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Abstract Background Prehabilitation is a crucial component of tumor rehabilitation that attempts to improve patients’ preoperative health, although its efficacy in treating patients with cancers of the digestive system is still up for debate. Methods The records from PubMed (MEDLINE), Embase, Web of Science, Cochrane Library, EBSCO, Scopus, CNKI and Wan fang database up to November 2024 were systematically searched. The Cochrane Collaboration tool was employed for evaluating the risk of bias in each study, and the PRISMA 2020 checklist provided by the EQUATOR network was utilized. Results Through quality analysis, 20 articles were included, involving 1719 patients. Although its effect on severe complications is still unknown, the prehabilitation significantly decreased overall postoperative complications when compared to standard care, with a risk ratio (RR) of 0.74 (95% CI: 0.65 to 0.84). Despite not shortening the postoperative hospital stay (MD: -0.13, 95% CI: -0.29 to 0.03), prehabilitation demonstrated notable improvements in the 6-minute walk distance (6MWD), with preoperative gains (MD: 25.87, 95% CI: 14.49 to 37.25) and sustained benefits at 4 weeks postoperatively (MD: 22.48, 95% CI: 7.85 to 37.12). However, no significant differences in 6MWD were observed at 6 or 8 weeks postoperatively. The average improvement in 6MWD from baseline to preoperative was 28.99 (95% CI: 10.89 to 47.08, P = 0.002), and from 4 weeks postoperative to baseline, it was 25.95 (95% CI: 6.84 to 45.07, P = 0.008), with no significant change at 8 weeks. The acceptance and completion rates of prehabilitation were commendably high at 61% (95% CI: 47–75%) and 90% (95% CI: 87–93%), respectively, alongside a relatively low dropout rate of 10% (95% CI: 7% to13%). Conclusions Prehabilitation reduces postoperative complications and improves short-term physical function in digestive surgery patients, with good patient acceptance; however, the long-term effects are unknown due to a lack of follow-up data. Registration It was registered with the International Prospective Register of Systematic Reviews (PROSPERO) with the identification code CRD42022361100.

Abstract Family socioeconomic status (SES) is one of the key indicators of academic achievement, including language achievement. Further investigation of SES’s mechanisms of influence and potential mediators is essential due to the concern regarding the disparities caused by SES in language achievement. This study examines the relation between SES and Chinese adolescents’ English achievement, emphasizing the role of parenting as a conduit for socioeconomic impacts on children and adolescents. The mechanism through which SES influences English achievement was examined in a sample of 1634 junior secondary school students in an urban city in mainland China. A unified model with solid fit indices, comprising both SES and parenting components, was identified through structural equation modeling. As expected, socio-economic disparities appeared to be largely associated with students’ English achievement, and this connection was partially mediated by parental emotional support. Parental emotional support, however, had varied mediating effects that affected the developmental course and shaped achievement outcomes across different SES groups. This study offers valuable insights into the joint contribution of distal SES factors and proximal interactions to achievement outcomes. Intervention efforts and future research implications are discussed.

Abstract FKBP4, a member of the FK506-binding protein (FKBP) family, is a promising target for a variety of disorders, including cancer. However, its underlying molecular mechanism and potential function in hepatocellular carcinoma (HCC) are largely elusive. Therefore, we aimed to investigate the expression status, functional implications and underlying mechanisms of FKBP4 in HCC. Our bioinformatics analysis of TCGA LIHC datasets, ICGC LIRI-JP datasets and GEO datasets results showed FKBP4 was upregulated in HCC tissues. We also confirmed the elevated FKBP4 in clinical HCC samples. Additionally, quantitative RT-PCR results revealed FKBP4 was highly expressed in all five tested HCC cell lines. We also observed a correlation between elevated FKBP4 expression and poor prognosis in HCC patients. Loss of FKBP4 can inhibit the proliferation and migration in HCC cells. Furthermore, we found that silencing FKBP4 suppressed glucose uptake, lactic acid production and 18F-FDG uptake compared with the control group. Mechanistically, our funding indicated that FKBP4 participates in glycolysis through p53 mediated HK2 signaling pathway, specially, FKBP4 knockdown promotes the expression and stability of p53 protein rather than affecting the transcription level. Finally, rescue experiments revealed that simultaneous knockdown of both FKBP4 and p53 partially reversed the inhibitory effects on HK2 protein levels and 18F-FDG uptake. Our study elucidates a novel role of FKBP4 in promoting HCC development and glycolysis by modulating the p53/HK2 signaling pathway. Given the critical role of aerobic glycolysis in the progression of HCC, targeting FKBP4 may offer a new therapeutic strategy for treating this malignancy.

This is an article in the field of metallurgical engineering. Torecover copper and iron from a copper smelting slag flotation tailingwith iron grade of 37.42% and copper grade of 1.86%, according to the characteristics of its ore properties, the bituminous coal was used as a reductant, the process of direct reduction roasting - magnetic separation was applied.The experimental results show that copper smelting slag, bitumite and quicklime (as a co-reducing agent) are mixed in the mass ratio of 100∶25∶20, and at the conditions of roasting temperature of 1 200 ℃, time of 80 min, the roasted ores gringding fineness of -0.045 mm 80%, and magnetic strength of 0.139 T, the copper-bearing iron ore concentrate can be obtained with an iron grade of 90.98%, iron recovery of 90.13%, copper grade of 5.82% and copper recovery of 87.38%, thus realizing the comprehensive recovery of copper and iron from copper smelting slags.

