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Variations in thermal environments can provoke diverse physiological responses in amphibians. Despite extensive studies on the thermal sensitivity of amphibian metabolic physiology, including enzyme activity at different temperatures, the rationale for selecting specific metabolic enzymes and their relationship with gene expression remains unclear. Cytochrome c oxidase (CCO), succinate dehydrogenase (SDH), and lactate dehydrogenase (LDH) are key metabolic enzymes within the primary metabolic regulatory tissues of animals. Through a comparative analysis of the effects of two different thermal conditions (12 and 18 °C) on the activities and mRNA expression levels of these enzymes within the kidney and liver tissues of a winter-breeding amphibian (Leptobrachium liui), with the field group during the breeding season as the control, we provide insights into the interplay between temperature and gene expression. The mRNA levels of CCO subunits 1 (cox1), 2 (cox2), and 3 (cox3), and LDH subunit A (ldha) were significantly higher in the kidney than in the liver of all individuals. High-temperature acclimation resulted in significantly decreased expression levels of cox1-3, ldha, and SDH complex flavoprotein subunit A (sdha) in the kidney. In the liver, the expression levels of sdha and ldha significantly reduced under high-temperature treatment, whereas cox3 expression increased. SDH and LDH activities displayed tissue-specific variations, while no significant differences in CCO activity were observed between tissues. CCO, SDH, and LDH activities in both liver and kidney tissues significantly declined after high-temperature acclimation, but simultaneously increased with up-regulated gene expression, indicating that the thermal environment and corresponding gene expression combined affect the activities of these metabolic enzymes. In conclusion, the thermal environment is a key factor affecting the physiological and biochemical responses of L. liui. Prolonged exposure to high temperatures during the breeding season could inhibit the activity of primary metabolic enzymes in the winter-breeding amphibian., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

We aimed to investigate the genomic and tumor microenvironmental (TME) profiles in non-muscle invasive bladder cancer (NMIBC) and explore potential predictive markers for Bacillus Calmette-Guérin (BCG) treatment response in high-risk NMIBC patients (according to European Association of Urology (EAU) risk stratification). 40 patients with high-risk NMIBC (cTis-T1N0M0) who underwent en bloc resection followed by BCG instillation were retrospectively enrolled. Surgical samples were subjected to Next Generation Sequencing (NGS) and multiplex immunofluorescence (mIF) assay. Genomic profiling revealed high prevalences of alterations in TERT (55%), KDM6A (32.5%), FGFR3(30%), PIK3CA (30%), TP53(27.5%) and ARID1A (20%). TME analysis showed different proportions of macrophages, NK cells, T cells subsets in tumoral and stromal compartment. Multivariate analysis identified TERT C228T and alteration in KDM6A as two independent factors associated with inferior RFS. The study comprehensively depicted the genomic and TME profiles in NMIBC and identified potential predictive biomarkers for BCG treatment., (© 2024. The Author(s).)

Purpose: Women with gestational diabetes mellitus (GDM) or obesity are vulnerable to impaired gestational cardiovascular health (CVH) and cardiovascular disease (CVD) in the future. It is unclear if prenatal vitamin D supplementation improves gestational CVH, especially in women at high risk for developing CVD. Our goal was to find out if vitamin D supplementation could protect against gestational CVH, including the women with GDM or obesity., Design: We randomly assigned women with a serum 25(OH)D concentration < 75 nmol/L to receive 1600 IU/d (intervention group) or 400 IU/d (control group) of vitamin D3 for two months at 24-28 weeks' gestation. The primary outcome was gestational CVH marks (lipids, inflammatory cytokines, endothelial function)., Results: There were 1537 participants divided into the intervention (N = 766) and control groups (N = 771). No baseline differences existed among study groups in CVH markers. At the two-month visit, the intervention group's HDL-C levels (2.01 ± 0.39 VS 1.96 ± 0.39 mmol/L) were significantly higher than those of the control group, while the hs-CRP levels were significantly lower (3.28 ± 2.02 VS 3.64 ± 2.42 mg/L). Subgroup analysis found that HDL-C, TC, hs-CRP, E-Selectin, and SBP were improved in the intervention group among women with GDM or overweight/obesity, and the improvement was not found in women without GDM or overweight/obesity. Vitamin D supplementation significantly decreased the mean triglyceride-glucose index at the two-month visit in women with GDM., Conclusions: Vitamin D supplementation at mid-gestation might optimize the gestational CVH status for pregnant women, particularly the women with GDM or obesity, which is advantageous for later-life primary prevention of CVD., Clinical Trial Registration: The Chinese Clinical Trial Registry (ChiCTR2100051914, 10/9/2021, Prospective registered, https://www.chictr.org.cn/showproj.aspx?proj=134700 )., (© 2024. Springer-Verlag GmbH Germany, part of Springer Nature.)

The Chinese horned toads, Boulenophrys boettgeri (Boulenger, 1899) and Boulenophrys kuatunensis (Pope, 1929), are two captivating species within the family Megophryidae, which inhabit the mountainous streams in the Eastern of China. In this study, two new complete mitochondrial genomes of B. boettgeri and B. kuatunensis were sequenced, assembled, and annotated using next-generation sequencing. The length of mitochondrial genomes of B. boettgeri and B. kuatunensis was 16,597 and 17,921 bp, respectively, with both containing 13 protein coding genes, 22 tRNA genes, two rRNA genes, and one putative control region. Phylogenetic relationships based on protein-coding mitochondrial genes showed that the two Boulenophrys species formed a cluster with other Boulenophrys species. The two new sequences provide valuable insights into the mitochondrial genomes of these two species, offering important data for understanding the phylogenetic relationships of the genus Boulenophrys ., Competing Interests: No potential conflict of interest was reported by the author(s)., (© 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.)

