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Epithelial-mesenchymal transition (EMT) is known to be involved in airway remodeling and fibrosis of bronchial asthma. However, the molecular mechanisms leading to EMT have yet to be fully clarified. The current study was designed to reveal the potential mechanism of microRNA-21 (miR-21) and poly (ADP-ribose) polymerase-1 (PARP-1) affecting EMT through the PI3K/AKT signaling pathway. Human bronchial epithelial cells (16HBE cells) were transfected with miR-21 mimics/inhibitors and PARP-1 plasmid/small interfering RNA (siRNA). A dual luciferase reporter assay and biotin-labeled RNA pull-down experiments were conducted to verify the targeting relationship between miR-21 mimics and PARP-1. The migration ability of 16HBE cells was evaluated by Transwell assay. Quantitative real-time polymerase chain reaction and Western blotting experiments were applied to determine the expression of Snail, ZEB1, E-cadherin, N-cadherin, Vimentin, and PARP-1. The effects of the PI3K inhibitor LY294002 on the migration of 16HBE cells and EMT were investigated. Overexpression of miR-21 mimics induced migration and EMT of 16HBE cells, which was significantly inhibited by overexpression of PARP-1. Our findings showed that PARP-1 was a direct target of miR-21, and that miR-21 targeted PARP-1 to promote migration and EMT of 16HBE cells through the PI3K/AKT signaling pathway. Using LY294002 to block PI3K/AKT signaling pathway resulted in a significant reduction in the migration and EMT of 16HBE cells. These results suggest that miR-21 promotes EMT and migration of HBE cells by targeting PARP-1. Additionally, the PI3K/AKT signaling pathway might be involved in this mechanism, which could indicate its usefulness as a therapeutic target for asthma.

The tumor microenvironment is proposed to contribute substantially to the progression of cancers, including breast cancer. Cancer-associated fibroblasts (CAFs) are the most abundant components of the tumor microenvironment. Studies have revealed that CAFs in breast cancer originate from several types of cells and promote breast cancer malignancy by secreting factors, generating exosomes, releasing nutrients, reshaping the extracellular matrix, and suppressing the function of immune cells. CAFs are also becoming therapeutic targets for breast cancer due to their specific distribution in tumors and their unique biomarkers. Agents interrupting the effect of CAFs on surrounding cells have been developed and applied in clinical trials. Here, we reviewed studies examining the heterogeneity of CAFs in breast cancer and expression patterns of CAF markers in different subtypes of breast cancer. We hope that summarizing CAF-related studies from a historical perspective will help to accelerate the development of CAF-targeted therapeutic strategies for breast cancer.

Esophageal squamous cell carcinoma (ESCC) is a common malignancy worldwide and often diagnosed at advanced stages with poor prognosis. Combination of radiotherapy and immunotherapy seems to be a promising approach for treating ESCC. This comprehensive review article summarizes the current state of combination of radiotherapy and immunotherapy in locally advanced/metastatic ESCC, delineates the clinical trials that merit attention, and outlines unresolved issues and future research directions in this field. The clinical trial findings suggest that radio-immunotherapy combination may improve tumor response and overall survival with manageable side effects, highlighting the importance of patient selection and the necessity for further research to optimize treatment strategies. Issues such as irradiation dosage, fractionation regimen, irradiation site and technique of radiotherapy, as well as the timing, sequence and duration of combination therapy will all affect treatment outcomes, justifying further in-depth investigation.

