess higher social boldness, openness to change, self-reliance, perfectionism, and lower dominance, vigilance, shrewdness than average nurses. The study revealed the personality profile of excellent nurses. Nurses may be selected, employed and trained according to the personality characteristics of excellent nurses. Thus nursing strategies should be developed and adjusted to get the right person in the right job the first time.

Time-course effects and mechanisms of hypobaric hypoxia on nervous system in mice.

OBJECTIVE: The aim of this study was to investigate the effect of time course on neurological impairment after acute hypobaric hypoxia exposure in mice and clarify the mechanism of acclimatization, so as to provide a suitable mice model and identify potential target against hypobaric hypoxia for further drug research. METHOD: Male C57BL/6J mice were exposed to hypobaric hypoxia at a simulated altitude of 7000 m for 1, 3, and 7 days (1HH, 3HH and 7HH respectively). The behavior of the mice was evaluated by novel object recognition (NOR) and morris water maze test (MWM), then, the pathological changes of mice brain tissues were observed by H&E and Nissl staining. In addition, RNA sequencing (RNA-Seq) was performed to characterize the transcriptome signatures, and enzyme-linked immunosorbent assay (ELISA), Real-time polymerase chain reaction (RT-PCR), and western blot (WB) were used to verify the mechanisms of neurological impairment induced by hypobaric hypoxia. RESULT: The hypobaric hypoxia condition resulted in impaired learning and memory, decreased new object cognitive index, and increased escape latency to the hidden platform in mice, with significant changes seen in the 1HH and 3HH groups. Bioinformatic analysis of RNA-seq results of hippocampal tissue showed that 739 differentially expressed genes (DEGs) appeared in the 1HH group, 452 in the 3HH group, and 183 in the 7HH group compared to the control group. There were 60 key genes overlapping in three groups which represented persistent changes and closely related biological functions and regulatory mechanisms in hypobaric hypoxia-induced brain injuries. DEGs enrichment analysis showed that hypobaric hypoxia-induced brain injuries were associated with oxidative stress, inflammatory responses, and synaptic plasticity. ELISA and WB results confirmed that these responses occurred in all hypobaric hypoxic groups while attenuated in the 7HH group. VEGF-A-Notch signaling pathway was enriched by DEGs in hypobaric hypoxia groups and was validated by RT-PCR and WB. CONCLUSION: The nervous system of mice exposed to hypobaric hypoxia exhibited stress followed by gradual habituation and thus acclimatization over time, which was reflected in the biological mechanism involving inflammation, oxidative stress, and synaptic plasticity, and accompanied by activation of the VEGF-A-Notch pathway.

Identification and Characterization of Jingmen Tick Virus in Ticks from Yunnan Imported Cattle.

Jingmen tick virus (JMTV) is a tick-borne segmented positive-sense ssRNA virus that can cause human disease. This virus has been confirmed to be widespread, having a wide host range. In human it can cause fever, headache, lymphadenopathy, and asthenia. Therefore, JMTV poses a threat to public health. In this study, we collected 478 ticks from imported cattle on three quarantine farms near the Yunnan border to detect medically significant tick-borne viruses. Our findings show that JMTV was the only detected virus, with an incidence rate of 56.67%. Phylogenetic analysis showed that our JMTV is more closely related to previously reported JMTV strains from Yunnan Province and neighboring Laos, implying that the tick-borne virus was most likely imported from Laos. In conclusion, we identified and characterized a novel JMTV strain in tick (Rhipicephalus microplus) from Yunnan imported cattle, emphasizing the importance of arbovirus quarantine of livestock imports.

The Mechanism of Houttuynia cordata Embryotoxicity Was Explored in Combination with an Experimental Model and Network Pharmacology.

Houttuynia cordata (H. cordata) is the most common herb as a food and traditional Chinese medicine. Currently, studies on its toxicity have mainly focused on hepatotoxicity. However, its potential embryotoxicity by long-term exposure is often overlooked. Objective: To investigate the effects of H. cordata on embryonic development and its toxicity mechanism by combining network pharmacology, molecular docking, and in vitro experimental methods. Methods: The effects of H. cordata on embryos were evaluated. Zebrafish embryos and embryoid bodies were administered to observe the effects of H. cordata on embryonic development. Based on network pharmacological analysis, it was found that the main active agents producing toxicity in H. cordata were oleanolic acid, lignan, and aristolactam AII. H. cordata can affect PI3K-Akt, MAPK, and Ras signaling pathways by regulating targets, such as AKT1, EGFR, CASP3, and IGF-1. RT-PCR and immunohistochemistry results showed that the expression of AKT1 and PI3K in the embryoid body was significantly reduced after drug administration (p < 0.05). Conclusions: The results of network pharmacology and in vitro experiments suggest that H. cordata may affect embryonic development by influencing the PI3K-Akt signaling pathway.

Deletion of the cheZ gene results in the loss of swimming ability and the decrease of adhesion ability to Caco-2 cells in Escherichia coli Nissle 1917.