Aim: To compare relative peripheral refraction (RPR) in Chinese school children with different refractive errors using multispectral refraction topography (MRT)., Methods: A total of 713 eyes of primary school children [172 emmetropia (E), 429 low myopia (LM), 80 moderate myopia (MM), and 32 low hypermetropia (LH)] aged 10 to 13y were analyzed. RPRs were measured using MRT without mydriasis. MRT results showed RPR at 0-15° (RPR 0-15), 15°-30° (RPR 15-30), and 30°-45° (RPR 30-45) annular in the inferior (RPR-I), superior (RPR-S), nasal (RPR-N), and temporal (RPR-T) quadrants. Spherical equivalent (SE) was detected and calculated using an autorefractor., Results: There were significant differences of RPR 15-30 between groups MM [0.02 (-0.12; 0.18)] and LH [-0.13 (-0.36; 0.12)] ( P <0.05), MM and E [-0.06 (-0.20; 0.10)] ( P <0.05), and LM [-0.02 (-0.15; 0.15)] and E ( P <0.05). There were also significant differences of RPR 30-45 between groups MM [0.45 (0.18; 0.74)] and E [0.29 (-0.09; 0.67)] ( P <0.05), and LM [0.44 (0.14; 0.76)] and E ( P <0.001). RPR values increased from the hyperopic to medium myopic group in each annular. There were significant differences of RPR-S between groups MM [-0.02 (-0.60; 0.30)] and E [-0.44 (-0.89; -0.04)] ( P <0.001), and LM [-0.28 (-0.71; 0.12)] and E ( P <0.05). There were also significant differences of RPR-T between groups MM [0.37 (0.21; 0.78)] and LH [0.14 (-0.52; 0.50)] ( P <0.05), LM [0.41 (0.06; 0.84)] and LH ( P <0.05), and LM and E [0.29 (-0.10; 0.68), P <0.05]. A Spearman's correlation analysis showed a negative correlation between RPR and SE in the 15°-30° ( P =0.005), 30°-45° ( P <0.05) annular ( P =0.002), superior ( P <0.001), and temporal ( P =0.001) quadrants., Conclusion: Without pupil dilation, values for RPR 15-30, 30-45, RPR-S, and T shows significant differences between myopic eyes and emmetropia, and the differences are negatively correlated with SE., Competing Interests: Conflicts of Interest: Hu HL, None; Li SZC, None; Feng AY, None; Zhong HX, None; Mu JF, None; Liu MZ, None., (International Journal of Ophthalmology Press.)

Aim: To investigate the impact of hsa&#95;circ&#95;0007482 on the proliferation and apoptosis of human pterygium fibroblasts (HPFs) and its correlation with the severity grades of pterygium., Methods: Pterygium and normal conjunctival tissues were collected from the superior area of the same patient's eye ( n =33). The correlation between pterygium severity and hsa&#95;circ&#95;0007482 expression using quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were analyzed. Three distinct siRNA sequences targeting hsa&#95;circ&#95;0007482, along with a negative control sequence, were transfected into HPFs. Cell proliferation was assessed using the cell counting kit-8. Expression levels of Ki67, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bax, B-cell lymphoma-2 (Bcl-2), and Caspase-3 were measured via RT-qPCR. Immunofluorescence staining was employed to detect Ki67 and vimentin expressions. Apoptosis was evaluated using flow cytometry., Results: Hsa&#95;circ&#95;0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues ( P <0.001). Positive correlations were observed between hsa&#95;circ&#95;0007482 expression and pterygium severity, thickness, and vascular density. Knockdown of hsa&#95;circ&#95;0007482 inhibited cell proliferation, reducing the mRNA expression of Ki67, PCNA, and Cyclin D1 in HPFs. Hsa&#95;circ&#95;0007482 knockdown induced apoptosis, increasing mRNA expression levels of Bax and Caspase-3, while decreasing Bcl-2 expression in HPFs. Additionally, hsa&#95;circ&#95;0007482 knockdown attenuated vimentin expression in HPFs., Conclusion: The downregulation of hsa&#95;circ&#95;0007482 effectively hampers cell proliferation and triggers apoptosis in HPFs. There are discernible positive correlations detected between the expression of hsa&#95;circ&#95;0007482 and the severity of pterygium., Competing Interests: Conflicts of Interest: Zhang LY, None; Liu X, None; Zheng S, None; Xi WQ, None; Wu XP, None; Nie DY, None; Hu HL, None; Wang JT, None; Liu XH, None; Zhang J, None., (International Journal of Ophthalmology Press.)

Background: Group A streptococcal(GAS) meningitis is a severe disease with a high case fatality rate. In the era of increasing GAS meningitis, our understanding about this disease is limited., Purpose: To gain a better understanding about GAS meningitis., Methods: Five new cases with GAS meningitis were reported. GAS meningitis related literatures were searched for systematic review in PUBMED and EMBASE. Case reports and case series on paediatric cases were included. Information on demographics, risk factors, symptoms, treatments, outcomes, and emm types of GAS was summarized., Results: Totally 263 cases were included. Among 100 individuals, 9.9% (8/81) had prior varicella, 11.1% (9/81) had anatomical factors, and 53.2% (42/79) had extracranial infections. Soft tissue infections were common among infants (10/29, 34.5%), while ear/sinus infections were more prevalent in children ≥ 3 years (21/42, 50.0%). The overall case fatality rate (CFR) was 16.2% (12/74). High risk of death was found in patients with shock or systemic complications, young children(< 3 years) and cases related to hematogenic spread. The predominate cause of death was shock(6/8). Among the 163 patients included in case series studies, ear/sinus infections ranged from 21.4 to 62.5%, while STSS/shock ranged from 12.5 to 35.7%, and the CFR ranged from 5.9 to 42.9%., Conclusions: A history of varicella, soft tissue infections, parameningeal infections and CSF leaks are important clinical clues to GAS in children with meningitis. Young children and hematogenic spread related cases need to be closely monitored for shock due to the high risk of death., (© 2024. The Author(s).)

