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This study investigates the impact of small water bodies on outdoor temperatures in their vicinity, using a campus located in the subtropical region of Taichung City, Taiwan, as the research subject. By employing on-site measurements and Computational Fluid Dynamics (CFD) simulations, we examined their temporal and spatial influence, as well as comparisons between actual measurements and software predictions. Key findings include the following: (1) Small water bodies exhibit discernible temperature-regulating effects on their surrounding areas. While the influence diminishes with distance, this attenuation is not stark, and is potentially constrained by the water body’s patch size. (2) Regulatory effects vary between day and night. In summer, temperature reductions of up to 3.5 °C (simulated) and 3.2 °C (measured) were observed. Conversely, in winter, daytime temperatures around water bodies may rise by up to 3.9 °C. (3) Discrepancies between CFD simulations and actual measurements, influenced by fluctuations in Global Horizontal Irradiation (GHI), range from +2.5 °C to −1.8 °C. During high GHI periods, measured values surpass simulations, whereas during low or zero GHI conditions, simulations exceed measurements. Moreover, high regression analysis R2 values validate the feasibility of CFD simulations for predicting water body-induced temperature changes. Insights from this study offer valuable guidance for urban planners and policymakers seeking sustainable urban climate management strategies.

The dysfunction of phospholipid metabolism enzymes and the change in membrane phospholipid composition are associated with insulin resistance, indicating that phospholipids play an important role in the regulation of insulin sensitivity. The reflection of phospholipid changes in blood might provide clues for both mechanism understanding and intervention. Using a targeted phospholipidomic approach, 199 phospholipid molecular species were identified and quantified in the plasma of 1053 middle-aged participants from a national investigation. The associations of the phospholipid matrix, clusters, and molecular species with insulin resistance were investigated. A significant association was confirmed between the phospholipid matrix and the homeostatic-model assessment of insulin resistance (HOMA-IR) by a distance-based linear model. Furthermore, three clustered phospholipid modules and 32 phospholipid molecular species were associated with HOMA-IR with the strict control of demographic and lifestyle parameters, family history of diabetes, BMI, WC, and blood lipid parameters. The overall decline in lysophosphatidylcholines (LPCs), the decrease in saturated lysophosphatidylethanolamines (LPEs), the decrease in polyunsaturated/plasmenyl phosphatidylcholines (PCs), and the increase in polyunsaturated phatidylethanolamines (PEs) were the prominent characters of plasma phospholipid perturbation associated with insulin resistance. This suggested that PC- and PE-related metabolic pathways were widely involved in the process of insulin resistance, especially the disorder of LPC acylation to diacyl-PC.

Objective To compare the application value of the likelihood ratio （LR） method and identity by state （IBS） method in the identification involving half sibling relationships， and to provide a reference for the setting of relevant standards for identification of half sibling relationship. Methods （1） Based on the same genetic marker combinations， the reliability of computer simulation method was verified by comparing the distributions of cumulated identity by state score （CIBS） and combined full sibling index in actual cases with the distributions in simulated cases. （2） In different numbers of three genetic marker combinations, the simulation of full sibling, half sibling and unrelated individual pairs, each 1 million pairs, was obtained; the CIBS, as well as the corresponding types of cumulative LR parameters， were calculated. （3） The application value of LR method was compared with that of IBS method， by comparing the best system efficiency provided by LR method and IBS method when genetic markers in different amounts and of different types and accuracy were applied to distinguish the above three relational individual pairs. （4） According to the existing simulation data， the minimum number of genetic markers required to distinguish half siblings from the other two relationships using different types of genetic markers was estimated by curve fitting. Results （1） After the rank sum test， under the premise that the real relationship and the genetic marker combination tested were the same， there was no significant difference between the simulation method and the results obtained in the actual case. （2） In most cases， under the same conditions， the system effectiveness obtained by LR method was greater than that by IBS method. （3） According to the existing data， the number of genetic markers required for full-half siblings and half sibling identification could be obtained by curve fitting when the system effectiveness reached 0.95 or 0.99. Conclusion When distinguishing half sibling from full sibling pairs or unrelated pairs， it is recommended to give preference to the LR method， and estimate the required number of markers according to the identification types and the population data， to ensure the identification effect.

