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Aims: Advanced glycation end-products (AGEs) are implicated in the age-related decline of renal function, exacerbated by conditions, such as hyperglycemia and oxidative stress. The accumulation of AGEs in the kidneys contributes to the progressive decline in renal function observed with aging. However, the precise role and mechanisms of AGEs in the age-related decline of renal function remain unclear. In this study, we investigated the impact and potential mechanisms of AGEs on aging kidneys in naturally aging mice., Materials and Methods: Male C57BL/6 mice were divided into three groups: 6-, 57-, and 107-week-old. First, the 6- and 107-week-old mice were euthanized. The remaining mice were divided into young (6 weeks) and old (57 weeks) groups. The 57-week-old mice were orally administered aminoguanidine (100 mg/kg/day), an AGEs inhibitor, or vehicle for 13 weeks, resulting in a final age of 70 weeks. The serum and kidney tissues were collected for biochemical measurement, histological examination, immunohistochemistry staining, and immunoblotting analysis., Key Findings: Our findings revealed a notable accumulation of AGEs in both serum and kidney tissue specimens and renal dysfunction in naturally aging mice. Aminoguanidine not only reversed AGEs accumulation but also ameliorated renal dysfunction. Additionally, aminoguanidine attenuated the upregulation of fibrosis markers (phosphorylated p38/α-SMA and C/EBP homologous protein, CHOP), senescence markers (p53 and p21), and oxidative stress marker (4-HNE) in the aging kidneys., Significance: These findings underscore the critical role of AGEs in age-related renal dysfunction and highlight the therapeutic potential of aminoguanidine in mitigating fibrosis and senescence, offering prospective avenues for combating age-associated renal ailments., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest related to this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: To determine the independent effect of high-sensitivity C-reactive protein (hs-CRP) and the combined effects of hs-CRP and other traditional risk factors on microalbuminuria in hypertensive patients during the 3-year follow-up period., Methods and Results: Baseline hs-CRP levels and other risk factors were measured in 280 adults in 2007. In the third year of examination, 199 patients (mean age 62.5 ± 9.5, men 59.3%) were approached for the measurement of microalbuminuria. The subjects were classified into two groups by the median of baseline hs-CRP. Compared to the patients with baseline hs-CRP below the median group ( n  = 99, 50%), the group with baseline hs-CRP above the median ( n  = 100, 50%) had higher urinary albumin-to-creatinine ratio (ACR) ( P  = 0.007) at the end of follow-up period. ACR at the end of follow-up period was significantly correlated with baseline diabetes ( β  = 0.342; P  < 0.001), baseline SBP ( β  = 0.148; P  = 0.02), and baseline log-transformed hs-CRP ( β  = 0.169; P  = 0.01), while adversely correlated with baseline estimated glomerular filtration rate (eGFR) ( β  = -0.163; P  = 0.02) in multivariate stepwise linear analysis. In addition, ACR change during follow-up period was significantly correlated with baseline diabetes ( β  = 0.359; P  < 0.001) and baseline log-transformed hs-CRP ( β  = 0.190; P  = 0.004) in multivariate stepwise linear analysis. The combined effects of baseline hs-CRP and conventional risk factors, such as male sex, diabetes, smoking status, hyperlipidemia, hyperuricemia, and mildly reduced eGFR had a greater risk for microalbuminuria progression. There was no difference in eGFR changes during the follow-up period between two groups., Conclusion: Our findings offer a new piece of evidence on the predictive value of baseline hs-CRP for microalbuminuria progression in essential hypertensive patients, and highlight those who combined with traditional cardiovascular risk factors had a greater risk for developing microalbuminuria., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: β3-AR (β3-adrenergic receptor) is essential for cardiovascular homeostasis through regulating adipose tissue function. Perivascular adipose tissue (PVAT) has been implicated in the pathogenesis of aortic dissection and aneurysm (AD/AA). Here, we aim to investigate β3-AR activation-mediated PVAT function in AD/AA., Methods and Results: Aortas from patients with thoracic aortic dissection (TAD) were collected to detect β3-AR expression in PVAT. ApoE-/- and β-aminopropionitrile monofumarate (BAPN)-treated C57BL/6 mice were induced with Angiotensin II (AngII) to simulate AD/AA, and subsequently received either placebo or mirabegron, a β3-AR agonist. The results demonstrated an up-regulation of β3-AR in PVAT of TAD patients and AD/AA mice. Moreover, activation of β3-AR by mirabegron significantly prevented AngII-induced AD/AA formation in mice. RNA-sequencing analysis of adipocytes from PVAT revealed a notable increase of the lymphangiogenic factor VEGF-C in mirabegron-treated mice. Consistently, enhanced lymphangiogenesis was found in PVAT with mirabegron treatment. Mechanistically, the number of CD4+/CD8+ T cells and CD11c+ cells was reduced in PVAT but increased in adjacent draining lymph nodes (LNs) of mirabegron-treated mice, indicating the improved draining and clearance of inflammatory cells in PVAT by lymphangiogenesis. Importantly, adipocyte-specific VEGF-C knockdown by the adeno-associated virus system restrained lymphangiogenesis and exacerbated inflammatory cell infiltration in PVAT, which ultimately abolished the protection of mirabegron on AD/AA. In addition, the conditional medium derived from mirabegron-treated adipocytes activated the proliferation and tube formation of lymphatic endothelial cells (LECs), which was abrogated by the silencing of VEGF-C in adipocytes., Conclusions: Our findings illustrated the therapeutic potential of β3-AR activation by mirabegron on AD/AA, which promoted lymphangiogenesis by increasing adipocyte-derived VEGF-C and, therefore, ameliorated PVAT inflammation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Background: Increasing evidence indicates a close relationship between alterations in human immune cells and plasma metabolites with Rheumatoid Arthritis (RA). However, limited studies have left the causal relationships behind these links unclear., Methods: A bidirectional Mendelian Randomization (MR) study was conducted, combined with mediation analysis, using data from genome-wide association study database covering 731 immune cell phenotypes and 1,400 plasma metabolite traits to explore their causal relationships with RA and potential mediating effects. The primary method used for MR analysis was inverse-variance weighted and False Discovery Rate (FDR) correction was applied to verify the robustness of our results., Results: HLA DR on CD33- HLA DR+ (myeloid cell group) (OR, 1.422; 95% CI, 1.194-1.694; P < 0.001; P FDR = 0.012) increased the risk of developing RA. CD19 on IgD+ CD38- naive (B cell group) (OR, 0.969; 95% CI, 0.954-0.985; P < 0.001; P FDR = 0.021) reduced the risk of developing RA. RA was a risk factor for HLA DR on CD14- CD16+ monocytes (monocyte group) (OR, 1.242; 95% CI, 1.102-1.401; P < 0.001; P FDR  = 0.047). RA was a protective factor for memory B cell %lymphocyte (B cell group) (OR, 0.861; 95% CI, 0.795-0.933; P < 0.001; P FDR  = 0.050), CD4+ CD8dim T cell %lymphocyte (TBNK group) (OR, 0.802; 95% CI, 0.711-0.904; P < 0.001; P FDR  = 0.043), CD4+ CD8dim T cell %leukocyte (TBNK group) (OR, 0.814; 95% CI, 0.726-0.913; P < 0.001; P FDR  = 0.046), CD24 on IgD+ CD24+ B cells (B cell group) (OR, 0.857; 95% CI, 0.793-0.927; P < 0.001; P FDR  = 0.038), and CD24 on unswitched memory B cells (B cell group) (OR, 0.867; 95% CI, 0.797-0.942; P < 0.001; P FDR  = 0.050). Increasing levels of docosatrienoate (22:3n3) (OR, 0.886; 95% CI, 0.838-0.936; P < 0.001; P FDR  = 0.023) significantly reduced the risk of developing RA. The mediating effect of plasma metabolites in this context was not established., Conclusion: This study provides genetic evidence for the intricate relationships between immune cells, plasma metabolites, and RA, highlighting the potential mechanisms involved. This will contribute to future directions in precision medicine and research., 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 © 2024 Liu, Du, Xie and Chai.)