Background: The aim of this study was to characterize the variable phenotypes and outcomes associated with the methylmalonic aciduria and homocystinuria type C protein gene (MMACHC) c.482G > A mutation in 195 Chinese cases with CblC disease., Methods: We carried out a national, retrospective multicenter study of 195 Chinese patients with CblC disease attributable to the MMACHC c.482G > A variant either in a homozygous or compound heterozygous state. The control group consisted of 200 patients diagnosed with CblC disease who did not possess the c.482G > A mutation. Clinical features, including disease onset, symptoms, biochemical metabolites, gene mutation, and follow-up outcomes were reviewed and analyzed in detail. The median follow-up period spanned 3 years and 8 months, with a range of 1 year and 2 months to 12 years and 10 months., Results: Among 195 patients carrying the c.482G > A variant, 125 (64.1%) cases were diagnosed by newborn screening (NBS), 60 (30.8%) cases were detected due to disease onset, and 10 (5.1%) cases were identified from sibling diagnoses. One hundred and seventeen (93.6%) individuals who were diagnosed by NBS, and nine patients who came from sibling diagnoses remained asymptomatic in this study. From 69 symptomatic patients of the c.482G > A group, more patients presented with later onset, and the top six common clinical symptoms at disease onset were developmental delay (59.4%), lower limb weakness and poor exercise tolerance (50.7%), cognitive decline (37.7%), gait instability and abnormal posture (36.2%), seizures (26.1%), and psychiatric and behavioral disturbances (24.6%). In the 159 symptomatic patients lacking c.482G > A variants, the most frequently observed clinical manifestations at disease onset included developmental delay (81.8%), lethargy and feeding difficulty (62.9%), lower limb weakness and poor exercise tolerance (54.7%), prolonged neonatal jaundice (51.6%), vomiting (47.2%), and seizures (32.7%). Before treatment, the levels of blood propionylcarnitine, propionylcarnitine/acetylcarnitine ratio, and homocysteine in the c.482G > A group were significantly lower (P < 0.05) than those in the non-c.482G > A group, while the concentration of urinary methylmalonic acid was slightly lower (P > 0.05). The degree of decline in the above metabolites after treatment in different groups significantly differed in both plasma total homocysteine values and urinary methylmalonic acid levels (P < 0.05). In patients carrying the c.482G > A variant compared with the non-c.428G > A group, there were markedly lower rates of mortality (0.5% vs. 2.0%) and developmental delay (20.5% vs. 65.5%). When compared with individuals diagnosed due to disease onset, those identified through NBS in either group exhibited a reduced proportion of disease onset (6.7% vs. 100% in the c.482G > A group, 54.4% vs. 100% in the non-c.482G > A group), lower mortality (0.0% vs. 1.7% in the c.482G > A group, 0.0% vs. 3.6% in the non-c.482G > A group), and had a higher percentage of patients exhibiting normal psychomotor and language development (99.3% vs. 33.3% in the c.482G > A group, 58.9% vs. 10.9% in the non-c.482G > A group)., Conclusions: The c.482G > A variant in MMACHC is associated with late-onset and milder phenotypes of CblC disease. Patients with this mutation tend to have a relatively better response to hydroxocobalamin, better metabolic control, and more favorable neurological outcomes. NBS and other appropriate pre-symptomatic treatments seem to be helpful in early diagnosis, resulting in favorable clinical outcomes. Video Abstract (MP4 136794 kb)., (© 2023. The Author(s).)

The first amidation of carbazoles at the N9 position via palladium-catalyzed hydroamination of isocyanates is demonstrated. This simple, general and efficient method could deliver a wide range of carbazole- N -carboxamides in up to 99% yield. The salient features of this transformation include simple conditions with no need for a strong base, high chemo- and regio-selectivities and good functional group tolerance. In particular, this work-up-free and chromatography-free protocol is time-saving, cost-effective and user-friendly.

Background: Data on pyogenic liver abscess (PLA) of children in China have been limited. We aimed to summarize the clinical feather, microbiological characteristics, management, and outcome of PLA in children., Method: We retrospectively reviewed PLA cases from January 2008 to June 2023 at Beijing Children's Hospital. Clinical characteristics, pathogens and management were analyzed., Results: We diagnosed 57 PLA patients in our center. The median onset age was 4.5 years and the male-to-female ratio was 1.6:1. The median diagnostic time was nine days and the median length of stay was 22 days. Twenty-eight patients (49.1%) had predisposing factors, around 71.4% of the patients had malignant hematology and primary immunodeficiency disease. Patients with underlying factors were more likely to have extrahepatic organ involvement (p = 0.024), anemia (p < 0.001), single abscess (p = 0.042), unilateral involvement (p = 0.039), and small size of the abscess (p = 0.008). Twenty-four patients (42.1%) had extrahepatic organ involvement. Pathogens were identified in 17 patients (29.8%), the most common pathogens were Klebsiella pneumoniae and Staphylococcus aureus. The positive rate of metagenomic next-generation sequencing (mNGS) was 87.5% (7/8). On multivariable analysis, the extrahepatic organ involved (p = 0.029) and hepatomegaly (p = 0.025) were two independent factors associated with poor outcomes., Conclusions: PLA is usually seen in children with predisposing factors. Malignant hematology and primary immunodeficiency disease were the most common underlying diseases. Extrahepatic organ involvement and hepatomegaly are associated with poor prognosis. Increased use of mNGS could be beneficial for identifying pathogens., (© 2024. The Author(s).)

The existing surgery timetable is very simple, not user-friendly, and has very limited information. This article outlines the creation of a surgical dynamic dashboard for users, using Microsoft Power BI. The dashboard was developed based on in-depth interviews with the surgical team members to determine their requirements. The outcome of dashboard was evaluated by 5-likert scale questionnaire to measure satisfaction of all surgical team members. All team members were very satisfied with the dashboard compared to the existing surgery timetable. In addition, with the function of auto-generated analytic reports through data criteria selection on the dashboard saved time on manually generating reports. This study supports to replace the existing surgery timetable by the user-centric and real time surgical dashboard.

The achievement of covalent organic frameworks (COFs) with high stability and exceptional proton conductivity is of tremendous practical importance and challenge. Given this, we hope to prepare the highly stable COFs carrying CN connectors and enhance their proton conductivity via a post-modification approach. Herein, one COF, TpTta, was successfully synthesized by employing 1,3,5-triformylphloroglucinol (Tp) and 4,4',4″-(1,3,5-triazine-2,4,6-triyl)-trianiline (Tta) as starting materials, which has a β-ketoenamine structure bearing a large amount of -NH groups and intramolecular H-bonds. TpTta was then post-modified by inserting imidazole (Im) and histamine (His) molecules, yielding the corresponding COFs, Im@TpTta and His@TpTta, respectively. As a result, their proton conductivities were surveyed under changeable temperatures (30-100 °C) and relative humidities (68-98 %), revealing a degree of temperature and humidity dependence. Impressively, under identical conditions, the optimum proton conductivities of the two post-modified COFs are 1.14 × 10 -2 (Im@TpTta) and 3.45 × 10 -3 S/cm (His@TpTta), which are significantly greater than that of the pristine COF, TpTta (2.57 × 10 -5 S/cm). Finally, their proton conduction mechanisms were hypothesized based on the computed activation energy values, water vapor adsorption values, and structural properties of these COFs. Additionally, the excellent electrochemical stability of the produced COFs was expressed, as well as the prospective application value., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