Leaching is the continuous separation of elements from the mineral surface which is composed of coordination polyhedrons of atoms. The interaction between surface elements and the leaching agent is the prerequisite for separation. Density functional theory calculations are used to reveal the interaction between leaching agent ions (H+), activator agent ions (Mn4+), and the vanadium-containing biotite surface. According to the calculation results, the oxidative activation acid-leaching process is simulated. In the oxidative activation acid-leaching process, the surface oxygen atoms first absorb hydrogen ions to complete the hydroxylation process and then combines hydrogen ions again to form water molecules. And when the surface tetrahedron has oxygen defects, the oxidant ions can further corrode the tetrahedral structure with oxygen defects. This corrosion can destroy tetrahedral structures. When the tetrahedral structure is destroyed, cations are released from the mineral surface into the solution. In this study, the corrosion behavior of the oxidant ion and its effect on the leaching rate is found. The separation of atoms from the surface under oxidative activation leaching environments is simulated at the atomic level, and the mechanism of the activated leaching process is revealed by electron probe, scanning electron microscopy, infrared, and other methods.

Microalgae show great potential for nutrient removal from piggery digestate. However, full-strength piggery digestate have been found to severely inhibit microalgal growth. In this study, microalgae were coupled into the electric field (EF)system to form an electric field-microalgae system (EFMS). The effects of EF characteristics and environmental conditions on the growth of

With the crystal structure prediction package AISP, thgraphene composed of tetragonal and heptagonal carbon rings is theoretically predicted as a bifunctional HER/OER electrocatalyst and potassium-ion anode material.

The thermal-driven current through the device is dominated by the spin-down electrons within a wide temperature range.

Sharing among different pathogens and commensals inhabiting same hosts and environments has significant implications for antimicrobial resistance (AMR), especially in settings with high antimicrobial exposure. We analysed 661E. coliandS. entericaisolates collected within and across hosts and environments, in 10 Chinese chicken farms over 2.5 years using novel data-mining methods. Most isolates within same hosts possessed same clinically relevant AMR-carrying mobile genetic elements (plasmids: 70.6%, transposons: 78%), which also showed recent common evolution. Machine learning revealed known and novel AMR-associated mutations and genes underlying resistance to 28 antimicrobials and primarily associated with resistance inEscherichia coliand susceptibility inSalmonella enterica. Many of these genes were essential and affected same metabolic processes in both species, albeit with varying degrees of phylogenetic penetration. Multi-modal strategies are crucial to investigate the interplay of mobilome, resistance and metabolism in cohabiting bacteria, especially in ecological settings where community-driven resistance selection occurs.

The use of antimicrobials in livestock production is associated with the rise of antimicrobial resistance (AMR). China is the largest consumer of antimicrobials and improving AMR surveillance methods may help inform intervention. Here, we report the surveillance of ten large-scale chicken farms and four connected abattoirs from three Chinese provinces, over 2.5 years. By using a bespoke data-mining approach based on machine learning, we analysed microbiomes and resistomes from birds, carcasses and environments. We found that a core subset of the chicken gut resistome and microbiome, featuring clinically relevant bacteria and antibiotic resistance genes correlates with AMR profiles of Escherichia coli colonizing the gut. This core is itself influenced by environmental temperature and humidity, contains clinically relevant mobile ARGs shared by chickens and environments, and correlates with antimicrobial usage. Our findings indicate a viable route to optimize AMR surveillance in livestock production.

The spatial dimension of the journey-to-work has important implications for land use and development policymaking and has been widely studied. One thrust of this research is concerned with the disaggregation of workers into subgroups for understanding disparities in commute. Most of these studies, however, were limited to the disaggregation by single socioeconomic class. Hence, this research aims to examine commuting disparities across commuter subgroups stratified by two socioeconomic variables—income and race—using a visual analytics approach. By applying the doubly constrained spatial interaction model to the 2014 Longitudinal Employer-Household Dynamics data, this research first synthesizes commuting flows for Downtown Houston workers across income-race subgroups at the tract level in Harris County, Texas, USA. It then uses bivariate choropleth mapping to visualize the spatial distributions of major Downtown Houston commuter neighborhoods by income-race classes, and significant commuting disparities are identified across income-race subgroups. The results highlight the importance of considering income and race simultaneously for commuting research. The visualization could help policymakers clearly identify the unequal commute across worker subgroups and inform policymaking.

