Identification of transcription factor BnHDG4-A08 as a novel candidate associated with the accumulation of oleic, linoleic, linolenic, and erucic acid in Brassica napus.

KEY MESSAGE: We screened 47 significantly associated haplotype blocks for oleic, linoleic, linolenic, and erucic acid, with 17 blocks influencing multiple traits. A novel candidate of transcription factor BnHDG4 A08 influencing oleic, linoleic, linolenic, and erucic acid was identified, by a joint strategy of haplotype-based genome-wide association study, genomic resequencing, gene cloning, and co-expression network Fatty acid (FA) composition determines the quality and economic value of rapeseed oil (Brassica napus). However, the molecular network of FAs is unclear. In the current study, multi-strategies of haplotype-based genome-wide association study (GWAS), genomic resequencing, gene cloning, and co-expression network were joint to reveal novel genetic factors influencing FA accumulation in rapeseed. We identified 47 significantly associated haplotype blocks for oleic, linoleic, linolenic, and erucic acid, with 17 blocks influencing multiple traits, using a haplotype-based GWAS with phenotype data from 203 Chinese semi-winter accessions. A total of 61 rapeseed orthologs involved in acyl-lipid metabolism, carbohydrate metabolism, or photosynthesis were identified in these 17 blocks. Among these genes, BnHDG4-A08, encoding a class IV homeodomain leucine-zipper transcription factor, exhibited two single-nucleotide polymorphisms (SNPs) in the exon and intron, with significant associations with oleic, linoleic, linolenic, and erucic acid. Gene cloning further validated two SNPs in the exon of BnHDG4-A08 in a population with 75 accessions, leading to two amino acid changes (T372A and P366L) and significant variation of oleic, linoleic, linolenic, and erucic acid. A competitive allele-specific PCR (KASP) marker based on the SNPs was successfully developed and validated. Moreover, 98 genes exhibiting direct interconnections and high weight values with BnHDG4-A08 were identified through co-expression network analysis using transcriptome data from 13 accessions. Our study identified a novel FA candidate of transcription factor BnHDG4-A08 influencing oleic, linoleic, linolenic, and erucic acid. This gene provides a potential promising gene resource for the novel mechanistic understanding of transcription factors regulating FA accumulation.

Xantolisweimingii (Sapotaceae), a new species from the Yuanjiang River basin, Yunnan, southwest China.

Xantolisweimingii sp. nov. (Sapotaceae) is described and illustrated from Yunnan, southwest China. The new species is morphologically most similar to X.tomentosa (Roxb.) Raf., but differs from the latter in the ovate or obovate leaves, entirely glabrous corollas, lanceolate, ca. 5 mm long staminodes, fringed at the base. We provided a distribution map and a preliminary conservation assessment for the new species. Additionally, an updated dichotomous key to all known species of Xantolis is presented.

Identification of a pathogenic variant and pre-implantation genetic testing for a Chinese family affected with split-hand/foot malformation.

Split-hand/foot malformation is a serious congenital limb malformation characterized by syndactyly and underdevelopment of the phalanges and metatarsals. In this study, we reported a case of a fetus with hand-foot cleft deformity. Whole exome and Sanger sequencing were used to filter out candidate gene mutation sites and provide pre-implantation genetic testing(PGT) for family members. Genetic testing results showed that there was a homozygous mutation c.786G>A (p.Trp262*) in the fetal WNT10B, and both parents were carriers of heterozygous mutations. PGT results showed that out of the two blastocysts, one was a heterozygous mutant and the other was a homozygous mutant. All the embryos had diploid chromosomes. The heterozygous embryo was transferred, and a singleton pregnancy was successfully achieved. This study suggests that homozygous mutations in WNT10B are the likely cause of hand-foot clefts in this family. For families with monogenic diseases, preimplantation genetic testing can effectively prevent the birth of an affected child only after identifying the pathogenic mutation.

Shenqi Pill alleviates acetaminophen-induced liver injury: a comprehensive strategy of network pharmacology and spectrum-effect relationship reveals mechanisms and active components.