Abstract Background Problem-based learning (PBL) is a widely adopted educational approach in medical education that aims to promote critical thinking and problem-solving in authentic learning situations. However, the impact of PBL educational mode on undergraduate medical students’ clinical thinking ability has been limitedly investigated. This study aimed to assess the influence of an integrated PBL curriculum on clinical thinking ability of medical students prior to clinical practice. Methods Two hundred and sixty-seven third-year undergraduate medical students at Nantong University were recruited in this study and were independently assigned to either the PBL or control group. The Chinese version of the Clinical Thinking Ability Evaluation Scale was used to assess clinical thinking ability, and the students’ performance in the PBL tutorials was assessed by tutors. All participants in both groups were required to complete the pre-test and post-test questionnaires to self-report their clinical thinking ability. A paired sample t-test, independent sample t-test and one-way analysis of variance test (ANOVA) were used to compare the difference in clinical thinking scores among different groups. Multiple linear regression was conducted to analyze the influencing factors correlated with clinical thinking ability. Results The clinical thinking ability of most third-year undergraduate medical students at Nantong University was at a high level. The PBL group had a higher proportion of students with high-level clinical thinking ability in the post-test compared to the control group. The pre-test scores of clinical thinking ability were similar between the PBL and control groups, but the post-test scores of clinical thinking ability in the PBL group were significantly higher than those in the control group. Additionally, there was a significant difference in clinical thinking ability between the pre-test and post-test in the PBL group. The post-test scores of sub-scales of critical thinking ability were significantly higher than the pre-test in the PBL group. Furthermore, the frequency of reading literature, time of PBL self-directed learning, and PBL performance score ranking were influencing factors on the clinical thinking ability of medical students in the PBL group. Moreover, there was a positive correlation between clinical thinking ability and the frequency of reading literature, as well as the scores of the PBL performance. Conclusions The integrated PBL curriculum model has an active impact on improving undergraduate medical students' clinical thinking ability. This improvement in clinical thinking ability may be correlated with the frequency of reading literature, as well as the performance of the PBL curriculum.

Abstract T lymphopenia, occurring in the early phase of sepsis in response to systemic inflammation, is commonly associated with morbidity and mortality of septic infections. We have previously shown that a sufficient number of T cells is required to constrain Toll-like receptors (TLRs) mediated hyperinflammation. However, the underlying mechanisms remains unsolved. Herein, we unveil that CD4+ T cells engage with MHC II of macrophages to downregulate TLR pro-inflammatory signaling. We show further that the direct contact between CD4 molecule of CD4+ T cells or the ectodomain of CD4 (soluble CD4, sCD4), and MHC II of resident macrophages is necessary and sufficient to prevent TLR4 overactivation in LPS and cecal ligation puncture (CLP) sepsis. sCD4 serum concentrations increase after the onset of LPS sepsis, suggesting its compensatory inhibitive effects on hyperinflammation. sCD4 engagement enables the cytoplasmic domain of MHC II to recruit and activate STING and SHP2, which inhibits IRAK1/Erk and TRAF6/NF-κB activation required for TLR4 inflammation. Furthermore, sCD4 subverts pro-inflammatory plasma membrane anchorage of TLR4 by disruption of MHC II-TLR4 raft domains that promotes MHC II endocytosis. Finally, sCD4/MHCII reversal signaling specifically interferes with TLR4 but not TNFR hyperinflammation, and independent of the inhibitive signaling of CD40 ligand of CD4+ cells on macrophages. Therefore, a sufficient amount of soluble CD4 protein can prevent excessive inflammatory activation of macrophages via alternation of MHC II-TLR signaling complex, that might benefit for a new paradigm of preventive treatment of sepsis.

Alzheimer’s disease (AD), an irreversible neurodegenerative disease that progressively impairs memory and cognitive judgment, severely affects the quality of life and imposes a heavy burden on the healthcare system. No cure is currently available for AD, in part because the pathogenesis of this disease has not been established. Animal models are essential for investigating AD pathogenesis and evaluating potential therapeutic strategies for AD. Some phenotypic and neuropathologic changes in AD patients can be recapitulated with genetic and pharmacologic approaches in animals. This article systematically reviews the animal models available for AD research, including transgenic, chemical- or drug-induced, and spontaneous animal models, and the characteristics of these animal models. In this review we also discuss the challenges and constraints when using AD animal models. Although no single animal model can reproduce all pathologic aspects and behavioral features in AD patients, the currently available AD models are valuable tools for deciphering the pathogenic mechanisms underlying AD and developing new anti-AD therapeutics.