Natriuretic peptide receptor-C (NPR-C) is highly expressed in adipose tissues and regulates obesity-related diseases; however, the detailed mechanism remains unknown. In this research, we aimed to explore the potential role of NPR-C in cold exposure and high-fat/high-sugar (HF/HS) diet-induced metabolic changes, especially in regulating white adipose tissue (WAT) mitochondrial function. Our findings showed that NPR-C expression, especially in epididymal WAT (eWAT), was reduced after cold exposure. Global Npr3 (gene encoding NPR-C protein) deficiency led to reduced body weight, increased WAT browning, thermogenesis, and enhanced expression of genes related to mitochondrial biogenesis. RNA-sequencing of eWAT showed that Npr3 deficiency enhanced the expression of mitochondrial respiratory chain complex genes and promoted mitochondrial oxidative phosphorylation in response to cold exposure. In addition, Npr3 KO mice were able to resist obesity induced by HF/HS diet. Npr3 knockdown in stromal vascular fraction (SVF)-induced white adipocytes promoted the expression of proliferator-activated receptor gamma coactivator 1α (PGC1α), uncoupling protein one (UCP1), and mitochondrial respiratory chain complexes. Mechanistically, NPR-C inhibited cGMP and calcium signaling in an NPR-B-dependent manner but suppressed cAMP signaling in an NPR-B-independent manner. Moreover, Npr3 knockdown induced browning via AKT and p38 pathway activation, which were attenuated by Npr2 knockdown. Importantly, treatment with the NPR-C-specific antagonist, AP-811, decreased WAT mass and increased PGC-1α, UCP1, and mitochondrial complex expression. Our findings reveal that NPR-C deficiency enhances mitochondrial function and energy expenditure in white adipose tissue, contributing to improved metabolic health and resistance to obesity., Competing Interests: Conflict of interest The authors declare that they have no conflict of interest with the contents of this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Protein biogenesis within the endoplasmic reticulum (ER) is crucial for organismal function. Errors during protein folding necessitate the removal of faulty products. ER-associated protein degradation and ER-phagy target misfolded proteins for proteasomal and lysosomal degradation. The mechanisms initiating ER-phagy in response to ER proteostasis defects are not well understood. By studying mouse primary cells and patient samples as a model of ER storage disorders (ERSDs), we show that accumulation of faulty products within the ER triggers a response involving SESTRIN2, a nutrient sensor controlling mTORC1 signaling. SESTRIN2 induction by XBP1 inhibits mTORC1's phosphorylation of TFEB/TFE3, allowing these transcription factors to enter the nucleus and upregulate the ER-phagy receptor FAM134B along with lysosomal genes. This response promotes ER-phagy of misfolded proteins via FAM134B-Calnexin complex. Pharmacological induction of FAM134B improves clearance of misfolded proteins in ERSDs. Our study identifies the interplay between nutrient signaling and ER quality control, suggesting therapeutic strategies for ERSDs., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: There are few large-scale analyses comparing local tumor destruction (LTD) or local tumor enucleation/excision (LTE) relative to partial nephrectomy (PN) for patients with T1a renal masses in terms of cancer-specific survival (CSS) and overall survival (OS). The authors aimed to compare CSS and OS after LTD versus LTE versus PN., Materials and Methods: Within the Surveillance, Epidemiology, and End Results (SEER) database (2000-2019), the authors identified patients with clinical T1a renal masses and histologically confirmed kidney cancer treated with LTD, LTE, or PN. After 1:1 ratio propensity score matching (PSM), comparisons between the groups were conducted. Kaplan-Meier analysis and log-rank tests were used to compare survival in the matched population., Results: In the overall cohort of 3717 LTD patients versus 1993 LTE patients versus 26 935 PN patients, 77.3% of LTD-treated patients and 74.4% of LTE-treated patients were over 60 years old, while only 50.3% of