BACKGROUND: Acetaminophen (APAP), commonly used for its antipyretic and analgesic properties, can cause severe liver injury or even acute liver failure when overdosed. However, the options for treating APAP-induced liver toxicity are limited. Shenqi Pill (SQP), a traditional Chinese herbal formula, has shown effectiveness in treating various liver ailments. SQP consists of cinnamon, aconite, rehmannia, cornus, peony bark, Chinese yam, poria, and alisma in a ratio of 1:1:8:4:3:4:3:3. However, the mechanisms and active components of SQP that counteract drug-induced liver injury (DILI) are not well understood. PURPOSE: This study aimed to explore the protective effects of SQP against APAP-induced liver injury in both laboratory and animal settings. It seeks to identify the active components and potential mechanisms by which SQP targets mitochondria to alleviate liver damage. METHODS: A mouse model with APAP-induced liver injury was established to assess SQP's therapeutic impact. This study then analyzed the components of SQP using UPLC-Q-TOF-MS in both in vivo and in vitro environments. Network pharmacology and the GEO database helped predict potential pathways and targets. Potential active components were identified through spectrum-effect relationship analysis and validated their efficacy using Seahorse assays and molecular docking. RESULTS: Treatment with SQP significantly reduced liver dysfunction, tissue damage, lipid metabolic disruptions, and inflammation caused by APAP in mice. In cellular tests, SQP-treated serum notably enhanced mitochondrial function, maintained membrane potential, decreased ROS levels, and prevented mitochondrial permeability transition pore opening. Biochemically, SQP reversed the suppression of p-AMPK, p-ACC, CPT1, and ACADM expression caused by APAP overdose. This study identified 97 in vitro and 24 in vivo components of SQP, with eight showing significant mitochondrial benefits. Molecular docking studies suggest that fuziline and paeoniflorin could activate AMPK. CONCLUSION: SQP effectively mitigates APAP-induced liver injury by enhancing mitochondrial function via the AMPK-ACC-CPT1-ACADM pathway. Moreover, this study introduces a novel strategy for analyzing the relationship between the chemical and pharmacological properties of drug-containing serum, successfully identifying compounds with mitochondrial activity. Fuziline and paeoniflorin, in particular, emerge as promising mitochondrial protectants and warrant further investigation. This research underpins the development of innovative treatments for DILI using SQP and its components.

Case report: Clinicopathological characteristic of two cases of primary endometrial squamous cell carcinoma and review of the literature.

Primary endometrial squamous cell carcinoma (PESCC) is a rare malignant tumor. To investigate the clinical and pathological features of PESCC, two cases of PESCC in Fujian Maternal and Child Health Hospital were retrospectively studied and the literatures were reviewed. Both of the two cases were menopausal women aged 57-62 years, clinically presenting with "vaginal discharge". Case 1 was a non-keratinising squamous cell carcinoma with high-risk HPV infection. Tumor infiltrated in deep myometrium with multifocal intravascular thrombus and macro metastases to one pelvic lymph node (1/15) and abdominal aortic lymph node (1/1). Lung metastasis occurred 36 months after the surgery. After surgical resection and without postoperative supplemental therapy, the patient remained tumor-free for 110 months to date. Case 2 had a history of breast cancer for 5 years and long-term intake of aromatase inhibitor drugs without HPV infection. It was a keratinized squamous cell carcinoma. Tumor also infiltrated in deep myometrium with multifocal intravascular thrombus and one pelvic lymph node metastasis (1/18), However, no metastasis was seen elsewhere. To date, the patient survived for 16 months without tumor after surgery. Both of the two cases expressed squamous epithelial markers P40, P63, and CK5/6, but neither expressed PAX8 or PR. Case 1 had diffuse expression of P16, wild-type P53, and ER-negative. Case 2 had negative P16, mutant P53, and focal positive ER. PESCC is often associated with HPV infection and low estrogen levels. However, studies in the literatures have found that P16 expression is not always consistent with HPV infection, indicating that PESCC cannot be easily classified as HPV-associated or non-dependent like cervical cancer. There are two main patterns of P16 and P53 expression, P16-positive/P53 wild-type and P16-negative/P53-mutant, but no positive expression of both has been seen so far. It is worth noting that we reported the second case of PESCC with a history of breast cancer, where the patient had been taking the oral aromatase inhibitor drug (exemestane) for a long period of time to reduce the estrogen level, indicating the low estrogen level may be also a key factor in the pathogenesis of PESCC.

Effects of preoperative valgus deformity in patients undergoing neutrally aligned total knee arthroplasty: A retrospective cohort study with a minimum five-year follow-up.