The genus Piper, a member of the Piperaceae family, comprises2000 species, of which many are well known to possess considerable economic and medicinal values. Lignans are essential ingredients and are rich in Piper plants. Although many phytochemical studies have reported many lignans identified from Piper plants, comprehensive research has not reviewed these compounds. Hence, the present review reports on natural lignans from the genus Piper and their pharmacological activities. At least 275 lignans have been discovered from the Piper genus until October 2022, including traditional lignans, neolignans, oxyneolignans, norlignans, secolignans, and polyneolignans, especially some neolignans and norlignans with novel and complex scaffolds. In addition, these lignans have been reported to show various pharmacological activities, such as antimicrobial, anti-inflammatory, neuroprotective, antioxidative, anti-platelet aggregation, cytotoxic, antiparasitic, CYP3A4 inhibitory activities, and so on. The current work presents an up-to-date critical review and a systematic summary of publications on lignans from the genus Piper to lay the groundwork and show better insights for further investigations.

To investigate the mechanism underlying the regulatory effect of melatonin on chronic sleep deprivation-related cognitive impairment.Chronic sleep deprivation (CSD) model was established using the MMPM method. After the model was established, melatonin receptor agonist and inhibitor were given, respectively. Water maze was conducted to record the escape latency and the duration of crossing the platform of space exploration. The concentration of TNF-α, IL-6, MDA, and SOD was measured by ELISA. Immunofluorescence was used to determine the expression level of CD86 and CD206, while the mRNA expression of Bax, Bcl-2, P65, IκB, and BMAL1 was detected by qPCR. Western blotting assay was utilized to determine the protein expression of Bax, Bcl-2, P65, p-P65, IκB, p-I κB, and BMAL1.Compared with the control, the escape latency was greatly increased on the second and third day, accompanied by the increased expression of TNF-α, IL-6, MDA, and SOD in serum. Furthermore, dramatically upregulated Bax, Bcl-2, P65, IκB, and CD86 were observed in the model group, accompanied by the declined expression level of BMAL1 and CD206. Compared with the model group, the escape latency was declined, the concentration of TNF-α, IL-6, MDA, and SOD was decreased, the expression level of Bax, Bcl-2, P65, IκB, and CD86 was declined, and the level of BMAL1 and CD206 was promoted by the treatment of the melatonin agonist, while the opposite results were observed under the treatment of the melatonin inhibitor.Melatonin upregulates BMAL1 to attenuate chronic sleep deprivation-related cognitive impairment by alleviating oxidative stress.