ZnSeTe quantum dots (QDs) attract growing interest owing to their low threats to health and the environment. They are widely applied as emitters in displays and lighting devices. Previous findings have indicated that inorganic halides are excellent candidates for surface ligands on QDs. By incorporating inorganic halides during the synthesis process, the photoluminescence (PL) intensity and quantum yield (QY) of QDs can be significantly enhanced. However, the alteration of surface states in QDs induced by zinc halide modification and the mechanism of formation of trap-state radiative recombination processes have been less discussed. Herein, we proposed a synthesis strategy for ZnSeTe/ZnSe/ZnSeS/ZnS core/shell/shell/shell QDs modified with ZnCl 2 , and by comparing the morphology and elemental composition of QDs with different amounts of ZnCl 2 added, we revealed the regulatory mechanism of nanocrystal growth in the presence of ZnCl 2 . QDs with modification of ZnCl 2 exhibited broad yellow fluorescence, distinct from the intrinsic blue emission. Through spectroscopic and surface ligand analyses, we attributed this yellow emission to the intermediate state energy levels caused by the defects on the surface. Finally, we used the QDs with broad linewidth emission to fabricate a simple white-light-emitting diode (WLED). This work provided new insights into the role of inorganic ligands and the use of a single emitting material in solid-state lighting devices.

To date, developing crystalline proton-conductive metal-organic frameworks (MOFs) with an inherent excellent proton-conducting ability and structural stability has been a critical priority in addressing the technologies required for sustainable development and energy storage. Bearing this in mind, a multifunctional organic ligand, 3,4-dimethylthiophene[2,3- b ]thiophene-2,5-dicarboxylic acid (H 2 DTD), was employed to generate two exceptionally stable three-dimensional porous Zr/Hf MOFs, [Zr 6 O 4 (OH) 4 (DTD) 6 ]·5DMF·H 2 O ( Zr-DTD ) and [Hf 6 O 4 (OH) 4 (DTD) 6 ]·4DMF·H 2 O (Hf-DTD ), using solvothermal means. The presence of Zr 6 or Hf 6 nodes, strong Zr/Hf-O bonds, the electrical influence of the methyl group, and the steric effect of the thiophene unit all contribute to their structural stability throughout a wide pH range as well as in water. Their proton conductivity was fully examined at various relative humidities (RHs) and temperatures. Creating intricate and rich H-bonded networks between the guest water molecules, coordination solvent molecules, thiophene-S, -COOH, and -OH units within the framework assisted proton transfer. As a result, both MOFs manifest the maximum proton conductivity of 0.67 × 10 -2 and 4.85 × 10 -3 S·cm -1 under 98% RH/100 °C, making them the top-performing proton-conductive Zr/Hf-MOFs. Finally, by combining structural characteristics and activation energies, potential proton conduction pathways for the two MOFs were identified.

The issue of urban renewal is complex and multifaceted. In this study, six specialists in the construction industry were invited to conduct audio interviews, which were compiled into verbatim text. The key phrases were extracted by Grounded theory, and three levels of coding were retrieved. The data were categorized into ten accelerating urban renewal factors in three constructs to establish an Analytic Hierarchy Process framework. Using institutional theory to construct outcomes based on grounded theory, transforming these into specific urban renewal relation issue elements. 113 AHP questionnaires were collected from five types of specialists, including practitioners, professionals, participants in urban renewal, academics, and government staff. The results show that relaxing the plot ratio control and incentives is ranked No. 1 by practitioners, participants in urban renewal, professionals, and academics, indicating that the factor is highly valued by specialists but neglected by government staff. Secondly, practitioners, academics, participants in urban renewal, and professionals identified incentives and rewards for urban renewal and enhancing the trust and credibility of urban renewal projects as crucial factors. However, the government staff showed a different weighting. This indicates that government staff is determined to accelerate urban renewal. Finally, the suggestion of this study is in line with the views of the specialists interviewed, who suggest that the government should hold public hearings regularly and seriously to listen to people and specialists. Only through public hearings can all parties reach a consensus. The government should consolidate the views of all parties to amend or enact a bill on urban renewal that is more in line with the changes of the times, including appropriately relaxing the control of building plot ratio and other accelerating factors, to promote urban renewal in Taiwan., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Indium-based metal-organic frameworks (In-MOFs) have now become an attractive class of porous solids in materials science and electrochemistry due to their diverse structures and promising applications. In the field of proton conduction, to find more crystalline MOFs with splendid proton-conductive properties, herein, five three-dimensional isostructural In-MOFs, MIL-68-In or MIL-68-In-X (X = NH 2 , OH, Br, or NO 2 ) using terephthalic acid (H 2 BDC) or functionalized terephthalic acids (H 2 BDC-X) as multifunctional linkages were efficiently fabricated. First, the outstanding structural stability of the five MOFs, including thermal and water stability, was verified by thermal analysis and powder X-ray diffraction. Subsequently, the H 2 O-mediated proton conductivities (σ) were fully assessed and compared. Notably, their σ evinced a significant positive correlation between the temperature or relative humidity (RH) and varied with the functional groups on the organic ligands. Impressively, their highest σ values are up to 10 -3 -10 -4 S/cm (100 °C/98% RH) and change in this order: MIL-68-In-OH (1.72 × 10 -3 S/cm) > MIL-68-In-NH 2 (1.70 × 10 -3 S/cm) > MIL-68-In-NO 2 (4.47 × 10 -4 S/cm) > MIL-68-In-Br (4.11 × 10 -4 S/cm) > MIL-68-In (2.37 × 10 -4 S/cm). Finally, the computed activation energy values under 98 or 68% RHs are assessed, and the related proton conduction mechanisms are speculated. Moreover, after electrochemical testing, these MOFs illustrate remarkable structural rigidity, laying a meritorious material foundation for future applications.