PN-treated patients were over 60 years old. PN was more strongly associated with CSS [hazard ratio ((HR)=1.276, P <0.001) and OS (HR=1.112, P <0.001)] than was LTD, while PN was less strongly associated with CSS (HR=1.040, P =0.230) and OS (HR=0.888, P =0.002) than was LTE, not only in the PSM cohort but also in the subgroups of patients with a tumor size ≤3 cm and patients with a tumor size of 3.1-4 cm., Conclusions: In clinical T1a solid renal mass patients, LTD was associated with lower CSS and OS than LTE and PN, while LTE demonstrated noninferior CSS and superior OS to PN regardless of tumor size., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Purpose: Activation of mitogen-activated protein kinases (MAPKs) by pathological stimuli participates in cardiovascular diseases. Dysfunction of adventitial fibroblast has emerged as a critical regulator in vascular remodeling, while the potential mechanism remains unclear. In this study, we sought to determine the effect of different activation of MAPKs in adventitial fibroblast contributing to neointima formation., Methods: Balloon injury procedure was performed in male 12-week-old Sprague-Dawley rats. After injury, MAPK inhibitors were applied to the adventitia of injured arteries to suppress MAPK activation. Adventitial fibroblasts were stimulated by platelet-derived growth factor-BB (PDGF-BB) with or without MAPK inhibitors. RNA sequencing was performed to investigate the change of pathway and cell function. Wound healing, transwell assay, and flow cytometry were used to analyze adventitial fibroblast function., Results: Phosphorylation of p38, c-Jun N-terminal kinase (JNK), and extracellular regulated kinases 1/2 (ERK1/2) was increased in injured arteries after balloon injury. In primary culture of adventitial fibroblasts, PDGF-BB increased phosphorylation of p38, JNK, ERK1/2, and extracellular regulated kinase 5 (ERK5) in a short time, which was normalized by their inhibitors respectively. Compared with the injury group, perivascular administration of four MAPK inhibitors significantly attenuated neointima formation by quantitative analysis of neointimal area, intima to media (I/M) ratio, and lumen area. RNA sequencing of adventitial fibroblasts treated with PDGF-BB with or without four inhibitors demonstrated differentially expressed genes involved in multiple biological processes, including cell adhesion, proliferation, migration, and inflammatory response. Wound healing and transwell assays showed that four inhibitors suppressed PDGF-BB-induced adventitial fibroblast migration. Cell cycle analysis by flow cytometry demonstrated that JNK, ERK1/2, and ERK5 but not p38 inhibitor blocked PDGF-BB-induced G1 phase release associated with decrease expression of cell cycle protein Cyclin D1 and transcription factor GATA4. Moreover, four inhibitors decreased macrophage infiltration into adventitia and monocyte chemoattractant protein-1 (MCP-1) expression., Conclusion: These results suggest that MAPKs differentially regulate activation of adventitial fibroblast through GATA4/Cyclin D1 axis that participates in neointima formation., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

An aerobic, Gram-stain-negative, motile rod bacterium, designated as SYSU BS000021 T , was isolated from a black soil sample in Harbin, Heilongjiang province, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus Methylobacterium, and showed the highest sequence similarity to Methylobacterium segetis KCTC 62267  T (98.51%) and Methylobacterium oxalidis DSM 24028  T (97.79%). Growth occurred at 20-37℃ (optimum, 28 °C), pH 6.0-8.0 (optimum, pH 7.0) and in the presence of 0% (w/v) NaCl. Polar lipids comprised of phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one unidentified polar lipid. The major cellular fatty acids (> 5%) were C 18:0 and C 18:1 ω7c and/or C 18:1 ω6c. The predominant respiratory quinone was Q-10. The genomic G + C content was 68.36% based on the whole genome analysis. The average nucleotide identity (≤ 83.5%) and digital DNA-DNA hybridization (≤ 27.3%) values between strain SYSU BS000021 T and other members of the genus Methylobacterium were all lower than the threshold values recommended for distinguishing novel prokaryotic species. Based on the results of phenotypic, chemotaxonomic and phylogenetic analyses, strain SYSU BS000021 T represents a novel species of the genus Methylobacterium, for which the name Methylobacterium nigriterrae sp. nov. is proposed. The type strain of the proposed novel species is SYSU BS000021 T (= GDMCC 1.3814  T  = KCTC 8051  T )., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