Salmonella enterica serotype Indiana (S. Indiana) in Chinese poultry meat has aroused widespread concern because of its high prevalence and strong antimicrobial resistance. In consideration of the relationship in our previous study between S. Indiana and co-resistance to ciprofloxacin and cefotaxime (CIP-CTX), which were the first-line drug which were used in Salmonella infection in clinical, the antimicrobial resistance (AMR) of 224 CIP-CTX co-resistant S. Indiana isolated from retail chicken samples in China were investigated, with the aim of characterizing the AMR profiles and related resistance mechanisms to ciprofloxacin and cefotaxime among these CIP-CTX co-resistant S. Indiana isolates, all of which showed multi-drug-resistant (MDR) phenotypes. GyrA (S83F and D87N/G) with ParC (T57S and S80R) were the dominant amino acid substitution types, with oqxA, oqxB, and aac (6′)-Ib-cr identified as common plasmid-mediated quinolone resistance (PMQR)-encoding genes. Five blaCTX-M gene subtypes were identified with blaCTX-M-65 ranking at the top. Equally important, we obtained one isolate CFSA664 harboring the mcr-1 gene was ESBL producer with co-resistance to nine in ten classes of tested drugs inclduing colistin. A single circular chromosome and 3 circular plasmids were found in its genome. Among the 26 AMR genes identified, 24 were located on plasmid pCFSA664-1, including three ESBL genes, while plasmid pCFSA664-3 owning only the mcr-1 gene and sharing the same backbone structure with plasmids from Enterobacteriaceae. No insertion sequences were found near the mcr-1 gene but a relaxase-encoding gene in the flank, which could transfer into E. coli J53 at a relatively high frequency. S. Indiana in this study exhibited highly drug-resistant phenotypes, contributing to the acceleration of the dissemination and emergence of this pathogen among different sources. Surveillance and a One Health strategy are needed to limit the emergence of S. Indiana along the food chain.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine via nitroglycerin (NTG) injection. The in vivo experiments demonstrated that XZR attenuated allodynia and photophobia in rats with NTG-induced migraine, and XZR also demonstrated analgesic effects. XZR reversed the abnormal levels of nitric oxide, 5-hydroxytryptamine (5-HT), calcitonin gene-related peptide (CGRP), and substance P (SP) to normal levels. XZR also downregulated inflammatory reactions, including mast cell degranulation and serum IL-1β, IL-6, and TNF-α levels. In terms of mechanism, we revealed that XZR treated NTG-induced migraine through the inhibition of neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) expression in both the trigeminal nucleus caudalis (TNC) and periaqueductal gray matter (PAG), as well as the total NOS enzyme activity, which regulated the NF-κB signaling pathway. Additionally, imperatorin and xanthotoxin, two major ingredients of XZR, showed a high binding affinity to nNOS (Gly468-Leu616). In vitro, XZR, imperatorin, and xanthotoxin inhibited the nNOS expression and the NF-κB signaling pathway in lipopolysaccharide (LPS)-stimulated PC12 cells. In conclusion, we demonstrated the therapeutic effects of XZR and provided evidence that XZR played a critical anti-inflammatory role by suppressing NOS and NF-κB signaling pathway activation. Imperatorin and xanthotoxin were potential bioactive components of XZR. The findings from this study supported that XZR was a candidate herbal drug for migraine therapy.

Epimedii Folium is widely used worldwide as an herbal supplement, and the risk of its induced liver damage has emerged in recent years. Our preliminary study has found that, among several Epimedii Folium species specified in the Chinese Pharmacopoeia, Epimedium koreanum Nakai has a more severe propensity for hepatotoxicity. However, the mechanism of hepatotoxicity of Epimedium koreanum Nakai is still unclear. In this study, untargeted metabolomics was performed to analyze the serum and liver tissue to explore the mechanism of hepatotoxicity of Epimedium koreanum Nakai. The results of experiments in vivo showed that, after 28 days of exposure to Epimedium koreanum Nakai ethanol extract (EEE), the liver weight, levels of AST, ALP, TBIL, etc. in serum of rats in the EEE group were significantly increased, as well as severe cytoplasmic vacuolation appeared in the liver tissue, which suggested that EEE has significant hepatotoxicity. Subsequently, the results of metabolomics revealed significant changes in the metabolic profile in the liver and serum of rats after EEE exposure, in which metabolites in serum such as flavin mononucleotide, phenylacetylglycine, glutathione, l-tryptophan, and sphingomyelin were able to accurately identify liver injury caused by EEE and could be used as serum markers to reflect EEE-induced liver injury. The KEGG pathway enrichment analysis revealed that EEE caused extensive effects on rats' metabolic pathways. Some of the most affected pathways included glutathione metabolism, glutamate metabolism pathway, primary bile acid biosynthesis pathway, and sphingolipid metabolism pathway, which were all directed to the biological process of ferroptosis. Then, the main markers related to ferroptosis in the liver were examined, and the results demonstrated that the content of malondialdehyde was significantly increased, the activity of superoxide dismutase was significantly reduced, the ferroptosis inhibitory proteins GPX4 and System xc− were significantly downregulated, and the ferroptosis-promoting protein ACSL4 was significantly up-regulated. Judging from these results, we concluded that the mechanism of hepatotoxicity of Epimedium koreanum Nakai was probably related to the induction of ferroptosis in hepatocytes.