The aim of this study was to elucidate the biological functions of the motility regulatory protein CheZ in the probiotic strain Escherichia coli Nissle 1917. A cheZ gene deletion strain Nissle 1917ΔcheZ was constructed using the CRISPR/Cas9 two-plasmid system, and the corresponding complemented strain Nissle 1917ΔcheZ/pBR322-cheZ was established. Combined studies of growth kinetics testing, motility assays, swarming motility assays, and bacterial adherence assays were performed to study the motility regulatory protein CheZ-mediated functions in the prototype Nissle 1917 strain, its isogenic cheZ mutant, and the corresponding complemented strain. The growth rate of the cheZ mutant strain was lower than that of the wild-type strain in the exponential growth phase. The motility of the cheZ mutant strain was significantly lower than that of the wild-type strain. And the adhesion ability of ΔcheZ mutant to the Caco-2 cells was significantly lower than that of the wild-type strain and complemented strain. In conclusion, the results presented in our study suggested that the deletion of the cheZ gene in E. coli Nissle 1917 led to a significant reduction of its swimming ability and a subsequent marked decrease of adhesion to the Caco-2 cells.

Projections of mortality risk attributable to short-term exposure to landscape fire smoke in China, 2021-2100: a health impact assessment study.

BACKGROUND: Landscape fire smoke, including smoke from all vegetation burning in natural and cultural landscapes, remains a threat to the health of the population. However, the future health impacts of landscape fire smoke in China have not been sufficiently investigated. We aimed to estimate the mortality risk attributable to landscape fire-related PM2·5 under different scenarios. METHODS: In this health impact assessment study, we used the projected population and landscape fire-related PM2·5 concentration to calculate deaths attributable to short-term exposure to landscape fire smoke PM2·5 during 2021-2100. We did the analysis in three defined future periods: 2021-40 (near term), 2051-70 (medium term), and 2081-2100 (long term), with 1986-2005 as the historical period. We used fire-specific short-term epidemiological functions with the regional parameters specific to China. We assessed the mortality risks of landscape fire-related smoke and further identified their spatiotemporal distribution under two shared socioeconomic pathway (SSP) scenarios: SSP1-2·6, an optimistic scenario with strict control of carbon emissions, and SSP2-4·5, an intermediate scenario with weaker control of carbon emissions. FINDINGS: The national mortality rate attributable to short-term exposure (ie, a few days) to landscape fire-related PM2·5 is projected to increase compared with historical values. The national deaths attributable to landscape fire smoke PM2·5 could peak in 2021-40, with increases of 28·10% (95% CI 14·08-53·11) under the SSP1-2·6 scenario and 37·38% (14·08-53·11) under the SSP2-4·5 scenario. Deaths would then decrease slightly during 2051-70 and 2081-2100. The provinces with the highest projected number of deaths attributable to landscape fire-related PM2·5 are located in east and south-central China, and those with the largest percentage increase in projected deaths are located in northwest and southwest China. INTERPRETATION: Our results suggest that global warming could increase the contribution of landscape fire smoke to the total PM2·5 concentration, leading to an increase in the mortality rate in China. Our findings could help policy makers implement effective interventions in hotspot areas during different periods to reduce the impact of landscape fire smoke on human health. FUNDING: The National Natural Science Foundation of China, National Key Research and Development Program of China, and the Wellcome Trust.

Integrating network pharmacology and an experimental validation strategy elucidates the protective effect and mechanism of callicarpa nudiflora against neuroinflammation.

Abnormal activation of microglia promotes neuroinflammation (NI) in Alzheimer's disease (AD). Callicarpa nudiflora Hook et Arn. (CN) is a traditional Chinese herb with a wide range of clinical applications and definite anti-inflammatory effects. However, the anti-inflammatory action and mechanism of NI are not known. The purpose of this research was to survey whether CN could inhibit lipopolysaccharide (LPS)-induced inflammatory activation in BV-2 microglia. This study used a network pharmacology and pharmacophore model-based approach to explore the molecular mechanism of CN anti-NI by combining molecular docking and experimental validation. First, we screened the key active components and targets of CN anti-NI by network pharmacology. Then, the common structural features of these functional molecules in the treatment of neuroinflammation were predicted by 3D-QSAR pharmacodynamic modeling. Finally, the molecular mechanism of the active ingredient 5-hydroxy-3,7,4'-trimethoxyflavone (THF) against neuroinflammation was validated by molecular docking and in vitro experiments. In conclusion, this study established the structure-activity relationships of the active components of CN anti-NI and provided new insights into the pharmacological mechanisms of CN anti-NI at an integrative level.

Two-Dimensional Nanosheet-Enhanced Waterborne Polyurethane Eutectogels with Ultrastrength and Superelasticity for Sensitive Strain Sensors.

Sensing materials that are ultrastrong but still superelastic and highly sensitive are crucial for meeting the requirements of future flexible sensors. However, these requirements are challenging to satisfy simultaneously due to the internal constraints among these properties. Here, an ultrastrong and superelastic eutectogel is designed and prepared using a waterborne polyurethane (WPU) network enhanced by two-dimensional (2D) nanosheets in a deep eutectic solvent. The 2D nanosheet-induced noncovalent cross-linking endows the prepared eutectogel with superelasticity and flexibility, and its elongation at break reaches 2071%, higher than those of most polymers (<1000%). Meanwhile, this eutectogel also exhibits a high tensile strength (21.6 MPa), which is strong enough to support 20 000 times its own weight. Such a composite design provides a feasible route for preparing eutectogels with outstanding comprehensive functions without trade-offs among these features. In addition, the eutectogel-assembled sensor possesses a high ionic conductivity of 0.225 S/m and a high strain sensitivity of 1.18 kPa-1. Furthermore, it can be integrated into the sensing arrays for multidimensional signal monitoring without diminishing its pristine strength and flexibility. Surprisingly, the eutectogel can be quickly disintegrated in ethanol due to the WPU's pseudoplastic behavior, providing a competitive way to dispose of waste electronic devices.