OBJECTIVES: This study aimed to investigate the relationship between the severity of preoperative valgus deformity and clinical outcomes of neutrally aligned total knee arthroplasty (TKA). PATIENTS AND METHODS: A total of 376 knees with valgus deformity who underwent TKA from January 2006 to March 2014 were retrospectively screened, and 287 knees (242 patients; 32 males, 210 females; mean age: 64.5±8.8 years; range, 35 to 83 years) aligned neutrally after the operation were included. Patients were divided into four groups based on the preoperative hip-knee-ankle (HKA): mild (0°< HKA ≤5°, n=94), moderate (5°< HKA ≤10°, n=74), severe (10°< HKA ≤15°, n=75), and very severe (HKA >15°, n=44) groups. Range of motion (ROM), Knee Society Score (KSS), Visual Analog Scale (VAS) dynamic pain scores, and Forgotten Joint Score (FJS) were evaluated. Mechanical failures were recorded to assess prosthesis survival. A survival rate analysis was performed using Kaplan-Meier survival analysis. RESULTS: The degree of preoperative valgus deformity did not have a significant impact on the postoperative ROM, KSS, VAS dynamic pain scores, or FJS at the last follow-up. There were no significant differences in cumulative survival rates of neutrally aligned TKAs at 10 years between the four groups (p=0.513). CONCLUSION: The severity of preoperative valgus deformity did not affect the clinical outcomes of neutrally aligned TKAs in the minimum five-year follow-up. Additionally, it did not impact the survival rates of neutrally aligned TKAs over 10 years.

Comparison of the Accuracy of HSV1 and HSV2 Antibody Tests with PCR in the Diagnosis of Recurrent Genital Herpes.

Objective: To assess the accuracy of HSV1and HSV2 antibody testing in identifying genital herpes infection. Methods: A cohort of 299 patients previously diagnosed with recurrent genital herpes, confirmed via PCR, were tested using ELISA for HSV1 and HSV2 IgM and IgG antibodies. The study compared the accuracy of HSV1 and HSV2 antibody tests in diagnosing genital herpes. Results: Among 299 patients, 14 tested positives for HSV1 DNA. Of these, 9 had HSV1 IgG antibodies, but none had HSV2 IgG antibody. Among 278 patients with HSV2 DNA, 149 had HSV1 IgG, 9 had HSV2 IgG, and 97 had both. Seven patients had both HSV1 and HSV2 DNA; 3 had HSV1 IgG, 1 had HSV2 IgG, and 3 had both. The accuracy of HSV1 IgG for HSV1 infection was 64.2%, and for HSV1 and HSV2 co-infection, 85.7%. The accuracy of HSV2 IgG for HSV2 infection was 38.1%, and for HSV1 and HSV2 co-infection, 57.1%. The combined antibody positivity accuracy was 34.9%. Conclusion: Genital herpes is primarily caused by HSV2 (92.98%). A smaller percentage is HSV1 (4.67%) or co-infection (2.34%). Despite relatively low diagnostic accuracy (34.9-85.7%) for antibody detection, combined antibody testing is necessary. Herpes DNA testing is recommended for accurate diagnosis. Absence of antibodies does not rule out genital herpes and clinical assessment is essential.

Pembrolizumab plus enzalutamide for metastatic castration-resistant prostate cancer progressing on enzalutamide: cohorts 4 and 5 of the phase 2 KEYNOTE-199 study.

BACKGROUND: KEYNOTE-199 (NCT02787005) is a multicohort phase 2 study evaluating pembrolizumab in patients with metastatic castration-resistant prostate cancer (mCRPC). Results from cohorts 4 (C4) and 5 (C5) are presented. METHODS: Eligible patients had not received chemotherapy for mCRPC and had responded to enzalutamide prior to developing resistance as defined by Prostate Cancer Clinical Trials Working Group 3 guidelines. Patients with RECIST-measurable disease were enrolled in C4, and patients with bone-only or bone-predominant disease were enrolled in C5. All patients received pembrolizumab 200 mg every 3 weeks for ≤35 cycles with ongoing enzalutamide until progression, unacceptable toxicity, or withdrawal. The primary end point was objective response rate (ORR) per RECIST v1.1 by blinded independent central review in C4. Secondary end points included disease control rate (DCR), overall survival, and safety in each cohort and both cohorts combined. RESULTS: A total of 126 patients were treated (C4, n = 81; C5, n = 45). Median age was 72 years (range 43-92), and 87.3% had received ≥6 months of enzalutamide prior to study entry. Confirmed ORR was 12.3% (95% CI 6.1-21.5%) for C4. Median duration of response in C4 was 8.1 months (range, 2.5+ to 15.2), and 5 of these patients experienced an objective response lasting ≥6 months. DCR was 53.1% (95% CI 41.7-64.3%) in C4 and 51.1% (95% CI 35.8-66.3%) in C5. Median overall survival was 17.6 months (95% CI 14.0-22.6) in C4 and 20.8 months (95% CI 14.1-28.9) in C5. Grade ≥3 treatment-related adverse events occurred in 35 patients (27.8%); 2 patients in C4 died from immune-related adverse events (myasthenic syndrome and Guillain-Barré syndrome). CONCLUSIONS: The addition of pembrolizumab to ongoing enzalutamide treatment in patients with mCRPC that progressed on enzalutamide after initial response demonstrated modest antitumor activity with a manageable safety profile. CLINICAL TRIAL REGISTRY AND ID: ClinicalTrials.gov, NCT02787005.