Fibrosis, neurodegeneration, and cerebral angiomatosis (FINCA) syndrome is an autosomal recessive genetic disorder caused by mutations in NHL-repeat-containing protein 2 (NHLRC2) gene. This case report describes two Chinese siblings with FINCA syndrome carrying a novel frameshift variant, c.1610dupT (p.L537Ffs*17), of NHLRC2 gene. They shared similar symptoms of interstitial lung disease (ILD) and neurodegeneration, with early onset during infancy, and shared similar chest CT findings of bilateral ground-glass opacities and consolidations. The elder brother died of infantile respiratory failure, while the younger brother showed improvement in respiratory symptoms, chest CT, and Krebs von den Lungen-6 levels after long-term systemic glucocorticoid therapy, indicating that anti-inflammatory treatment may be beneficial in the treatment of ILD caused by FINCA syndrome.

m6A methylation is the most frequent modification of mRNA in eukaryotes and plays a crucial role in cancer progression by regulating biological functions. Insulin-like growth factor 2 mRNA-binding proteins (IGF2BP) are newly identified m6A ‘readers’. They belong to a family of RNA-binding proteins, which bind to the m6A sites on different RNA sequences and stabilize them to promote cancer progression. In this review, we summarize the mechanisms by which different upstream factors regulate IGF2BP in cancer. The current literature analyzed here reveals that the IGF2BP family proteins promote cancer cell proliferation, survival, and chemoresistance, inhibit apoptosis, and are also associated with cancer glycolysis, angiogenesis, and the immune response in the tumor microenvironment. Therefore, with the discovery of their role as ‘readers’ of m6A and the characteristic re-expression of IGF2BPs in cancers, it is important to elucidate their mechanism of action in the immunosuppressive tumor microenvironment. We also describe in detail the regulatory and interaction network of the IGF2BP family in downstream target RNAs and discuss their potential clinical applications as diagnostic and prognostic markers, as well as recent advances in IGF2BP biology and associated therapeutic value.

Gastric cancer (GC) is a common malignant tumor that is pernicious to the health of patients. Proteasome activator subunit 3 (PSME3) has been shown to exhibit higher expression and aggravate tumorigenesis in cancer progression. A major finding is that PSME3 is also highly expressed in GC tissues, which results in a worse prognosis. Nevertheless, the regulatory functions of PSME3 in GC progression remain unclear. This study aimed to investigate the impacts of PSME3 and related regulatory pathways on GC progression. From the Gene Expression Profiling Interactive Analysis (GEPIA) database, it was noted that PSME3 expression was up-regulated in GC tissues. Our findings suggested that in GC, PSME3 showed higher expression, resulting in a worse prognosis. Functional experiments revealed that PSME3 accelerates cell growth, migration and abnormal glycolysis in GC. PSME3 stimulates the epidermal growth factor receptor (EGFR)/c-myc pathway. In conclusion, GC cells exhibited higher PSME3 expression, which modulated the EGFR/c-myc pathway to facilitate glycolysis and migration. PSME3 might be an effective bio-target for GC treatment.

Background: Previous research on the prognostic implications of left ventricular myocardial strain using cardiac magnetic resonance feature tracking (CMR-FT) in light-chain cardiac amyloidosis (AL-CA) has shown promising potential. This study aimed to evaluate the prognostic significance of global and segmental left ventricular myocardial strain in AL-CA patients, specifically analyzing the American Heart Association's 16 segments. Methods: A total of 75 consecutive patients (50 men, mean age: 55.6 ± 10.0 years) who underwent CMR examination with histologically confirmed systemic AL-CA were retrospectively enrolled between January 2014 and November 2022. Both global and segmental myocardial strain and the American Heart Association’s 16 segments were quantified using CMR-FT on the steady-state free precession (SSFP) cine sequence. A comparative analysis was conducted between survivors and non-survivors based on the defined endpoint. Student t-test or Mann–Whitney U, receiver operating characteristic curve, Kaplan–Meier event-free survival curve, and Cox proportional hazards regression were used. Significance was set at p < 0.05. Results: Following a median follow-up of 34 months, 16 out of 75 patients experienced mortality events. B-type natriuretic peptides (BNP) (p < 0.001), global radial strain (RSglobal) (p = 0.033), and RS in the basal inferior segment (RSbas-inferior) (p = 0.025) remained significant as independent predictors of all-cause mortality. The cut-off values were identified as 24.97% for RSglobal, and 20.97% for RSbas-inferior. Kaplan–Meier survival curves revealed significantly reduced event-free survival for individuals in the lower cut-off groups for RSglobal and RSbas-inferior (p = 0.013, p < 0.001, respectively). Conclusions: Radial strain for the global and the basal inferior segment may prove valuable for risk stratification in patients with AL-CA.

This is an essay in the field of mineral processing engineering. The main minerals in tantalum niobium tailings in Jiangxi Province are feldspar, quartz, lithionite and topaz, containing a small amount of spodumene and sericite, among which the main available minerals are lithionite. For a long time, the tailings lack a comprehensive utilization and recycling process. This test study studies the flotation test of the main available mineral lithium mica in the tailings, determines the reasonable beneficiation recovery process, and provides a technical basis for the comprehensive utilization of the tailings. According to the process mineralogy properties of the ore, the lithium mica was recovered. Through a series of flotation condition tests, HZ-00 and dodecylamine are used as the combination catcher, Na2CO3 is pH value adjustment agent, water glass as the inhibitor, the flotation process of "one coarse, one sweep and one fine", the flotation closed circuit test can obtain Li2O grade of 4.3.02%, the recovery rate of 72.41%, and the test results are relatively ideal.