Objective: Patients treated with preoperative chemotherapy and immunotherapy for bladder cancer may be at increased risk of cardiotoxicity and electrophysiological abnormalities. This study aimed to analyze their electrocardiographic (ECG) alterations., Methods: Patients with bladder cancer who were hospitalized and receiving tislelizumab plus nab-paclitaxel (TnP) were enrolled prospectively. ECG, cardiac biomarkers, and echocardiography were performed at baseline and the end of TnP., Results: A total of 60 patients (76.7% males), including 30 muscle-invasive and 30 non-muscle-invasive bladder cancer, received three or four cycles of TnP, respectively. Hypertension was the commonest comorbidity (41.7%), and 25 patients (41.7%) were prescribed cardiovascular drugs. In comparison with baseline characteristics, cardiac troponin I (cTnI) and N-terminal pro-brain natriuretic peptide (NT-proBNP) were within normal ranges after TnP. However, echocardiographic parameter of left ventricular ejection fraction slightly decreased after TnP (62.81 ± 3.81% to 61.10 ± 4.37%, p = .011). The incidence of abnormal ECG increased from 65.0% at baseline to 76.7%, of which only a higher prevalence of fragmented QRS (fQRS) was observed (33.3% to 50.0%, p = .013; mainly in inferior leads). ECG parameters of QT dispersion (QTd) were prolonged significantly after the regimen (39.50 ± 11.37 to 44.20 ± 15.85 ms, p = .019)., Conclusion: In bladder cancer patients receiving preoperative chemotherapy combined with immunotherapy, the main ECG abnormality was fQRS and QTd, with relatively normal cardiac biomarkers and echocardiographic parameters. Regular ECG screening should be carried out carefully to detect potential cardiotoxicity in the long-term follow-up., (© 2024 The Authors. Annals of Noninvasive Electrocardiology published by Wiley Periodicals LLC.)

Although numerous studies have been conducted on hybrid speciation, our understanding of this process remains limited. Through an 18-year systematic investigation of all taxa of Populus on the Qinghai-Tibet Plateau, we discovered three new taxa with clear characteristics of sect. Leucoides. Further evidence was gathered from morphology, whole-genome bioinformatics, biogeography, and breeding to demonstrate synthetically that they all originated from distant hybridization between sect. Leucoides and sect. Tacamahaca. P. gonggaensis originated from the hybridization of P. lasiocarpa with P. cathayana, P. butuoensis from the hybridization of P. wilsonii with P. szechuanica, and P. dafengensis from the hybridization of P. lasiocarpa with P. szechuanica. Due to heterosis, the three hybrid taxa possess greater ecological adaptability than their ancestral species. We propose a hybrid speciation process model that incorporates orthogonal, reverse, and backcrossing events. This model can adequately explain some crucial evolutionary concerns, such as the nuclear-cytoplasmic conflict on phylogeny and the extinction of ancestral species within the distribution range of hybrid species., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Circular RNAs (circRNAs) regulate the function of vascular smooth muscle cells (VSMCs) in atherosclerosis (AS) progression. We aimed to explore the role of circUSP9X in oxidized low-density lipoprotein (ox-LDL)-induced VSMCs. Cell proliferation was assessed using cell counting kit-8 and EDU assays. Cell migration was evaluated using Transwell and wound healing assays. The interaction between circUSP9X or STIM1 and miR-599 was analyzed using dual-luciferase reporter and RNA pull-down assays. Their levels were examined using quantitative real-time PCR. CircUSP9X and STIM1 expression was increased, whereas miR-599 expression was reduced in the serum of patients with AS and ox-LDL-stimulated VSMCs. Overexpression of circUSP9X facilitated the proliferation and migration of VSMCs induced by ox-LDL. CircUSP9X sponged miR-599, which targeted STIM1. MiR-599 reversed the effects induced by circUSP9X, and STIM1 reversed the effects induced by miR-599. Taken together, CircUSP9X promoted proliferation and migration in ox-LDL-treated VSMCs via the miR-599/STIM1 axis, providing a theoretical basis for the role of circUSP9X/miR-599/STIM1 axis in AS.

Safe and efficacious antiviral therapeutics are in urgent need for the treatment of coronavirus disease 2019. Simnotrelvir is a selective 3C-like protease inhibitor that can effectively inhibit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We evaluated the safety, tolerability, and pharmacokinetics of dose escalations of simnotrelvir alone or with ritonavir (simnotrelvir or simnotrelvir/ritonavir) in healthy subjects, as well as the food effect (ClinicalTrials.gov Identifier: NCT05339646). The overall incidence of adverse events (AEs) was 22.2% (17/72) and 6.3% (1/16) in intervention and placebo groups, respectively. The simnotrelvir apparent clearance was 135-369 L/h with simnotrelvir alone, and decreased significantly to 19.5-29.8 L/h with simnotrelvir/ritonavir. The simnotrelvir exposure increased in an approximately dose-proportional manner between 250 and 750 mg when co-administered with ritonavir. After consecutive twice daily dosing of simnotrelvir/ritonavir, simnotrelvir had a low accumulation index ranging from 1.39 to 1.51. The area under the curve of simnotrelvir increased 44.0 % and 47.3 % respectively, after high fat and normal diet compared with fasted status. In conclusion, simnotrelvir has adequate safety and tolerability. Its pharmacokinetics indicated a trough concentration above the level required for 90 % inhibition of SARS-CoV-2 in vitro at 750 mg/100 mg simnotrelvir/ritonavir twice daily under fasted condition, supporting further development using this dosage as the clinically recommended dose regimen., Competing Interests: Declaration of Competing Interest Yang Yang, Shao-Ping Peng, Yu-Mei Yang, Pan Shu, Pei-Jin Li, Shan Li, Hong-Lin Hu and Ren-Hong Tang are employees of Jiangsu Simcere Pharmaceutical Co., Ltd. Yan Xu is employee of Simcere of America. Other authors declare that they have no conflict of interest., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Hypertrophic cardiomyopathy (HCM) is a common cardiac genetic disorder that clinically manifests with sudden death and progressive heart failure. Moreover, thyroid dysfunction is associated with increased cardiovascular morbidity and mortality risks. Therefore, this study aimed to clarify whether thyroid hormones could serve as an independent predictor of adverse events in patients with HCM., Methods: The cohort consisted of 782 patients with HCM who had thyroid hormones baseline data and were admitted to the Affiliated Hospital of Jiaxing University. Patients were divided into two groups according to serum levels of free triiodothyronine (fT3): the normal fT3 and low triiodothyronine (T3) syndrome groups. Low T3 syndrome was defined as fT3 < 2.43 pmol/L with a normal thyroid-stimulating hormone (TSH) level. Patients whose TSH levels were abnormally high or abnormally low were excluded from this study. The primary endpoint was the occurrence of sudden cardiac death (SCD) events, and the secondary endpoint was a composite of worsening heart failure (WHF) events, including heart failure death, cardiac decompensation, hospitalization for heart failure, and HCM-related stroke. The Kaplan-Meier and Cox regression were performed for the survival analysis., Results: After a median follow-up of 52 months, 75 SCD events and 134 WHF events were recorded. The Kaplan-Meier survival curves showed that the cumulative incidence of SCD events and WHF events were significantly higher in patients with low T3 syndrome (log-rank p = .02 and log-rank p = .001, respectively). Furthermore, multivariate Cox regression analysis demonstrated that low T3 syndrome is a strong predictor of SCD events and WHF events (adjusted hazard ratio [HR: 1.53, 95% confidence interval [CI]: 1.13-2.24, p < .01; HR: 3.87, 95% CI: 2.91-4.98, p < .001, respectively)., Conclusions: Low T3 syndrome is highly prevalent among patients with HCM and was independently associated with an increased risk of SCD events and WHF events. The routine assessment of serum fT3 levels may provide risk stratification in this population., (© 2023 The Authors. Clinical Cardiology published by Wiley Periodicals, LLC.)