Comparison of ranibizumab and conbercept treatment in type 1 prethreshold retinopathy of prematurity in zone II.

PURPOSE: The treatment with anti-VEGF for Retinopathy of prematurity (ROP) has already been widely applied in clinics even though there are still many concerns about this treatment. In this project we investigated the clinical outcomes of intra-vitreous conbercept (IVC) and ranibizumab (IVR) injection for treating type 1 prethreshold ROP in Zone II. METHODS: The data of ROP infants receiving IVR or IVC from January 2017 to March 2020 who were followed up for at least 12 months in our hospital was studied in the present retrospective study. Regression, reactivation, complications, and ocular biological parameters were evaluated. RESULTS: One hundred twenty-five eyes (64 infants) in IVC group and 229 eyes (117 infants) in IVR group were observed in the study. All infants showed good response to the two anti-VEGF agents. No eyes deteriorated during the observation. No significant difference was found between the two groups as to the regression within one week and one month, the reactivation rate, and the retreatment interval (p > 0.05) whereas retinal complete vascularization rate at 6 mons after the initial treatment and mean completion time of retinal vascularization after initial injection showed significant difference (p < 0.05). At 12 mons PMA the ocular parameters also presented no statistical difference between the two treated groups (p > 0.05). However, the ocular showed slight myopic tendency with the anti-VEGF treatment when compared to the control group (p < 0.05) whereas there was no statistical difference revealed between the two treated groups (p > 0.05). CONCLUSIONS: Both conbercept and ranibizumab for treating type 1 prethreshold ROP in Zone II are safe and effective. They had little effect on the development of ocular whereas there was a slight tendency of myopia after the treatment.

An integrated network pharmacology approach reveals that Ampelopsis grossedentata improves alcoholic liver disease via TLR4/NF-κB/MLKL pathway.

BACKGROUND: Alcohol-related liver damage is the most prevalent chronic liver disease, which creates a heavy public health burden worldwide. The leaves of Ampelopsis grossedentata have been considered a popular tea and traditional herbal medicine in China for more than one thousand years, and possess anti-inflammatory, antioxidative, hepatoprotective, and antiviral activities. PURPOSE: We explored the protective effects of Ampelopsis grossedentata extract (AGE) against chronic alcohol-induced hepatic injury (alcoholic liver disease, ALD), aiming to elucidate its underlying mechanisms. METHODS: Firstly, UPLC-Q/TOF-MS analysis and network pharmacology were used to identify the constituents and elucidate the potential mechanisms of AGE against ALD. Secondly, C57BL/6 mice were pair-fed the Lieber-DeCarli diet containing either isocaloric maltodextrin or ethanol, AGE (150 and 300 mg/kg/d) and silymarin (200 mg/kg) were administered to chronic ethanol-fed mice for 7 weeks to evaluate the hepatoprotective effects. Serum biochemical parameters were determined, hepatic and ileum sections were used for histologic examination, and levels of inflammatory cytokines and oxidative stress in the liver were examined. The potential molecular mechanisms of AGE in improving ALD were demonstrated by RNA-seq, Western blotting analysis, and immunofluorescence staining. RESULTS: Ten main constituents of AGE were identified using UPLC-Q/TOF-MS and 274 potential ALD-related targets were identified. The enriched KEGG pathways included Toll-like receptor signaling pathway, NF-κB signaling pathway, and necroptosis. Moreover, in vivo experimental studies demonstrated that AGE significantly reduced serum aminotransferase levels and improved pathological abnormalities after chronic ethanol intake. Meanwhile, AGE improved ALD in mice by down-regulating oxidative stress and inflammatory cytokines. Furthermore, AGE notably repaired damaged intestinal epithelial barrier and suppressed the production of gut-derived lipopolysaccharide by elevating intestinal tight junction protein expression. Subsequent RNA-seq and experimental validation indicated that AGE inhibited NF-κB nuclear translocation, suppressed IκB-α, RIPK3 and MLKL phosphorylation and alleviated hepatic necroptosis in mice. CONCLUSION: In this study, we have demonstrated for the first time that AGE protects against alcoholic liver disease by regulating the gut-liver axis and inhibiting the TLR4/NF-κB/MLKL-mediated necroptosis pathway. Therefore, our present work provides important experimental evidence for AGE as a promising candidate for protection against ALD.