Abstract Background Group 2 innate lymphoid cells (ILC2s) are critical sources of type 2 cytokines and represent one of the major tissue-resident lymphoid cells in the mouse lung. However, the molecular mechanisms underlying ILC2 activation under challenges are not fully understood. Results Here, using single-cell transcriptomics, genetic reporters, and gene knockouts, we identify four ILC2 subsets, including two non-activation subsets and two activation subsets, in the mouse acute inflammatory lung. Of note, a distinct activation subset, marked by the transcription factor Nr4a1, paradoxically expresses both tissue-resident memory T cell (Trm), and effector/central memory T cell (Tem/Tcm) signature genes, as well as higher scores of proliferation, activation, and wound healing, all driven by its particular regulons. Furthermore, we demonstrate that the Nr4a1+ILC2s are restrained from activating by the programmed cell death protein-1 (PD-1), which negatively modulates their activation-related regulons. PD-1 deficiency places the non-activation ILC2s in a state that is prone to activation, resulting in Nr4a1+ILC2 differentiation through different activation trajectories. Loss of PD-1 also leads to the expansion of Nr4a1+ILC2s by the increase of their proliferation ability. Conclusions The findings show that activated ILC2s are a heterogenous population encompassing distinct subsets that have different propensities, and therefore provide an opportunity to explore PD-1's role in modulating the activity of ILC2s for disease prevention and therapy.

Abstract This study aims to investigate the effectiveness of umbilical cord mesenchymal stem cells (UCMSCs) in treating osteoarthritis (OA). Sprague–Dawley rats were used in in vivo experiments and divided into four groups: normal, OA model, saline, and UCMSC-treated groups (n = 6). An OA model was established by injecting iodoacetic acid into the joint cavity. The results indicate that UCMSC transplantation significantly reduced joint surface and articular cartilage damage, and the levels of IL-1β, TNF-α, and MMP13 in the joint fluid were significantly reduced after UCMSC treatment. In vitro experiments showed that co-culturing UCMSCs and chondrocytes promoted the expression of aggrecan, COL2, SOX9, and BCL-2; downregulated the expression of BAX and BAD in chondrocytes; and promoted the expression of IL-10 and TGF-β1 in UCMSCs. Additionally, the supernatant of UCMSCs inhibited the expression of IL-1β and TNF-α in the articular cavity and promoted the expression of COL2 and aggrecan in vivo. These effects were impaired when IL-10 and TGF-β1 were removed. Collectively, UCMSC transplantation appears to improve joint pathology, reduce inflammatory factors, and decrease chondrocyte apoptosis, likely through the involvement of IL-10 and TGF-β1, thus providing a potential therapeutic option for patients with OA.

The world is confronted with increasing droughts exacerbated by the inefficiency of irrigation, and water-saving irrigation (WSI) holds the potential to alleviate this dilemma. Since individual farmers are important participants in WSI, it is imperative to account for their decision preferences. In addition, previous research did not consider the decision reverse in the intertemporal choice of WSI construction. Recognizing the presence of bounded rationality, particularly in terms of time preference inconsistency, a hyperbolic discounting model is constructed. The implicit subsidy, explicit subsidy, and improved explicit subsidy scenarios are simulated to analyze the decision process of individual farmers in WSI construction. The proposed methods are applied to discuss the construction of WSI within the Taocheng District, Hebei Province. The results show that: (1) The participation and stability of individual WSI construction demonstrated an increase in both the explicit subsidy and improved explicit subsidy. (2) Compared with the implicit subsidy, there was a 29.6% decrease in the number of participants who chose not to engage in WSI construction at different intertemporal choice points in the explicit subsidy scenario, and the inconsistency of choice in different intertemporal choice points decreased from 70.4% to 31.4%. (3) In the improved explicit subsidy scenario, the inconsistency of choice in different intertemporal choice points will be further reduced to 22.5%. In order to promote WSI construction for water conservation, the policy implications of the subsidy mechanism are proposed in this paper.

Background: Although umbilical cord mesenchymal stem cell (UCMSC) infusion has been proposed as a promising strategy for the treatment of acute lung injury (ALI), the parameters of UCMSC transplantation, such as infusion routes and doses, need to be further optimized. Methods: In this study, we compared the therapeutic effects of UCMSCs transplanted via intravenous injection and intratracheal instillation on lipopolysaccharide-induced ALI using a rat model. Following transplantation, levels of inflammatory factors in serum; neutrophils, total white blood cells, and lymphocytes in bronchoalveolar lavage fluid (BALF); and lung damage levels were analyzed. Results: The results indicated that UCMSCs administered via both intravenous and intratracheal routes were effective in alleviating ALI, as determined by analyses of arterial blood gas, lung histopathology, BALF contents, and levels of inflammatory factors. Comparatively, the intratracheal instillation of UCMSCs was found to result in lower levels of lymphocytes and total proteins in BALF, whereas greater reductions in the serum levels of tumor necrosis factor α (TNF-α) and interleukin 1β (IL-1β) were detected in rats receiving intravenously injected stem cells. Conclusions: Our findings in this study provide convincing evidence to indicate the efficacy of UCMSC therapy in the treatment of ALI mediated via different delivery routes, thereby providing a reliable theoretical basis for further clinical studies. Moreover, these findings imply that the effects obtained using the two assessed delivery routes for UCMSC transplantation are mediated via different mechanisms, which could be attributable to different cellular or molecular targets.