A total of 620 samples collected from two factories in China producing powdered infant formula (PIF) between July and November 2016 were analyzed for Cronobacter. Antimicrobial susceptibility, pulsed-field gel electropho-resis (PFGE), and biofilm formation of Cronobacter were carried out. The results showed that 2.26% samples were positive for Cronobacter among the 33 isolates that were identified. All Cronobacter isolates were susceptible to 12 antimicrobial agents tested except one isolate which showed intermediate resistance to Chloramphenicol. PFGE analysis showed that nine clusters comprising the 33 isolates were identified, among which C8, C4, and C5 were the predominant types. All 33 isolates were capable of forming biofilm, and particularly, C. malonaticus isolates showed a good biofilm-forming ability at both 28°C and 37°C. The results illustrated that it is necessary for PIF manufactures to develop control measures for reducing Cronobacter contamination and its associated foodborne illness among infants.

International audience; Klebsiella pneumoniae is considered an opportunistic pathogen, constituting an ongoing health concern for immunocompromised patients, the elderly, and neonates. Reports on the isolation of K. pneumoniae from other sources are increasing, many of which express multidrug-resistant (MDR) phenotypes. Three phylogroups were identified based on nucleotide differences. Niche environments, including plants, animals, and humans appear to be colonized by different phylogroups, among which KpI (K. pneumoniae) is commonly associated with human infection. Infections with K. pneumoniae can be transmitted through contaminated food or water and can be associated with community-acquired infections or between persons and animals involved in hospital-acquired infections. Increasing reports are describing detections along the food chain, suggesting the possibility exists that this could be a hitherto unexplored reservoir for this opportunistic bacterial pathogen. Expression of MDR phenotypes elaborated by these bacteria is due to the nature of various plasmids carrying antimicrobial resistance (AMR)-encoding genes, and is a challenge to animal, environmental, and human health alike. Raman spectroscopy has the potential to provide for the rapid identification and screening of antimicrobial susceptibility of Klebsiella isolates. Moreover, hypervirulent isolates linked with extraintestinal infections express phenotypes that may support their niche adaptation. In this review, the prevalence, reservoirs, AMR, Raman spectroscopy detection, and pathogenicity of K. pneumoniae are summarized and various extraintestinal infection pathways are further narrated to extend our understanding of its adaptation and survival ability in reservoirs, and associated disease risks.

In this study, we used UPLC–MS/MS to determine diosmetin-7-o-β-d-glucoside in rat plasma and investigated its pharmacokinetics in rats. Six rats were given diosmetin-7-o-β-d-glucoside (5 mg/kg) by intravenous (i.v.) administration. The blood (150 μL) was withdrawn from the caudal vein after administration. Diazepam was used as an internal standard (IS), and a one-step acetonitrile precipitation method was used to process the plasma samples. Chromatographic separation was achieved using a UPLC BEH C18 column using a mobile phase of acetonitrile–0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization was applied, 463.1 → 301.0 for diosmetin-7-o-β-d-glucoside,m/z285.1 → 193.0 for diazepam (IS). Intra-day and inter-day precision of diosmetin-7-o-β-d-glucoside in rat plasma were less than 14%. The method was successfully applied in the pharmacokinetics of diosmetin-7-o-β-d-glucoside in rats after intravenous administration. Thet1/2of diosmetin-7-o-β-d-glucoside is 1.4 ± 0.4 h, which indicates the quick elimination.