The genus Gandhara Moore, 1878 is reviewed. Four new species are described: Gandhara typica Volynkin & ern, sp. n. (Nepal, northeast India, northern Myanmar and northern Thailand), Gandhara clava Volynkin & ern, sp. n. (Laos and northern Thailand), Gandhara emgai Volynkin & ern, sp. n. (northern Vietnam), and Gandhara interrogativa Volynkin, ern, S.-Y. Huang & H.-L. Hu, sp. n. (northern Vietnam and southern China). Gandhara typica sp. n. is fixed as the type species of the genus Gandhara whereas Lithosia serva Walker, 1854 considered by authors as the type species of Gandhara by misidentification is transferred to the genus Collita Moore, 1878. Two new combinations are introduced: Gandhara conica (Fang, 2000), comb. n. and Collita serva (Walker, 1854), comb. n. A lectotype is designated for Lithosia serva Walker, 1854 in order to stabilise the nomenclature. Adults as well as male and female genitalia are illustrated.

The effect of time-restricted eating (TRE) has been summarized in previous studies, but its benefits in combination with calorie restriction (CR) still need to be determined. The present meta-analysis aimed to evaluate the efficacy of TRE with CR on weight loss and cardiometabolic risk. PubMed, Embase, Cochrane Library, and gray literature databases were searched from inception to October 18, 2022, for potential randomized controlled trial (RCT) studies based on predefined inclusion and exclusion criteria. Body weight and other cardiometabolic risk factors were described as weighted mean difference (WMD) with a 95% confidence interval (CI). Eight RCTs involving 579 participants were enrolled in the present analysis. The pooled results showed that TRE with CR reduced the body weight, fat mass, and waist circumference significantly (WMD: -1.40, 95% CI: -1.81 to -1.00, and I 2 : 0%; WMD: -0.73, 95% CI: -1.39 to -0.07, and I 2 : 0%; WMD: -1.87, 95% CI: -3.47 to -0.26, and I 2 : 67.25%, respectively). However, compared with CR alone, TRE plus CR exhibited no significant benefit on the blood pressure, glucose profile, and lipid profile. Subgroup analysis suggested that early TRE is more effective in weight loss (WMD: -1.42, 95% CI: -1.84 to -1.01, and I 2 : 0%) and improving fat mass (WMD: -1.06, 95% CI: -1.91 to -0.22, and I 2 : 0%) than delayed or broader TRE when combined with CR. Although the combination of TRE and CR can effectively decrease body weight, fat mass, and waist circumference, the long-term effects, particularly those on cardiometabolic risk in participants with chronic cardiovascular disease and diabetes, remain to be explored., (© 2023. The Author(s).)

Background: The microtubule protein inhibitor C118P shows excellent anti-breast cancer effects. However, the potential targets and mechanisms of C118P in breast cancer remain unknown., Methods: Real-time cellular analysis (RTCA) was used to detect cell viability. Apoptosis and the cell cycle were detected by flow cytometry. Computer docking simulations, surface plasmon resonance (SPR) technology, and microscale thermophoresis (MST) were conducted to study the interaction between C118P and alanine-serine-cysteine transporter 2 (ASCT2). Seahorse XF technology was used to measure the basal oxygen consumption rate (OCR). The effect of C118P in the adipose microenvironment was explored using a co-culture model of adipocytes and breast cancer cells and mouse cytokine chip., Results: C118P inhibited proliferation, potentiated apoptosis, and induced G2/M cell cycle arrest in breast cancer cells. Notably, ASCT2 was validated as a C118P target through reverse docking, SPR, and MST. C118P suppressed glutamine metabolism and mediated autophagy via ASCT2. Similar results were obtained in the adipocyte-breast cancer microenvironment. Adipose-derived interleukin-6 (IL-6) promoted the proliferation of breast cancer cells by enhancing glutamine metabolism via ASCT2. C118P inhibited the upregulation of ASCT2 by inhibiting the effect of IL-6 in co-cultures., Conclusion: C118P exerts an antitumour effect against breast cancer via the glutamine transporter ASCT2.