[Mechanism of Modified Huoluo Xiaoling Pills against colorectal cancer based on network pharmacology, molecular docking, and experimental validation].

This study aims to predict the possible targets and related signaling pathways of Modified Huoluo Xiaoling Pills against colorectal cancer(CRC) by both network pharmacology and molecular docking and verify the mechanism of action by experiments. TCMSP was used to obtain the active ingredients and targets of Modified Huoluo Xiaoling Pills, and GeneCards, DrugBank, OMIM, and TTD were employed to acquire CRC-related targets. Cytoscape software was utilized to construct the drug-active ingredient-target network, and the STRING database was applied to establish the protein-protein interaction(PPI) network. DAVID platform was adopted to investigate the targets in terms of GO function and KEGG pathway enrichment analysis. Molecular docking was performed in AutoDock Vina. HCT 116 cells were intervened by different concentrations of Modified Huoluo Xiaoling Pills-containing serum, and CCK-8 was used to detect the proliferation inhibition of HCT 116 cells in each group. Transwell was employed to show the invasive abi-lity of HCT 116 cells, and Western blot was taken to reveal the expression levels of ß-catenin, cyclinD1, c-Myc, as well as epithelial-mesenchymal transition(EMT) marker proteins E-cadherin, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST in HCT 116 cells. The network pharmacological analysis yielded 242 active ingredients of Modified Huoluo Xiaoling Pills, 1 844 CRC targets, and 127 overlapping targets of CRC and Modified Huoluo Xiaoling Pills, and the signaling pathways related to CRC involved PI3K-Akt, TNF, HIF-1, IL-17, Wnt, etc. Molecular docking showed that the key active ingredients had a stable binding conformation with the core proteins. CCK-8 indicated that Modified Huoluo Xiaoling Pills significantly inhibited the proliferation of HCT 116 cells. Transwell assay showed that with increasing concentration of Modified Huoluo Xiaoling Pills containing serum, the invasive ability of HCT 116 cells was more obviously inhibited. The expression of ß-catenin, cyclinD1, c-Myc, N-cadherin, vimentin, MMP2, MMP7, MMP9, and TWIST proteins were suppressed, and the expression of E-cadherin was improved by the intervention of drug-containing serum. Thus, it can be seen that Modified Huoluo Xiaoling Pills restrains the proliferation, invasion, and metastasis of CRC cells through multiple components, multiple targets, and multiple pathways, and the mechanism of action may be related to the inhibition of the activation of the Wnt/ß-catenin signaling pathway, thereby affecting the occurrence of EMT.