Palmatine is a compound with good water solubility extracted from Coptis chinensis, Fibraurea recisa Pierre, Cortex Phellodendri Chinensis. Palmatine has good antibacterial activity and mainly used for the treatment of bacterial dysentery, gynecological inflammation, surgical infection, and conjunctivitis. It has anti-diabetic, anti-oxidant, and cognitive-enhancing activities. In this study, we used UPLC-MS/MS to determinate palmatine in rat plasma, and investigated its pharmacokinetics. Coptisine was utilized as an internal standard (IS), and acetonitrile precipitation method was used to process the plasma samples. Chromatographic separation was achieved using a UPLC BEH C18 column using mobile phase of acetonitrile- 0.1% formic acid with gradient elution. Electrospray ionization (ESI) tandem mass spectrometry in multiple reaction monitoring (MRM) mode with positive ionization was applied. The results indicated that within the range of 1–500 ng/mL, linearity of palmatine in rat plasma was acceptable (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Intra-day and inter-day precision RSD of palmatine in rat plasma were less than 14%. Accuracy range was between 93.7 and 107.1%, and matrix effect was between 101.6 and 109.4%. The method was successfully applied in the pharmacokinetics of palmatine in rats after oral and intravenous administration. The absolute bioavailability of the palmatine was 15.5% in rats.

The jobs–housing balance and urban spatial structure are naturally connected, and understanding the connection is important for urban planning, geography, and transport studies. Using smartcard data in Beijing and Shanghai, this research employs a comparative approach to reveal spatial distribution patterns of jobs–housing balance in terms of transit commuters and derive the implied urban spatial structures for the two megacities in China. Results suggested that (1) the overall job–resident ratios estimated with smartcard data were 1.97 and 2.47 in Shanghai and Beijing, respectively; (2) compared to Beijing, Shanghai had greater intermixing of jobs and housing; (3) Beijing’s urban form followed a concentric spatial structure, whereas Shanghai followed a quasi-sector configuration. These findings show that the job–resident ratio can be used as an indicator to capture land-use patterns or functional zones, which is useful for urban planning and transit network design.

The Florida sandhill crane Antigone canadensis pratensis is designated as threatened by the state of Florida, where there is an urgent need to map and quantify available habitat. First, we used habitat suitability index (HSI) modelling to map and assess potential nesting habitat for sandhill cranes in Florida. Second, we used spatial optimization approaches to calculate the maximum number of breeding pairs that can simultaneously occupy potential nests given that they both must be of some minimum quality and must be spaced some minimal distance apart. Mapping results reveal that nesting habitat is concentrated in the central portion of the state, with adequate brooding habitat appearing to be the most limiting factor affecting habitat suitability. Assuming nesting only occurs in habitat rated as high quality (HSI ≥ 0.7) and spacing between adjacent nests is ≥1,000 m, we conservatively estimate that 5,540 nesting pairs of Florida sandhill cranes can potentially be supported. Additional nesting pairs may be supported in habitats of marginal (HSI ≥ 0.3; 14,530) to moderate (HSI ≥ 0.5; 8,723) quality. The suitability maps and breeding pair estimates can be used to identify important habitat areas to focus crane conservation efforts, determine potentially limiting habitat features across the landscape, and potentially guide future population monitoring efforts. For example, grassland or prairie restoration could be used to potentially increase nesting pairs in the southern portion of the state where emergent wetlands are abundant but brooding habitat is lacking.

Objective:Laboratory-based characterization and traceback ofClostridium butyricumisolates linked to outbreak cases of neonatal necrotizing enterocolitis (NEC) in a hospital in China.Methods:In total, 37 samples were collected during the NEC outbreak. Classical bacteriological methods were applied to isolate and identifyClostridiumspp. Meanwhile, 24 samples collected after an outbreak were similarly tested. AllClostridiumisolates were identified to species level as eitherC. butyricumorC. sporogenes. These isolates were subsequently subtyped using pulsed-field gel electrophoresis (PFGE). Genomic DNA was purified from 2 representativeC. butyricumisolates and sequenced to completion.Results:Of 37 samples collected during the NEC outbreak, 17 (45.95%) were positive forClostridiumspp. One species,C. butyricum, was cultured from 10 samples. Another species cultured from 2 other samples was identified asC. sporogenes. Both of these species were cocultured from 5 samples. Pulsotyping showed that the 15C. butyricumand the 7C. sporogenesisolates produced indistinguishable DNA profiles. No NEC cases were reported after disinfection following the outbreak, and all samples collected after the outbreak were negative forClostridiumspp. Whole-genome sequencing (WGS) indicated that sialidase, hemolysin, and enterotoxin virulence factors were located on the chromosomes of 2C. butyricumisolates.Conclusions:The outbreak of NEC was epidemiologically linked toC. butyricumcontamination within the hospital. This is the first report of an NEC outbreak associated withC. butyricuminfection in China.