Objective: To study the effect and mechanism of post-ischemic treatment of nalmefene in alleviating the lung ischemia-reperfusion injury by inhibiting ferroptosis through activation of the Sirt 1/Nrf 2/HO-1 axis. Methods: A total of 60 rats were randomly divided into six groups equally ( n =10): the sham group, the model group(I/R), the nalmefene group, the nalmefene+EX527 group, the nalmefene+ML385 group, the nalmefene+Fe-citrate group (nalmefene+Fe group). The sham group without drug treatment was not treated with ischemia-reperfusion. The pulmonary ischemia-reperfusion model was established by occlusion of the left pulmonary hilum in the model group without drug treatment. After ischemic treatment, the nalmefene group was injected with nalmefene (15 μg/kg) via the tail vein at 5 minutes before reperfusion. The nalmefene+EX527 group, the nalmefene+ML385 group, and the nalmefene+Fe group were injected intraperitoneally with EX527 (5 mg/kg), ML385 (30 mg/kg), Fe-citrate(15 mg/kg), respectively, 2 h before moulding and then injected with nalmefene (15 μg/kg) via the tail vein at 5 minutes before reperfusion. All rats were sacrificed three hours after reperfusion, and the specimens from the upper lobe of the left lung tissue were preserved. The degree of lung tissue injury and the wet/dry weight ratio were assessed in each group of rats. Fe 2+ , MDA, TNF-α, and IL-6 content, GSH activity and the expression levels of Sirt1, Nrf2, HO-1, ACSL4 and GPX4 were determined. Results: Compared with the sham group, the wet/dry weight ratio, lung tissue injury score, ACSL 4 expression level, Fe 2+ , TNF-α, IL-6 and MDA content, Sirt 1, Nrf 2, HO-1 messenger RNA and protein expression levels were significantly increased ( P< 0.01), while GPX 4 expression level and GSH activity were significantly decreased in the model group ( P< 0.01). Compared with the model group, wet/dry weight ratio, lung tissue injury score, ACSL 4 expression level, Fe 2+ , TNF-α, IL-6, and MDA content decreased significantly ( P< 0.01), Nrf 2, HO-1 messenger RNA and protein, GPX 4 expression, and GSH activity were significantly increased in the nalmefene group and the nalmefene+EX527 group ( P< 0.01). Sirt 1 messenger RNA and protein expression increased significantly in the nalmefene ( P <0.01) and the nalmefene+EX527 groups ( P >0.05). In the nalmefene+ML385 group, the wet/dry weight ratio, lung tissue injury score, TNF-α and IL-6 content were decreased significantly ( P <0.01), while Sirt 1 messenger RNA and protein expression levels were significantly increased ( P <0.01), but there were no significant changes in Nrf 2, HO-1 messenger RNA and protein expression levels, ACSL 4 and GPX 4 expression levels, Fe 2+ , MDA content, and GSH activity ( P >0.05). In the nalmefene+Fe group, wet/dry weight ratio, lung-injury score, TNF-α, IL-6, MDA content were decreased significantly ( P< 0.01), messenger RNA and protein expression levels of Sirt 1, Nrf 2, HO-1, and GSH activity were increased significantly ( P< 0.01), but there were no significant changes in Fe 2+ content, ACSL 4 and GPX 4 expression levels ( P >0.05). Compared with the nalmefene group, in the nalmefene+EX527 group, the nalmefene+ML385 group and the nalmefene+Fe group, wet/dry weight ratio, lung tissue damage score, ACSL 4 expression level, TNF-α, IL-6 and MDA content were significantly increased ( P <0.01), the expression level of GPX 4 and GSH activity were significantly decreased ( P <0.01). The expression levels of Sirt 1, Nrf 2, HO-1 messenger RNA and protein were significantly decreased in the nalmefene+EX527 group ( P <0.01). The expression levels of Nrf 2, HO-1 messenger RNA and protein decreased significantly in the namemefene+ML385 group ( P< 0.01), but there was no significant change in Sirt 1 messenger RNA and protein expression level ( P >0.05). Sirt 1, Nrf 2, HO-1 messenger RNA-protein expression levels did not change significantly in the nalmefene+Fe group ( P >0.05). Conclusion: Post-ischemic treatment with nalmefene hydrochloride may alleviate pulmonary ischemia-reperfusion injury by inhibiting ferroptosis through activation of the Sirt 1/Nrf 2/HO-1 axis.

Patients diagnosed with cancer face an increased risk of cardiovascular events in the short term, while those experiencing acute myocardial infarction (AMI) have a higher incidence of cancer. Given limitations in clinical resources, identifying shared biomarkers offers a cost-effective approach to risk assessment by minimizing the need for multiple tests and screenings. Hence, it is crucial to identify common biomarkers for both cancer survival and AMI prediction. Our study suggests that monocyte-derived biomarkers, specifically WEE1, PYHIN1, SEC61A2, and HAL, hold potential as predictors for cancer prognosis and AMI. We employed a novel formula to analyze mRNA levels in clinical samples from patients with AMI and cancer, resulting in the development of a new risk score based on expression profiles. By categorizing patients into high-risk and low-risk groups based on the median risk score, we observed significantly poorer overall survival among high-risk patients in cancer cohorts using Kaplan-Meier analysis. Furthermore, calibration curves, decision curve analysis (DCA), and clinical impact curve analyses provided additional evidence supporting the robust diagnostic capacity of the risk score for AMI. Noteworthy is the shared activation of the Notch Signaling pathway, which may shed light on common high-risk factors underlying both AMI and cancer. Additionally, we validated the differential expression of these genes in cell lines and clinical samples, respectively, reinforcing their potential as meaningful biomarkers. In conclusion, our study demonstrates the promise of mRNA levels as biomarkers and emphasizes the significance of further research for validation and refinement., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Yuan, Pan, Liang, Hu, Zhai and Wang.)

Objective: An analysis was conducted to explore the relationship between dietary fibre intake and stroke risk., Methods: PubMed, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI) and WanFang and Weipu databases were systematically searched to obtain peer-reviewed literature on the relationship between dietary fibre and stroke risk. The search time was as of 1 April 2023. Newcastle-Ottawa Scale (NOS) was used to evaluate the quality of the included studies. The pooled hazard ratio (HR) and 95% confidence interval (CI) were calculated using Stata 16.0. The Q test and I 2 statistics were used to evaluate the heterogeneity and sensitivity analysis to explore potential bias. Meta-regression analysis was conducted to explore the relationship between total dietary intake quality and stroke risk., Results: Sixteen high-quality studies, involving 855,671 subjects, met the inclusion criteria and were involved in the final meta-analysis. The results showed that higher total dietary fibre (HR: 0.81; 95% CI: 0.75-0.88), fruit fibre (HR: 0.88; 95% CI: 0.82-0.93), vegetable fibre (HR: 0.85; 95% CI: 0.81-0.89), soluble fibre (HR: 0.82; 95% CI: 0.72-0.93) and insoluble fibre (HR: 0.77; 95% CI: 0.66-0.89) had a positive effect on reducing the risk of stroke. However, cereal fibre (HR: 0.90; 95% CI: 0.81-1.00) was not statistically significant in reducing the risk of stroke. For different stroke types, higher total dietary fibre was associated with ischemic stroke (HR: 0.83; 95% CI: 0.79-0.88) and had a similar positive effect but was not found in haemorrhagic stroke (HR: 0.91; 95% CI: 0.80-1.03). Stroke risk decreased with increased total dietary fibre intake (β=-0.006189, P=0.001). No potential bias from the individual study was found from sensitivity analysis., Conclusion: Increasing dietary fibre intake had a positive effect on reducing the risk of stroke. Different dietary fibres have various effects on stroke., Competing Interests: Declaration of Competing Interest All of the authors had no any personal, financial, commercial, or academic conflicts of interest separately, (Copyright © 2023. Published by Elsevier Inc.)