Psoralen attenuates cigarette smoke extract-induced inflammation by modulating CD8+ T lymphocyte recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Chronic obstructive pulmonary disease (COPD) is a respiratory inflammatory disease. Psoralen (PSO) is the main pharmacological component identified from Bu-Shen-Fang-Chuan formula which has been traditionally used in treatment of COPD, yet its efficacy in COPD inflammation were unreported. In this study, we aimed to elucidate the anti-inflammatory potential of PSO in COPD and unravel the underlying mechanisms, focusing on T lymphocyte recruitment and the modulation of chemokines, namely monokine induced by interferon-gamma (CXCL9), interferon inducible protein 10 (CXCL10), and interferon inducible T-Cell alpha chemoattractant (CXCL11). In vitro, RAW264.7 was stimulated by interferon (IFN)-γ + cigarette smoke extract (CSE) and were treated with PSO (2.5, 5, 10 µM), then the levels of chemokines and the activation of Janus kinase (JAK)/Signal transducer and activator of transcription 1 (STAT1) pathway were analyzed by real time PCR and western blot. In vivo, a murine model was established by intraperitoneal injection of CSE on day 1, 8, 15, and 22, then treated with PSO (10 mg/kg). Our experiments in vitro illustrated that PSO reduced the levels of CXCL9, CXCL10, and CXCL11, and decreased the protein phosphorylation levels of JAK2 and STAT1. Additionally, PSO effectively improved inflammatory infiltration and decreased the proportion of CD8+ T cells in CSE-exposed mice. Furthermore, PSO reduced the levels of CXCL9, CXCL10, and CXCL11 in bronchoalveolar lavage fluid (BALF) and lung tissue, and decreased the protein phosphorylation levels of JAK2 and STAT1. In conclusion, our results revealed the therapeutic potential of PSO for COPD inflammation, possibly mediated through the regulation of CD8+ T cell recruitment and chemokines via the JAK2/STAT1 signaling pathway.

Role of ginsenoside Rb1 in attenuating depression-like symptoms through astrocytic and microglial complement C3 pathway.

Ginsenoside Rb1, known as gypenoside III, exerts antidepressant-like effects in previous studies. It has also been indicated that ginsenoside Rb1 regulated neuroinflammation via inhibiting NF-κB signaling. According to the evidence that astrocytes can regulate microglia and neuroinflammation by secreting complement C3, the present study aimed to demonstrate the molecular mechanisms underlying ginsenoside Rb1-induced antidepressant-like effects from the astrocytic and microglial complement C3 pathway. The complement C3 mediated mechanism of ginsenoside Rb1 was investigated in mice exposed to chronic restraint stress (CRS). The results showed that ginsenoside Rb1 reversed the depressive-like behaviors in CRS. Treatment with ginsenoside Rb1 reduced both the number of astrocytes and microglia. In addition, ginsenoside Rb1 suppressed TLR4/NF-κB/C3 signaling in the astrocytes of the hippocampus. Furthermore, ginsenoside Rb1 attenuated the contents of synaptic protein including synaptophysin and PSD95 in microglia, suggesting the inhibition of microglia-mediated synaptic elimination caused by CRS. Importantly, ginsenoside Rb1 also maintained the dendritic spines in mice. In conclusion, our results demonstrate that ginsenoside Rb1 produces the antidepressant-like effects by inhibiting astrocyte TLR4/NF-κB/C3 signaling to covert microglia from a pro-inflammatory phenotype (amoeboid) towards an anti-inflammatory phenotype (ramified), which inhibit the synaptic pruning in the hippocampus.

Assessing green production efficiency and spatial characteristics of China's real estate industry based on the undesirable super-SBM model.

As China strives to balance rapid urbanization with environmental conservation, increasing attention is being paid to the pursuit of green production efficiency (GPE) in the real estate industry. The undesirable super-SBM model was used to calculate the GPE of China's real estate industry from 2001 to 2020. Additionally, GPE spatial distribution characteristics in China's real estate industry were analyzed using the standard deviation ellipse (SDE), Moran's index, Theil index, random kernel density estimation (RKDA), and spatial Markov chain (SMC) methods. The GPE exhibited a U-shaped trend, with 2008 as the inflection point, first decreasing and then increasing. It reached a maximum value of 0.747 in 2020. The Theil index increased from 0.043 to 0.121 nationwide, indicating the overall characteristics of low-level slow growth, and imbalance. Discrepancies in input-output scales, the southward shift of economic centers, and population movements contribute significantly to the disparities between the east and west, north and south, and regions divided by the Hu Huanyong Line (Hu Line). The GPE exhibited club convergence characteristics; however, polarization phenomena exist in local areas. Spatial spillover effects were also observed in GPE. Finally, we provide recommendations for promoting green development in the real estate industry, including green building technology, fiscal subsidy investment, and population migration management.

Smartphone-assisted portable swabs for blood glucose management: A point-of-use assay for dual-mode visual detection based on bifunctional carbon dots.