Immune checkpoint inhibitors (ICIs) are a revolutionary breakthrough in the field of cancer by modulating patient’s own immune system to exert anti-tumor effects. The clinical application of ICIs is still in its infancy, and their dosing regimens need to be continuously adjusted. Pharmacokinetic/pharmacodynamic studies showed a significant plateau in the exposure-response curve, with high receptor occupancy and plasma concentrations achieved at low dose levels. Coupled with concerns about drug toxicity and heavy economic costs, there has been an ongoing quest to reevaluate the current ICI dosing regimens while preserving maximum clinical efficacy. Many clinical data showed remarkable anticancer effects with ICIs at the doses far below the approved regimens, indicating the possibility of dose reduction. Our review attempts to summarize the clinical evidence for ICIs regimens with lower-dose, less-frequency, shorter-course, and provide clues for further ICIs regimen optimization.

Electrical control of spin transport at single molecule level is highly desired for molecular nanospintronics. By exploiting magnetic bistability of spin crossover complexes, the magnitude of spin polarization can be modulated. However, efficiently controlling the direction of spin polarization at single molecule level is still challenging. Here, we propose a general method to flip the transport electron spin simply by electrical gating in single molecule devices based on bipolar magnetic molecules (BMMs), of which the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) come from different spin channels. Thus, when the device's Fermi level is reversibly adjusted approaching either HOMO or LUMO by changing the polarity of the applied voltage gate, a 100 % spin polarized current with switchable spin direction is achievable. The proposed method is verified by the calculated electronic and transport properties of 9 potential transition metal coordination BMMs.

Background: Type 2 diabetes (T2D) is considered as one of the most significant metabolic syndromes worldwide, and the long-term use of the drugs already on the market for T2D often gives rise to some side effects. The mulberry leaf (ML), Morus alba L., has advantages in terms of its comprehensive therapeutic efficacy, which are characterized as multicomponent, multitarget, multipathway, and matching with the complex pathological mechanisms of diabetes.Methods: T2D rats were established by a high-fat diet combined with an intraperitoneal injection of streptozotocin; an evaluation of the hypoglycemic effects of the ML in combination with fasting blood glucose and other indicators, in addition to the utilization of metabolomics technology, was performed to analysis the metabolite changes in serum of rats.Results: MLs significantly reduced the fasting blood glucose of T2D rats, while improving the symptoms of polyphagia and polyuria. ML treatment altered the levels of various metabolites in the serum of T2D rats, which are involved in multiple metabolic pathways (amino acid metabolism, carbohydrate metabolism, and lipid metabolism), played a role in antioxidative stress and anti-inflammation, modulated immune and gluconeogenesis processes, and improved obesity as well as insulin resistance (IR).Conclusion: The ML contains a variety of chemical components, and metabolomic results have shown that MLs regulate multiple metabolic pathways to exert hypoglycemic effects, suggesting that MLs may have great promise in the development of new hypoglycemic drugs.

Plant growth and yield are adversely affected by soil salinity. PGPRs can promote plant growth and enhance plant tolerance to salt stress.