Collection of data in our Information Technology age caused a revolution in knowledge. The unprecedented growth of data in the big data era has necessitated changes in the scale, nature, and status of data, leading researchers to adopt new paradigms and methodologies in philosophical research. In particular, the theoretical focus of philosophy of language shifted towards cognitive knowledge, with an emphasis on the proposition of data turn in cognitive cognition in the era of big data. The paper explores the potential scope for quantitative research on the data turn of philosophy of language by examining the need for transforming qualitative and quantitative research paradigms, by reconstructing the quantitative approach to philosophy of language, and by expanding human-data relations in the philosophy of big data. The paper concludes that there is the necessity for further research to examine the relationship between language, data and philosophy.

As part of the genus Enteropathogenic Coronaviruses, Porcine Epidemic Diarrhea Virus (PEDV) is an important cause of early diarrhea and death in piglets, and one of the most difficult swine diseases to prevent and control in the pig industry. Previously, we found that PEDV can block Na+ absorption and induce diarrhea in piglets by inhibiting the activity of the sodium-hydrogen ion transporter NHE3 in pig intestinal epithelial cells, but the mechanism needs to be further explored. The epidermal growth factor receptor (EGFR) has been proved to be one of the co-receptors involved in many viral infections and a key protein involved in the regulation of NHE3 activity in response to various pathological stimuli. Based on this, our study used porcine intestinal epithelial cells (IPEC-J2) as an infection model to investigate the role of EGFR in regulating NHE3 activity after PEDV infection. The results showed that EGFR mediated viral invasion by interacting with PEDV S1, and activated EGFR regulated the downstream EGFR/ERK signaling pathway, resulting in decreased expression of NHE3 and reduced NHE3 mobility at the plasma membrane, which ultimately led to decreased NHE3 activity. The low level of NHE3 expression in intestinal epithelial cells may be a key factor leading to PEDV-induced diarrhea in newborn piglets. This study reveals the importance of EGFR in the regulation of NHE3 activity by PEDV and provides new targets and clues for the prevention and treatment of PEDV-induced diarrhea in piglets.

Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection.

Yuan-Ming Yuan Imperial Garden is a historically royal garden; it not only occupies an important position in the history of Chinese garden, but also enjoys a high reputation in the world.The historical and cultural values contained in Yuan-Ming Yuan Imperial Garden needs to be widely understood by the Chinese people and be remembered by the world through a new way.Focusing on the work policy for cultural relics of “protection first, strict management, mining value, rational utilization and good transmission”, a new solution of parallel Yuan-Ming Yuan Imperial Garden was proposed, which provided technical reference for the construction of the smart Yuan-Ming Yuan Imperial Garden.Parallel Yuan-Ming Yuan Imperial Garden is the application of ACP theory in the operation and management.Descriptive intelligence will be used to construct a virtual Yuan-Ming Yuan Imperial Garden, predictive intelligence will be used to conduct large-scale computational experiments in the virtual Yuan-Ming Yuan Imperial Garden, and prescriptive intelligence and parallel execution will be used to outbreak the geographical limit and lead to the smart management of Yuan-Ming Yuan Imperial Garden.It is expected that the development and enrichment of the Yuan-Ming Yuan Imperial Garden in the virtual world, and the increasingly parallel interaction and integration with the real world, will bring about a new operating mode.

Summary: Developing renewable energy could jointly reduce air pollution, greenhouse gas emissions, and bring air pollution-related health co-benefits. However, the temporal and sub-national distributions of investment costs and human health co-benefits from renewable energy deployment remain unclear. To investigate this gap, we linked multiple models for a more comprehensive assessment of the economic-environmental-health co-benefits of renewable energy development in China. The results show that developing renewable energy can avoid 0.6 million premature mortalities, 151 million morbidities, and 111 million work-loss days in 2050. Meanwhile, the human health and economic co-benefits vary substantially across regions in China. Renewable energy can undoubtedly bring health and economic co-benefits. Nevertheless, the economic benefits lag considerably behind the high initial investment cost, first negative in 2030 (−0.6 trillion Yuan) and then positive in 2050 (2.9 trillion Yuan). Hence, renewable energy deployment strategy must be carefully designed considering the regional disparities.

Quantifying regional health disparities linked to air pollution is essential for enhancing air quality and attaining carbon neutrality objectives. Nonetheless, the efficacy of proactive policies in ensuring equitable health protection in China’s Eastern Coastal Area (ECA) remains uncertain. Here, we employed an integrated assessment model to assess the combined reduction of carbon dioxide (CO _2 ) and atmospheric pollutants and their health repercussions in the ECA of China. Our findings reveal that 273 000 premature deaths are attributable to air pollution in 2060 in the ECA in the absence of mitigation policies. Conversely, carbon reduction policies are poised to curtail 80% of CO _2 emissions, alongside reductions of 76% for NO _x , 79% for SO _2 , 80% for PM _2.5 , 72% for VOCs, and 66% for NH _3 emissions. Air pollution control policies could mitigate premature deaths by 19 600, while carbon reduction policies could potentially lower them by 50 800. The health inequality coefficient among provinces stands at 0.19, primarily attributable to significantly higher mortality rates in Hebei and Shandong. These findings yield valuable insights for crafting synergistic abatement strategies in similarly imbalanced developmental regions grappling with comparable environmental challenges.