Controlling glucose (Glu) intake is a "required course" for diabetics, thus quickly and precisely measuring the amount of Glu in food is crucial. For this purpose, a novel smartphone-assisted portable swab for the dual-mode visual detection of Glu was constructed combined the selectivity of natural enzymes with the controllable catalytic activity of nanozymes. Glu was specifically decomposed by glucose oxidase (natural enzyme) to produce H2O2, which was catalyzed by carbon dots (FeMn/N-CDs, nanozyme) to accelerate the reaction of o-phenylenediamine (OPD, colorless) to produce 2,3-diaminophenazine (DAP, yellow). As a result, the absorbance at 450 nm gradually increased with the increasing concentration of Glu, leading to a color change in the system from colorless to yellow. Meanwhile, the fluorescence of FeMn/N-CDs gradually decreased at 450 nm, while the fluorescence of DAP gradually increased at 550 nm, allowing for both ratiometric fluorescence and colorimetric dual-mode detection. Furthermore, natural enzyme and nanozyme together with OPD were co-loaded on the swabs to achieve cascade catalysis of Glu. The assembled portable swabs have detection ranges of 1-600 µM (LOD = 0.37 µM) and 4-1200 µM (LOD = 1.19 µM) for the colorimetric and fluorometric detection, respectively. The field test results on real samples demonstrated that the portable swabs have great promise for use in efficiently and accurately guiding the dietary intake of diabetics.

Association between metabolic dysfunction-associated steatotic liver disease and risk of colorectal cancer or colorectal adenoma: an updated meta-analysis of cohort studies.

Background and aims: In recent years, the relationship between metabolic dysfunction-associated steatotic liver disease (MASLD) and colorectal cancer (CRC) or colorectal adenoma (CRA) has gained widespread attention. Previous meta-analyses on this subject either incorporated numerous cross-sectional studies, which were susceptible to bias, or concentrated solely on a restricted number of cohort studies. Moreover, with the release of a substantial number of high-quality cohort studies on this subject in the past two years, the findings continue to be debated and contradictory. Therefore, we conducted an updated systematic review and meta-analysis of cohort studies to quantitatively evaluate the magnitude of the association between them. Methods: Comprehensive searches of PubMed, Web of Science, and Embase were conducted without language restrictions from the time of their creation up to December, 2023. The pooled hazard ratios (HRs) with 95% confidence interval (CIs) were calculated by the generic inverse variance based on the random-effects model. Moreover, subgroup and sensitivity analyses were performed. Results: A total of 15 cohort studies were analyzed in this meta-analysis, which included 9,958,412 participants. The meta-analysis of 13 cohort studies showed that MASLD was linked to a higher risk of CRC (HR=1.25, 95% CI: 1.15-1.36, P < 0.00001). Additionally, further subgroup analysis indicated that the combined HR remained consistent regardless of the study location, nomenclature of fatty liver disease (FLD), confirmation methods for FLD, sample size, follow-up time, and study quality. Furthermore, the meta-analysis of four cohort studies demonstrated that MASLD was correlated with an increased risk of CRA (HR=1.38, 95% CI: 1.17-1.64, P = 0.0002). The sensitivity analysis results further validated the robustness of the aboved findings. Conclusion: The results of our meta-analysis indicated that MASLD was associated with an increased risk of incident CRC/CRA. In the future, it is necessary to conduct more prospective cohort studies to thoroughly assess potential confounding factors, particularly in individuals from Europe and North America. Furthermore, related mechanism studies should be conducted to enhance our understanding of the link between MASLD and CRC/CRA. Systematic review registration: Open Science Framework registries (https://osf.io/m3p9k).

Intrinsic Self-Healable, Corrosion-Resistant Silicone Coating Based on Quadruple Hydrogen-Bonded Supramolecular Polymer.

Corrosion-resistant coatings with self-healing capabilities are still a great challenge for metal protection. In this study, a corrosion-resistant coating with intrinsic self-healing capabilities was developed by compounding hydroxy-terminated silicone oil (HTSO) with 2-ureido-4[1H]-pyrimidone (UPy) derivatives. The smooth surface of the coating was shown by scanning electron microscopy (SEM), and good smoothness was also exhibited in the cross-section, which indicated that the coating is very homogeneous from the top to the bottom. Thermogravimetric analysis (TG) was employed to illustrate the temperature-resistant characteristics of the coating, revealing its significant chemical stability up to 360 °C. The corrosion resistance of the coating is assessed through electrochemical impedance spectroscopy (EIS), the typical impedance at 0.01 Hz is 1.70 × 109 and 2.44 × 108 Ω·cm2 before and after exposure to a 3.5 wt % NaCl solution for 70 days. There was no significant change in the water contact angle of the coatings before and after immersion; however, the adhesion strength was reduced. Notably, the coating demonstrates immediate and multiple self-healing properties. The tensile stress of the associated healing sample experiences an augmentation within the temperature range of 30-120 °C, with the critical fracture strain of the healed sample reaching 235% at 120 °C. The self-healing mechanism of the coating is systematically investigated using in situ Raman spectroscopy.