Migraine is a major cause of disability worldwide, particularly in young adults and middle-aged women. Xiongshao Zhitong Recipe (XZR) is a traditional Chinese medicine prescription used for treating migraine, but its bioactive components and therapeutic mechanisms remain unclear. We aimed to confirm the therapeutic effect of XZR on migraine and to determine the possible mechanism and bioactive components of XZR. Here, a sensitive UHPLC-LTQ-Orbitrap MS assay was carried out to analyze the ingredients of XZR, and a total of 62 components were identified, including coumarins, phenolic acids, phthalides, flavonoids, and terpenoids; among them, 15 components were identified in the serum samples after XZR treatment. We established a rat model of migraine

Objective. To investigate the emotional response, stress and psychological changes of patients with breast cancer after surgery for psychological intervention-assisted comfort nursing based on the PERMA model. Methods. A total of 100 postoperative breast cancer patients admitted to our hospital from March 2019 to June 2021 were selected as prospective research objects. According to a random number table, they were divided into a control group and an observation group with 50 cases each. Among them, the control group implemented routine nursing care, and the observation group implemented psychological intervention-assisted comfort care based on the PERMA model on the basis of the control group. The differences in compliance behavior, self-care ability, emotional response, stress response changes, and pain scores of the two groups of breast cancer patients before and after nursing were compared. Results. After nursing, the mental behavior scores, exercise scores, medication scores, and balanced diet scores of the two groups of breast cancer patients after surgery were significantly improved. The observation group’s compliance behavior scores were significantly higher than those of the control group. In the two groups of breast cancer patients, postoperative anxiety, depression, fatigue, and anger of the patients were significantly improved, and the emotional response score of the observation group was significantly lower than that of the control group. The self-care skill score, self-responsibility score, health knowledge score, and self-concept score of the observation group were excellent compared with those of the control group; the difference was significant by the above statistics ( P < 0.05 ). The HR and MAP of the control group during the operation were higher than those 1 day before the start of the operation and decreased at the end of the operation, but still higher than the level 1 day before the start of the operation; the change trend of the observation group was the same as that of the control group, but there were differences between the time points. There was no significant significance ( P > 0.05 ). The HR and MAP of the observation group during the operation were lower than those of the control group, and the MAP at the end of the operation was lower than that of the control group. This difference was statistically significant ( P < 0.05 ). In the control group, the values increased at the time point during the operation and decreased at the end of the operation, but still higher than the level 1 day before the operation. The difference was statistically significant ( P < 0.05 ). The change trend of the observation group was the same as that of the control group; and the values during and at the end of the operation were all lower than those of the control group. This difference was statistically significant ( P < 0.05 ). The pain scores of the two groups of patients at different time points were significantly improved, and the observation group was significantly less than the control group. This difference was statistically significant ( P < 0.05 ). Conclusion. Psychological intervention-assisted comfort nursing can effectively enhance the compliance behavior of patients after breast cancer surgery, improve the emotional response, stress response, and pain of patients, and have certain reference value for the nursing of patients after breast cancer surgery.

The number of spent lithium-ion batteries (LIBs) will increase exponentially in the coming decade with the retirement of electric vehicles (EVs). There is a knowledge gap in assessing the environmental impact of different terminal disposal paths for EV LIBs in China. Here, we take representative lithium iron phosphate (LFP) power batteries as example and carry out a bottom-up life cycle assessment (LCA). The life cycle stages of battery manufacturing, use, second life and battery recycling are considered to conduct a cradle-to-grave environmental impact analysis. To investigate the environmental benefits of end-of-life (EoL) stage for LFP batteries, two EoL management scenarios are considered in this study. The first one combines second life application with battery recycling, and the second recycles the retired batteries directly after EV use. The result shows that the secondary application of retired LFP batteries in energy storage systems (ESSs) can effectively reduce the net environmental impact of LIB life cycle, especially for fossil fuel depletion. When the service life of secondary use is increased from 1 year to 10 years, the environmental benefits of different impact categories will increase by 0.24-4.62 times. For direct recycle scenario, recycling retired LFP batteries can save more than 30% of metal resources. By comparison, we find that recycling lithium nickel manganese cobalt oxide (NCM) batteries has greater environmental benefits than recycling LFP batteries for all impact categories. When considering the environmental benefits at the EoL stage, most life cycle environmental impact is likely to be offset or even show positive benefits if more than 50% of power batteries can be reused in ESSs after retirement.