Abstract Background B1 cells are self-renewing innate-like B lymphocytes that provide the first line of defense against pathogens. B1 cells primarily reside in the peritoneal cavity and are known to originate from various fetal tissues, yet their developmental pathways and the mechanisms underlying maintenance of B1 cells throughout adulthood remain unclear. Results We performed high-throughput single-cell analysis of the transcriptomes and B-cell receptor repertoires of peritoneal B cells of neonates, young adults, and elderly mice. Gene expression analysis of 31,718 peritoneal B cells showed that the neonate peritoneal cavity contained many B1 progenitors, and neonate B cell specific clustering revealed two trajectories of peritoneal B1 cell development, including pre-BCR dependent and pre-BCR independent pathways. We also detected profound age-related changes in B1 cell transcriptomes: clear difference in senescence genetic program was evident in differentially aged B1 cells, and we found an example that a B1 subset only present in the oldest mice was marked by expression of the fatty-acid receptor CD36. We also performed antibody gene sequencing of 15,967 peritoneal B cells from the three age groups and discovered that B1 cell aging was associated with clonal expansion and two B1 cell clones expanded in the aged mice had the same CDR-H3 sequence (AGDYDGYWYFDV) as a pathogenically linked cell type from a recent study of an atherosclerosis mouse model. Conclusions Beyond offering an unprecedent data resource to explore the cell-to-cell variation in B cells, our study has revealed that B1 precursor subsets are present in the neonate peritoneal cavity and dissected the developmental pathway of the precursor cells. Besides, this study has found the expression of CD36 on the B1 cells in the aged mice. And the single-cell B-cell receptor sequencing reveals B1 cell aging is associated with clonal expansion.

Objective To investigate the ocular surface effects of different digital media experiences in Chinese elementary school students.Design Population-based cross-sectional study was used.Setting 14 randomly selected primary schools in Yuhuatai District, Nanjing, ChinaParticipants 2,694 students between 7 and 8-year-old.Outcome Measures Prevalence of and risk factors for different types of dry eye disease，and different digital media experience with different ocular signs.Results The prevalence of ‘symptomatic DED’ was 8.7% (95% CI 7.6% to 9.8%) and ‘definite DED’ prevalence rate was 5.5% (95% CI 4.7% to 6.4%). In multivariable logistic regression model, allergic conjunctivitis (OR=4.33, 95% CI (3.01 to 6.23), p

As a bio]diversity hotspot, the East Indies (Coral) Triangle possesses the highest biodiversity on the earth. However, evolutionary hypotheses around this area remain controversial; e.g., center of origin, center of accumulation, and center of overlap have been supported by different species. This study aims to answer the evolutionary influence of the Indonesian Seaway on the biodiversity of the Coral Triangle by recovering the evolutionary origins of a wide-ranging ommastrephid squid (Sthenoteuthis oualaniensis) based on integrated molecular and oceanographic clues from the Indo-Pacific. Three new clades were revealed; viz., clade I from the South China Sea, clade II from the northern East Indian Ocean, and clade III from the southern East Indian Ocean. These two Indian Ocean clades formed a monophyly closely related to clade IV from the Central-Southeast Pacific. Clade VI from the central Equatorial Pacific and clade V from the northern Eastern Pacific sit in basal positions of phylogenetic trees. Ancestral Sthenoteuthis was inferred to have originated from the Atlantic Ocean and sequentially dispersed to the northern East Pacific, central Equatorial Pacific, and West Pacific through the open Panama Seaway and being transported by westward North Equatorial Current. The East Indian Ocean was likely colonized by an ancestral population of clade IV from the Southeast Pacific. Westward South Equatorial Circulation could have promoted transoceanic migration of S. oualaniensis through the wide paleo-Indonesian Seaway. Sea level regression since the Miocene and the closure of the Indonesian Seaway at 4–3 Ma were responsible for the population genetic differentiation of S. oualaniensis in the Indo-Pacific. Therefore, the Indonesian Gateway played an important role in influencing marine organisms’ migration and population differentiation through controlling and reorganizing circulations in the Indo-Pacific.

The potent cytotoxic property of Vγ2Vδ2 T cells makes them attractive for adoptive T cell transfer therapy. The transfusing of the expanded Vγ2Vδ2 T cells into cancer patients shows well-tolerated, but the clinical response rates are required to be improved, implying that there is still an unmet efficacy with low toxicity for this novel anti-tumor therapy. In this study, we test the anti-tumor efficacy of a Y-body-based bispecific antibody (bsAb) Vγ2 x PD-L1 that preferentially redirects Vγ2Vδ2 T cells to combat PD-L1 positive tumor cells. With nanomolar affinity levels to Vγ2Vδ2 T cells and PD-L1+ tumor cells, Vγ2 x PD-L1 bridges a Vγ2Vδ2 T cell with a SKOV3 tumor cell to form a cell-to-cell conjugation. In a PD-L1-dependent manner, the bsAb elicits effective activation (CD25+CD69+), IFNγ releasing, degranulation (CD107a+), and cytokine production (IFNγ+ and TNFα+) of expanded Vγ2Vδ2 T cells. The activations of the Vγ2Vδ2 T cells eliminate PD-L1-expressing human cancer cell lines, including H1975, SKOV3, A375, H1299, and H2228 cells, but not PD-L1 negative cells including HEK-293 (293) cells and healthy PBMCs. Finally, we show that combining Vγ2 x PD-L1 with adoptively transferring Vγ2Vδ2 T cells inhibits the growth of existing tumor xenografts and increases the number of Vγ2Vδ2 T cells into the tumor bed. Vγ2 x PD-L1 represents a promising reagent for increasing the efficacy of adoptively transferred Vγ2Vδ2 T cells in the treatment of PD-L1 positive malignant tumors.