Abstract Background Mantle cell lymphoma (MCL) is an uncommon heterogeneous subtype of B cell non‐Hodgkin lymphoma, and clinical features in MCL appear regional characteristics. MCL treatment opinions are not uniform between countries or regions within Asia and China, and Asian patient‐specific data for MCL treatment are fewer. The study aims to explore the clinical characteristics, treatment patterns and prognosis of MCL patients in China. Methods A total of 805 patients diagnosed with MCL between April 1999 and December 2019 at 19 comprehensive hospitals in China were included in this retrospective analysis. Kaplan‐Meier method coupled with the log‐rank test was used for univariate analysis, and COX proportional hazards model was used for multivariate analysis (MVA). p < 0.05 was consided statistically significant. All outputs were produced using R version 4.1.0. Results The median age of the cohort was 60.0 years with a male‐to‐female ratio of 3.36:1. Five‐year progression‐free survival (PFS) and overall survival (OS) rates were 30.9% and 65.0%, respectively. High‐intermediate/high‐risk group according to MIPI‐c, without high‐dose cytarabine, lack of Auto‐SCT as consolidation and maintenance treatment and SD/PD in initial treatment remained statistically relevant to poor PFS on MVA, and ki67 ≥50%, B symptoms, high‐intermediate/high risk group according to MIPI‐c, without high‐dose cytarabine, lack of maintenance treatment, SD/PD in initial treatment and relapse/refractory state were independently associated with poorer OS on MVA. Conclusions First‐line high dose cytarabine exposure, auto‐SCT as consolidation therapy obtained survival benefits in Chinese population. Our study further confirmed the value of maintenance treatment and explored the application of new drug treatment and bendamustine in R/R MCL patients.

AIM: To investigate the effect of all-trans retinoic acid (ATRA) on retinol dehydrogenase 5 (RDH5), matrix metalloproteinase-2 (MMP-2) and transforming growth factor-β2 (TGF-β2) transcription levels, and the effect of RDH5 on MMP-2 and TGF-β2 in retinal pigment epithelium (RPE) cells. METHODS: After adult RPE cell line-19 (ARPE-19 cells) intervened with gradient concentrations of ATRA (0-20 μmol/L) for 24h, flow cytometry was used to detect the proliferation and apoptosis of cells in each group, and quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect RDH5, MMP-2 and TGF-β2 mRNA expression. Then, after ARPE-19 cells transfected with three different siRNA targets for 48h, the RDH5 knockdown efficiency of each group and expression of MMP-2 and TGF-β2 mRNA within them was detected by qRT-PCR. RESULTS: Flow cytometry results showed that ATRA could inhibit the proliferation of RPE cells and promote the apoptosis of RPE cells, and the difference of apoptosis was statistically significant when the ATRA concentration exceeded 5 μmol/L and compared with the normal control group (P=0.027 and P=0.031, respectively). qRT-PCR results showed that ATRA could significantly inhibit the expression level of RDH5 mRNA (P

Objectives: From March to June 2021, the reported number of clinically diagnosed endemic typhus in Anhui and Hubei provinces of China nearly increased four-fold compared with the monthly average numbers in last 5 years. An etiological and epidemiological investigation was initiated. Methods: The clinical specimens from the reported patients and the potential vector ticks were collected for molecular and serological detection, as well as cell culturing assay to identify the potential pathogen. Results: Polymerase chain reaction and sequence analysis of rrs and groEL showed that the pathogen from these patients was Ehrlichia sp., isolated from Haemaphysalis longicornis attached to these patients. The phylogenetic analysis based on 39 Ehrlichia genomes suggested that it should be taxonomically classified as a novel species, tentatively named “Candidatus Ehrlichia erythraense”. A total of 19 of 106 cases were confirmed as Candidatus Ehrlichia erythraense infections by polymerase chain reaction, sequencing, and/or serological tests. The most frequent symptoms were fever (100%), rashes (100%), asthenia (100%), anorexia (100%), and myalgia (79%). Conclusion: The occurrence of the disease presenting with fever and rashes in Anhui and Hubei provinces was caused by a novel species of the genus Ehrlichia; physicians need to be aware of this newly-discovered pathogen to ensure appropriate testing, treatment, and regional surveillance.