The activation of the α-C-H bond of ketones typically requires an amine and a directing group to guide the reaction selectivity in amine-catalysis carbonyl chemistry. For an α-C-H bond activation of ketone, directing groups are also required to control the reaction selectivity. Reported herein is the first α-alkylation of cyclic ketones in the absence of an amine catalyst and directing group. 1 H NMR, XPS, EPR studies and DFT calculations indicate that an α-carbon radical intermediate is formed through direct and selective activation of the inert α-C-H bond of ketones chelating on the surface of colloidal quantum dots (QDs). Such an interaction is essential for weakening the C-H bond, as exemplified, using CdSe QDs as the sole photocatalyst to execute α-C-H alkylation of cyclic ketones under visible-light irradiation. Without an amine catalyst and directing group, the high step- and atom-economy transformation under redox-neutral condition opens a new way for α-C-H functionalization of ketones in carbonyl chemistry., (© 2023 Wiley-VCH GmbH.)

Classic experiments with peripheral sympathetic neurons established an absolute dependence upon NGF for survival. A forgotten problem is how these neurons become resistant to deprivation of trophic factors. The question is whether and how neurons can survive in the absence of trophic support. However, the mechanism is not understood how neurons switch their phenotype to lose their dependence on trophic factors, such as NGF and BDNF. Here, we approach the problem by considering the requirements for trophic support of peripheral sympathetic neurons and hippocampal neurons from the central nervous system. We developed cellular assays to assess trophic factor dependency for sympathetic and hippocampal neurons and identified factors that rescue neurons in the absence of trophic support. They include enhanced expression of a subunit of the NGF receptor (Neurotrophin Receptor Homolog, NRH) in sympathetic neurons and an increase of the expression of the glucocorticoid receptor in hippocampal neurons. The results are significant since levels and activity of trophic factors are responsible for many neuropsychiatric conditions. Resistance of neurons to trophic factor deprivation may be relevant to the underlying basis of longevity, as well as an important element in preventing neurodegeneration., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Hu, Khatri, Santacruz, Church, Moore, Huang and Chao.)

Users of mobile phone applications (apps) often have to wait for the pages of apps to load, a process that substantially affects user experience. Based on the Attentional Gate Model and Emotional Contagion Theory, this paper explores the effects of the urgency expressed by a spokes-character's movement in the loading page of a social app the app type on users' switching intention through two studies. In Study 1 ( N  = 173), the results demonstrated that for a hedonic-orientated app, a high-urgency (vs. low-urgency) spokes-character resulted in a lower switching intention, whereas the opposite occurred for a utilitarian-orientated app. We adopted a similar methodology in Study 2 ( N  = 182) and the results showed that perceived waiting time mediated the interaction effect demonstrated in Study 1. Specifically, for the hedonic-orientated (vs. utilitarian-orientated) social app, the high-urgency (vs. low-urgency) spokes-character made participants estimate a shorter perceived waiting time, which induces a lower user switching intention. This paper contributes to the literature on emotion, spokes-characters, and human-computer interaction, which extends an enhanced understanding of users' perception during loading process and informs the design of spokes-characters for the loading pages of apps., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Hu, Tso and Liu.)

CX3C chemokine ligand 1 (CX3CL1) belongs to the CX3C chemokine family and is involved in various disease processes. However, its role in intervertebral disc degeneration (IDD) remains to be elucidated. In the present study, western blotting, reverse transcription-quantitative PCR and ELISA assays were used to assess target gene expression. In addition, immunofluorescence and TUNEL staining were used to assess macrophage infiltration, monocyte migration and apoptosis. The present study aimed to reveal if and how CX3CL1 regulates IDD progression by exploring its effect on macrophage polarization and apoptosis of human nucleus pulposus cells (HNPCs). The data showed that CX3CL1 bound to CX3C motif chemokine receptor 1 (CX3CR1) promoted the M2 phenotype polarization via JAK2/STAT3 signaling, followed by increasing the secretion of anti-inflammatory cytokines from HNPCs. In addition, HNPC-derived CX3CL1 promoted M2 macrophage-derived C-C motif chemokine ligand 17 release thereby reducing the apoptosis of HNPCs. In clinic, the reduction of mRNA and protein levels CX3CL1 in degenerative nucleus pulposus tissues (NPs) was measured. Increased M1 macrophages and pro-inflammatory cytokines were found in NPs of IDD patients with low CX3CL1 expression. Collectively, these findings suggested that the CX3CL1/CX3CR1 axis alleviates IDD by reducing inflammation and apoptosis of HNPCs via macrophages. Therefore, targeting CX3CL1/CX3CR1 axis is expected to produce a new therapeutic approach for IDD., Competing Interests: The authors declare that they have no competing interests., (Copyright: © Gao et al.)

Hypertensive nephropathy (HTN) ranks as the second-leading cause of end-stage renal disease (ESRD). Accumulating evidence suggests that persistent hypertension injures tubular cells, leading to tubulointerstitial fibrosis (TIF), which is involved in the pathogenesis of HTN. G protein-coupled receptors (GPCRs) are implicated in many important pathological and physiological processes and act as important drug targets. In this study, we explored the intrarenal mechanisms underlying hypertension-associated TIF, and particularly, the potential role of GPR97, a member of the adhesion GPCR subfamily, in TIF. A deoxycorticosterone acetate (DOCA)/salt-induced hypertensive mouse model was used. We revealed a significantly upregulated expression of GPR97 in the kidneys, especially in renal tubules, of the hypertensive mice and 10 patients with biopsy-proven hypertensive kidney injury. GPR97 -/- mice showed markedly elevated blood pressure, which was comparable to that of wild-type mice following DOCA/salt treatment, but dramatically ameliorated renal injury and TIF. In NRK-52E cells, we demonstrated that knockdown of GPR97 suppressed the activation of TGF-β signaling by disturbing small GTPase RhoA-mediated cytoskeletal reorganization, thus inhibiting clathrin-mediated endocytosis of TGF-β receptors and subsequent Smad activation. Collectively, this study demonstrates that GPR97 contributes to hypertension-associated TIF at least in part by facilitating TGF-β signaling, suggesting that GPR97 is a pivotal intrarenal factor for TIF progression under hypertensive conditions, and therapeutic strategies targeting GPR97 may improve the outcomes of patients with HTN., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)