ObjectiveThe aim was to investigate the distribution and correlation of Ca, Mg, Zn, Cu, Fe, Pb, and Cd in the blood of children aged 0–14 years in Hunan, China, which may serve to provide a basis for clinical guidance on child health.Study DesignA retrospective analysis was carried out. Concentrations of all elements were determined by atomic absorption spectrophotometry. Distributions were analyzed and compared among different age, sex, and year groups by the Kruskal–Wallis test, the chi-square test, and the Fisher's exact test. Spearman's rank correlation coefficient was used to evaluate the association between every pair of elements.ResultsA total of 46,951 children were involved in this study from 2013 to 2019. The median blood levels of elements were 13.51 μmol/L (Cu), 58.69 μmol/L (Zn), 1.70 mmol/L (Ca), 1.40 mmol/L (Mg), 7.46 mmol/L (Fe), 35.00 μg/L (Pb), and 1.00 μg/L (Cd). Girls had a higher level of Ca and lower levels of Pb and Cd than boys. Cu and Ca showed an upward trend, and Mg and Pb showed a downward trend by year. Zn and Fe increased and Ca decreased significantly with age. The deficiency rates of Fe and Zn decreased significantly by year, while Ca and Cu increased significantly by year. Cd exposure in this area was relatively low.ConclusionMost children had normal levels of the essential elements Ca, Cu, and Mg and the toxic elements Pb and Cd. Severe deficiencies in Zn and Fe were observed in the relatively younger children but improved with age. Persistent efforts in reducing Pb exposure might still be needed.

Of the many possible individual factors bearing on test preparation, one is how individuals’ motivational and cognitive perceptions affect test-driven preparation practices. This study reports an investigation into test preparation of a high-stakes writing test from the perspective of expectancy-value theory. Undergraduate students (n = 623) on their test preparation for the writing tasks of China’s Graduate School Entrance English Examination (GSEEE) were recruited voluntarily from 11 universities in mainland China. The perceptions of GSEEE test takers, which included goal, task value, task demand, and expectation of success, were identified. Five types of preparation practices were identified for the GSEEE writing tasks: memorizing practice, test familiarization, comprehensive learning, skills development and drilling practice. Structural equation modeling revealed that the expectancy-value model held up well for the paths from test takers’ perceptions to test-driven preparation practices, which were not construct-oriented but goal-motivated. The GSEEE test takers’ goal, determined by the high-stakes nature of admission test, explained their motivation and determined their behavior toward test preparation. Results also indicated that task demand was inadequate to be termed a strong factor in affecting test preparation. As such, the findings of this study offer evidence regarding how an expectancy-value model fit into test preparation mechanism and provide insights into the nature and scope of test preparation for high-stakes writing tests.

Various coronaviruses have emerged as a result of cross-species transmission among humans and domestic animals. Porcine epidemic diarrhea virus (PEDV; family Coronaviridae, genus Alphacoronavirus) causes acute diarrhea, vomiting, dehydration, and high mortality in neonatal piglets. Porcine small intestinal epithelial cells (IPEC-J2 cells) can be used as target cells for PEDV infection. However, the origin of PEDV in pigs, the host range, and cross-species infection of PEDV remain unclear. To determine whether PEDV has the ability to infect human cells in vitro, human small intestinal epithelial cells (FHs 74 Int cells) were inoculated with PEDV LJX and PEDV CV777 strains. The results indicated that PEDV LJX, but not PEDV CV777, could infect FHs 74 Int cells. Furthermore, we observed M gene mRNA transcripts and N protein expression in infected FHs 74 Int cells. A one-step growth curve showed that the highest viral titer of PEDV occurred at 12 h post infection. Viral particles in vacuoles were observed in FHs 74 Int cells at 24 h post infection. The results proved that human small intestinal epithelial cells are susceptible to PEDV infection, suggesting the possibility of cross-species transmission of PEDV.

In order to fully understand and analyze the rules and cognitive characteristics of users’ learning methods and, with the assistance of Internet and artificial acquaintance technology, to emphasize the integrity and degree of personalized education, a personalized graph-learning-based recommendation system including user portraits is proposed. System raking of data layers, data analysis responses, and recommendations for sum beds are seamless and collaboratively combined. The data layer consists of user data and a design library containing scholarship materials, study materials, and price sets. The data analysis framework is captured by rest and energy data represented by basic information, learning behavior, etc. We can provide perceptual and visual learning audio feedback. And thus witness computing should convey users’ learning behavior rules through similarity analysis and mob algorithm. We further use TF-IDF to sequentially mine users’ resource priorities and always bind personalized learning suggestions. The system has been applied to an online education platform supported by artificial intelligence technique, which can provide instructors and students with personalized portraits. We also proposed to learn audio feedback and data consulting services, typically during the hard work phase of the assistant semester.