AIM: To describe a novel suture approach for transscleral fixation of C-loop intraocular lenses (IOL) and to compare the surgical outcomes with the four-haptics posterior chamber (PC)-IOL technique. METHODS: We retrospectively analyzed 16 eyes of 16 patients who underwent transscleral fixation of C-loop PC-IOLs using a flapless one-knot suture technique, which were followed up for longer than 17mo. In this technique, the capsulorless IOL was suspended using a single suture for transscleral fixation of four feet. Then we compared its surgical outcomes and complications with the four-haptics PC-IOLs using the Student's t test and Chi-square test. RESULTS: Sixteen patients of 16 eyes with a mean age of 58.3±10.1y (42-76y) who received transscleral C-loop IOL implantation due to trauma, vitrectomy, or cataract surgery with inadequate capsule support showed improved visual acuity. The difference was not significant between two IOLs except the surgery time (P>0.05). The mean operation times of C-loop IOL surgery was 24.1±1.83min and 31.3±4.47min of the four-haptics PC-IOL method (P0.05). We did not detect any optic capture, IOL decentration or dislocation, suture exposed, or cystoid macular edema in patients underwent C-loop IOLs surgery. CONCLUSION: The novel flapless one-knot suture technique for transscleral fixation of C-loop IOL is a simple, reliable, and stable technique.

Abstract Background High-intensity chemotherapy regimens are often used in adult T-cell lymphoblastic lymphoma (T-LBL) patients. Nevertheless, the response rate remains unsatisfactory due to emergence of chemoresistance. Growing evidence has shown that long non-coding RNAs (lncRNAs) are involved in tumor progression and chemoresistance. Herein, we investigated the potential role of lncRNAs in T-LBLs. Methods RNAseq was used to screen and identify candidate lncRNAs associated with T-LBL progression and chemoresistance. Luciferase reporter assay was used to examine the binding of miR-371b-5p to the 3’UTR of Smad2 and LEF1, and the binding of TCF-4/LEF1 to the promoter of LINC00183. Chromatin immunoprecipitation assay was undertaken to analyze the connection between LEF1 and the LINC00183 promoter region. RNA immunoprecipitation assays were used to explore the mechanism whereby LINC00183 regulated miR-371b-5p. MTT and flow cytometry assays were used to measure apoptosis of T-LBL cells. Results LINC00183 was upregulated in T-LBL progression and chemoresistant tissues in both the Sun Yat-sen University Cancer Center dataset and the First Affiliated Hospital of Anhui Medical University dataset. High expression of LINC00183 was correlated with poorer overall survival and progression-free survival of T-LBL patients compared to those with low expression of LINC00183. Furthermore, miR-371b-5p was negatively regulated by LINC00183. In vivo and in vitro assays showed that LINC00183-mediated T-LBL chemoresistance depended on miR-371b-5p expression. The direct binding of miR-371b-5p to Smad2 and LEF1 was verified by luciferase assays. It was shown that TCF4/LEF1 could bind to the LINC00183 promoter site and increase its transcript level. Downregulation of miR-371b-5p led to increased expression of Smad2/LEF1, and in turn increased LINC00183 expression. Additionally, phospho-Smad2 promotes nuclear translocation of β-catenin, LINC00183 downregulation decreased chemoresistance induced by β-catenin and TGF-β1 in T-LBL cells. Conclusion We unraveled a β-catenin-LINC00183-miR-371b-5p-Smad2/LEF1 feedback loop that promotes T-LBL progression and chemoresistance, indicating that LINC00183 may serve as a potential therapeutic target in T-LBLs.