Adaptive evolution of antioxidase-related genes in hypoxia-tolerant mammals.

To cope with the damage from oxidative stress caused by hypoxia, mammals have evolved a series of physiological and biochemical traits, including antioxidant ability. Although numerous research studies about the mechanisms of hypoxia evolution have been reported, the molecular mechanisms of antioxidase-related genes in mammals living in different environments are yet to be completely understood. In this study, we constructed a dataset comprising 7 antioxidase-related genes (CAT, SOD1, SOD2, SOD3, GPX1, GPX2, and GPX3) from 43 mammalian species to implement evolutionary analysis. The results showed that six genes (CAT, SOD1, SOD2, SOD3, GPX1, and GPX3) have undergone divergent evolution based on the free-ratio (M1) model. Furthermore, multi-ratio model analyses uncovered the divergent evolution between hypoxic and non-hypoxic lineages, as well as various hypoxic lineages. In addition, the branch-site model identified 9 positively selected branches in 6 genes (CAT, SOD1, SOD2, SOD3, GPX2, and GPX3) that contained 35 positively selected sites, among which 31 positively selected sites were identified in hypoxia-tolerant branches, accounting for 89% of the total number of positively selected sites. Interestingly, 65 parallel/convergent sites were identified in the 7 genes. In summary, antioxidase-related genes are subjected to different selective pressures among hypoxia-tolerant species living in different habitats. This study provides a valuable insight into the molecular evolution of antioxidase-related genes in hypoxia evolution in mammals.

Catechin Protects against Lipopolysaccharide-induced Depressive-like Behaviour in Mice by Regulating Neuronal and Inflammatory Genes.

BACKGROUND: Many studies have suggested that tea has antidepressant effects; however, the underlying mechanism is not fully studied. As the main anti-inflammatory polyphenol in tea, catechin may contribute to the protective role of tea against depression. OBJECTIVE: The objective of this study is to prove that catechin can protect against lipopolysaccharide (LPS)-induced depressive-like behaviours in mice, and then explore the underlying molecular mechanisms. METHODS: Thirty-one C57BL/6J mice were categorized into the normal saline (NS) group, LPS group, catechin group, and amitriptyline group according to their treatments. Elevated Plus Maze (EPM), Tail Suspension Test (TST), and Open Field Test (OFT) were employed to assess depressive- like behaviours in mice. RNA sequencing (RNA-seq) and subsequent Bioinformatics analyses, such as differential gene analysis and functional enrichment, were performed on the four mouse groups. RESULTS: In TST, the mice in the LPS group exhibited significantly longer immobility time than those in the other three groups, while the immobility times for the other three groups were not significantly different. Similarly in EPM, LPS-treated mice exhibited a significantly lower percentage in the time/path of entering open arms than the mice in the other three groups, while the percentages of the mice in the other three groups were not significantly different. In OFT, LPS-treated mice exhibited significantly lower percentages in the time/path of entering the centre area than those in the other three groups. The results suggested that the LPS-induced depression models were established successfully and catechin can reverse (LPS)-induced depressive-like behaviours in mice. Finally, RNA-seq analyses revealed 57 differential expressed genes (DEGs) between LPS and NS with 19 up-regulated and 38 down-regulated. Among them, 13 genes were overlapped with the DEGs between LPS and cetechin (in opposite directions), with an overlapping p-value < 0.001. The 13 genes included Rnu7, Lcn2, C4b, Saa3, Pglyrp1, Gpx3, Lyz2, S100a8, S100a9, Tmem254b, Gm14288, Hbb-bt, and Tmem254c, which might play key roles in the protection of catechin against LPS-induced depressive-like behaviours in mice. The 13 genes were significantly enriched in defense response and inflammatory response, indicating that catechin might work through counteracting changes in the immune system induced by LPS. CONCLUSION: Catechin can protect mice from LPS-induced depressive-like behaviours through affecting inflammatory pathways and neuron-associated gene ontologies.