Strengthening construction for teaching staff is an eternal theme of development and construction for colleges, and it is also the focus of personnel management in colleges. China is swiftly transitioning from the industrial age to the era of intelligence as a result of the rapid growth of information technology and artificial intelligence. Colleges and universities have reached a new stage in their evolution, one marked by intelligent use of technology, as represented by the fourth generation of information technology: cloud computing, big data, and artificial intelligence. Higher standards for college professors’ teaching abilities have been imposed by this new policy. It is therefore beneficial to evaluate teachers’ teaching abilities from an artificial intelligence perspective to improve the overall quality of college education. First, this work researches and improves the teaching ability training strategies of college teachers driven by artificial intelligence from different levels. Second, this work proposes a neural network (IPSO-BP) for evaluating the teaching ability of college teachers via artificial intelligence technology. Aiming at the issues in BP network, this work constructs IPSO by improving the weight decay strategy and learning factor of PSO algorithm. Then, it uses IPSO to optimize the BP to construct IPSO-BP. Third, the results of the experiments in this work suggest that the strategy proposed here is both feasible and preferable.

Vγ2Vδ2 T cell-based immunotherapy has benefited some patients in clinical trials, but the overall efficacy is low for solid tumor patients. In this study, a bispecific antibody against both PD-L1 and CD3 (PD-L1 x CD3), Y111, could efficiently bridge T cells and PD-L1 expressing tumor cells. The Y111 prompted fresh CD8+ T cell-mediated lysis of H358 cells, but spared this effect on the fresh Vδ2+ T cells enriched from the same donors, which suggested that Y111 could bypass the anti-tumor capacity of the fresh Vγ2Vδ2 T cells. As the adoptive transfer of the expanded Vγ2Vδ2 T cells was approved to be safe and well-tolerated in clinical trials, we hypothesized that the combination of the expanded Vγ2Vδ2 T cells with the Y111 would provide an alternative approach of immunotherapy. Y111 induced the activation of the expanded Vγ2Vδ2 T cells in a dose-dependent fashion in the presence of PD-L1 positive tumor cells. Moreover, Y111 increased the cytotoxicity of the expanded Vγ2Vδ2 T cells against various NSCLC-derived tumor cell lines with the releases of granzyme B, IFNγ, and TNFα in vitro. Meanwhile, the adoptive transferred Vγ2Vδ2 T cells together with the Y111 inhibited the growth of the established xenografts in NPG mice. Taken together, our data suggested a clinical potential for the adoptive transferring the Vγ2Vδ2 T cells with the Y111 to treat PD-L1 positive solid tumors.

Objective To investigate the association between the solute carrier family 6 member 4 ( SLC6A4 ) gene L/S polymorphism and pulmonary arterial hypertension (PAH). Methods The relevant literature was retrieved from the PubMed® database and the data were extracted. STATA® version 12.0 software was used to calculate pooled odds ratios (ORs) and 95% confidence intervals (CI). Results Eight case–control studies qualified for inclusion in the meta-analysis. These studies included 1215 cases and 936 control subjects. There was no significant association between the SLC6A4 gene L/S polymorphism and PAH risk in the total population (LL versus SS: OR 1.83, 95% CI 0.95, 3.51; LS versus SS: OR 1.37, 95% CI 0.93, 2.02; dominant model: OR 1.38, 95% CI 0.97, 1.97; recessive model: OR 1.54, 95% CI 0.84, 2.83). Subgroup analysis based on study quality scores and Hardy–Weinberg equilibrium also showed no significant association. Conclusion The findings of this meta-analysis suggest that the SLC6A4 gene L/S polymorphism is unlikely to be related to PAH risk. Well-designed studies with more participants will be required to validate these results.

Recombinant tissue plasminogen activator (rt-PA) is used to treat acute ischemic stroke but is only effective if administered within 4.5 h after stroke onset. Delayed rt-PA treatment causes blood-brain barrier (BBB) disruption and hemorrhagic transformation. The compound 2-(-2-benzofuranyl)-2-imidazoline (2-BFI), a newly discovered antagonist of high-affinity postsynaptic N-methyl-D-aspartate (NMDA) receptors, has been shown to have neuroprotective effects in ischemia. Here, we investigated whether combining 2-BFI and rt-PA can ameliorate BBB disruption and prolong the therapeutic window in a rat model of embolic middle cerebral artery occlusion (eMCAO). Ischemia was induced in male Sprague Dawley rats by eMCAO, after which they were treated with 2-BFI (3 mg/kg) at 0.5 h in combination with rt-PA (10 mg/kg) at 6 or 8 h. Control rats were treated with saline or 2-BFI or rt-PA. Combined therapy with 2-BFI and rt-PA (6 h) reduced the infarct volume, denatured cell index, BBB permeability, and brain edema. This was associated with increased expression of aquaporin 4 (AQP4) and tight junction proteins (occludin and ZO-1) and downregulation of intercellular adhesion molecule 1 (ICAM-1) and matrix metalloproteinases 2 and 9 (MMP2 and MMP9). We conclude that 2-BFI protects the BBB from damage caused by delayed rt-PA treatment in ischemia. 2-BFI may therefore extend the therapeutic window up to 6 h after stroke onset in rats and may be a promising therapeutic strategy for humans. However, mechanisms to explain the effects oberved in the present study are not yet elucidated.