The therapeutic benefits of available FLT3 inhibitors for AML are limited by drug resistance, which is related to mutations, as well toxicity caused by off-target effects. In this study, we introduce a new small molecule FLT3 inhibitor called danatinib, which was designed to overcome the limitations of currently approved agents. Danatinib demonstrated greater potency and selectivity, resulting in cytotoxic activity specific to FLT3-ITD and/or FLT3-TKD mutated models. It also showed a superior kinome inhibition profile compared to several currently approved FLT3 inhibitors. In diverse FLT3-TKD models, danatinib exhibited substantially improved activity at clinically relevant doses, outperforming approved FLT3 inhibitors. In vivo safety evaluations performed on the granulopoiesis of transgenic myeloperoxidase (MPO) zebrafish and mice models proved danatinib to have an acceptable safety profile. Danatinib holds promise as a new and improved FLT3 inhibitor for the treatment of AML, offering long-lasting remissions and improved overall survival rates.

Stem cells have self-renewal, replication, and multidirectional differentiation potential, while progenitor cells are undifferentiated, pluripotent or specialized stem cells. Stem/progenitor cells secrete various factors, such as cytokines, exosomes, non-coding RNAs, and proteins, and have a wide range of applications in regenerative medicine. However, therapies based on stem cells and their secreted exosomes present limitations, such as insufficient source materials, mature differentiation, and low transplantation success rates, and methods addressing these problems are urgently required. Ultrasound is gaining increasing attention as an emerging technology. Low-intensity pulsed ultrasound (LIPUS) has mechanical, thermal, and cavitation effects and produces vibrational stimuli that can lead to a series of biochemical changes in organs, tissues, and cells, such as the release of extracellular bodies, cytokines, and other signals. These changes can alter the cellular microenvironment and affect biological behaviors, such as cell differentiation and proliferation. Here, we discuss the effects of LIPUS on the biological functions of stem/progenitor cells, exosomes, and non-coding RNAs, alterations involved in related pathways, various emerging applications, and future perspectives. We review the roles and mechanisms of LIPUS in stem/progenitor cells and exosomes with the aim of providing a deeper understanding of LIPUS and promoting research and development in this field.

Background: Previous studies have shown that F-53B exposure may be neurotoxic to animals, but there is a lack of epidemiological evidence, and its mechanism needs further investigation. Methods: Serum F-53B concentrations and Wisconsin Card Sorting Test (WCST) were evaluated in 314 growing children from Guangzhou, China, and the association between them were analyzed. To study the developmental neurotoxicity of F-53B, experiments on sucking mice exposed via placental transfer and breast milk was performed. Maternal mice were orally exposed to 4, 40, and 400 μg/L of F-53B from postnatal day 0 (GD0) to postnatal day 21 (PND 21). Several genes and proteins related to neurodevelopment, dopamine anabolism, and synaptic plasticity were examined by qPCR and western blot, respectively, while dopamine contents were detected by ELISA kit in weaning mice. Results: The result showed that F-53B was positively associated with poor WCST performance. For example, with an interquartile range increase in F-53B, the change with 95 % confidence interval (CI) of correct response (CR), and non-perseverative errors (NPE) was −2.47 (95 % CI: −3.89, −1.05, P = 0.001), 2.78 (95 % CI: 0.79, 4.76, P = 0.007), respectively. Compared with the control group, the highest exposure group of weaning mice had a longer escape latency (35.24 s vs. 51.18 s, P = 0.034) and a lesser distance movement (34.81 % vs. 21.02 %, P

Abstract Developing smart room‐temperature phosphorescence (RTP) materials with facile and efficient strategies have attracted increasing attention. Herein, tunable RTP materials with two phosphorescent sources and stepwise enhanced phosphorescence in water are obtained through an in‐situ self‐assembly strategy based on the sensitization of phosphors by trimesic acid (TMA) through simple doping and the rigidification of phosphors by hydrogen‐bonded organic frameworks (HOFs). As expected, doped TMA+phosphors simultaneously promote the RTP emission of phosphors and maintain TMA phosphorescence. In‐situ assembled HOF(MA‐TMA)@phosphors facilitate smart RTP emission in water due to the coexistence of phosphorescent HOF(MA‐TMA) host and phosphors guest. Additionally, such RTP materials with good processability demonstrate the application potential in information security, benefitting from their varied afterglow lifetimes and easy luminous recognition in the darkness. This work will inspire the design of dual phosphorescent source RTP systems and provide new strategies for the development of smart RTP materials in water.