Purpose: This study aimed to characterize the microvascular and structural changes in the macular that occur in white matter hyperintensities (WMH) using optical coherence tomographic angiography. We also aimed to explore the association between macular microvascular and structural changes with focal markers of brain tissue on MRI in WMH using the Fazekas scale.Methods: This study enrolled healthy participants who were stroke- and dementia-free. MRI was used to image the cerebral white matter lesions, and Fazekas scale was used to evaluate the severity of the white matter lesions. Optical coherence tomography angiography (OCT-A) was used to image the radial peripapillary capillaries (RPCs), macular capillary plexuses [superficial capillary plexus (SCP) and deep capillary plexus (DCP)] and thickness around the optic nerve head, peripapillary retinal nerve fiber layer (pRNFL).Results: Seventy-four participants were enrolled and divided into two groups according to their Fazekas score (Fazekas scores ≤ 1 and ≥2). Participants with Fazekas score ≥2 showed significantly reduced RPC density (P = 0.02) and DCP density (P = 0.012) when compared with participants with Fazekas score ≤ 1. Participants with Fazekas score ≥2 showed reduced pRNFL (P = 0.004) when compared to participants with Fazekas score ≤ 1. Fazekas scores were significantly associated with the pRNFL thickness (Rho = −0.389, P = 0.001), RPC density (Rho = −0.248, P = 0.035), and DCP density (Rho = −0.283, P = 0.015), respectively.Conclusions: Microvascular impairment and neuro-axonal damage are associated with the disease cascade in WMH. We have shown that RPC and DCP densities are significantly affected, and these impairments are associated with the severity of the disease and cognitive function. OCT-A could be a useful tool in quantifying the retinal capillary densities in WMH.

Abstract Background Methamphetamine (METH) is a psychostimulant with high abuse liability that affects the monoamine neurotransmitter systems, particularly the dopamine system. Currently there are no effective medications for the treatment of METH abuse to restore METH-induced dopaminergic dysfunction. The Jitai tablet (JTT), a commercial traditional Chinese medicinal preparation, has been shown to modulate the dopaminergic function both in heroin addicts and in morphine-dependent rats. The purpose of this study was to investigate, in a rodent model, whether JTT can protect against METH-induced neurotoxicity, and/or restore METH-damaged dopaminergic function. Methods Immunohistochemical staining and/or autoradiography staining were used to detect tyrosine hydroxylase (TH) expression in the substantia nigra, and to examine the levels of dopamine transporter (DAT), dopamine D2 receptor (D2R) and TH levels in the striatum. Using a stereotyped behavior rating scale, we evaluated the inhibitory effect of JTT on METH-induced behavioral sensitization. Results Repeated METH administration induced obvious stereotyped behavior and neurotoxicity on the dopaminergic system. Pre-treatment with JTT significantly attenuated METH-induced stereotyped responses, and interdicted METH-induced changes in the levels of DAT, D2R and TH expression. Treatment with JTT after METH administration restored DAT, D2R and TH expression to normal levels. Conclusions Our results indicated that JTT protects against METH-induced neurotoxicity and restores the dopaminergic function, and thus might be a potential treatment for the dopaminergic deficits associated with METH abuse.

Acute ischemic stroke is a serious disease that endangers human health. In our efforts to develop an effective therapy, we previously showed that the potent, highly selective inhibitor of soluble epoxide hydrolase called 1-trifuoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU) protects the brain against focal ischemia in rats. Here we explored the mechanism of TPPU action by assessing whether it could preserve blood-brain barrier integrity and reduce apoptosis in the brain during permanent middle cerebral artery occlusion in male Sprague-Dawley rats. TPPU administration at the onset of stroke and once daily thereafter led to smaller infarct volume and brain edema as well as milder neurological deficits. TPPU significantly inhibited the activity of soluble epoxide hydrolase and matrix metalloproteases 2 and 9, reducing 14,15-DHET levels, while increasing expression of tight junction proteins. TPPU decreased numbers of apoptotic cells by down-regulating the pro-apoptotic proteins BAX and Caspase-3, while up-regulating the anti-apoptotic protein BCL-2. Our results suggest that TPPU can protect the blood-brain barrier and reduce the apoptosis of brain tissue caused by ischemia.

Porcine epidemic diarrhea virus (PEDV) mainly invades the small intestine and promotes an inflammatory response, eventually leading to severe diarrhea, vomiting, dehydration, and even death of piglets, which seriously threatens the economic development of pig farming. In recent years, researchers have found that probiotics can improve the intestinal microenvironment and reduce diarrhea. At the same time, certain probiotics have been shown to have antiviral effects; however, their mechanisms are different. Herein, we aimed to investigate the inhibitory effect of Lactiplantibacillus plantarum supernatant (LP-1S) on PEDV and its mechanism. We used IPEC-J2 cells as a model to assess the inhibitory effect of LP-1S on PEDV and to further investigate the relationship between LP-1S, Ca2+, and PEDV. The results showed that a divalent cation chelating agent (EGTA) and calcium channel inhibitors (Bepridil hydrochloride and BAPTA-acetoxymethylate) could inhibit PEDV proliferation while effectively reducing the intracellular Ca2+ concentration. Furthermore, LP-1S could reduce PEDV-induced loss of calcium channel proteins (TRPV6 and PMCA1b), alleviate intracellular Ca2+ accumulation caused by PEDV infection, and promote the balance of intra- and extracellular Ca2+ concentrations, thereby inhibiting PEDV proliferation. In summary, we found that LP-1S has potential therapeutic value against PEDV, which is realized by modulating Ca2+. This provides a potential new drug to treat PEDV infection. [ABSTRACT FROM AUTHOR]