High-performance electrochromic (EC) and electrofluorochromic (EFC) materials have garnered considerable interest due to their diverse applications in smart windows, optoelectronics, optical displays, military camouflage, etc. While many different EC and EFC polymers have been reported, their preparation often requires multiple steps, and their polymer molecular weights are subjected to batch variation. In this work, we prepared two triphenylamine (TPA)-based and two tetraphenylethylene (TPE)-based derivatives functionalized with terminal styryl groups via direct Suzuki coupling with (4-vinylphenyl)boronic acid and vinylboronic acid pinacol ester. The two novel TPE derivatives exhibited green-yellow aggregation-induced emission (AIE). The EC and EFC properties of pre- and post-thermally treated derivatives spin-coated onto ITO-glass substrates were studied. While all four derivatives showed modest absorption changes with applied voltages up to +2.4 V, retaining a high degree of optical transparency, they exhibited obvious EFC properties with the quenching of blue to yellow fluorescence with I OFF/ON contrast ratios of up to 7.0. The findings therefore demonstrate an elegant approach to preparing optically transparent, heat-induced, cross-linkable styryl-functionalized EFC systems.

The degradation of farmland in China underscores the need for developing and utilizing saline-alkali soil. Soil health relies on microbial activity, which aids in the restoration of the land's ecosystem, and hence it is important to understand microbial diversity. In the present study, two Gram-stain-positive strains HR 1-10 T and J-A-003 T were isolated from saline-alkali soil. Preliminary analysis suggested that these strains could be a novel species. Therefore, the taxonomic positions of these strains were evaluated using polyphasic analysis. Phylogenetic and 16S rRNA gene sequence analysis indicated that these strains should be assigned to the genus Halalkalibacter . Cell wall contained meso -2,6-diaminopimelic acid. The polar lipids present in both strains were diphosphatidyl-glycerol, phosphatidylglycerol, and an unidentified phospholipid. The major fatty acids (>10%) were anteiso-C 15:0 , C 16:0 and iso-C 15:0 . Average nucleotide identity and digital DNA#x2013;DNA hybridization values were below the threshold values (95% and 70%, respectively) for species delineation. Based on the above results, the strains represent two novel species of the genus Halalkalibacter , for which the names Halalkalibacter flavus sp. nov., and Halalkalibacter lacteus sp. nov., are proposed. The type strains are HR 1-10 T (=GDMCC 1.2946 T = MCCC 1K08312 T = JCM 36285 T ), and J-A-003 T (=GDMCC 1.2949 T = MCCC 1K08417 T = JCM 36286 T ).

Human organotypic bone models are an emerging technology that replicate bone physiology and mechanobiology for comprehensive in vitro experimentation over prolonged periods of time. Recently, we introduced a mineralized bone model based on 3D bioprinted cell-laden alginate-gelatin-graphene oxide hydrogels cultured under dynamic loading using commercially available human mesenchymal stem cells. In the present study, we created cell-laden scaffolds from primary human osteoblasts isolated from surgical waste material and investigated the effects of a previously reported optimal cell printing density (5 × 10 6 cells/mL bioink) vs. a higher physiological cell density (10 × 10 6 cells/mL bioink). We studied mineral formation, scaffold stiffness, and cell morphology over a 10-week period to determine culture conditions for primary human bone cells in this microenvironment. For analysis, the human bone-derived cell-laden scaffolds underwent multiscale assessment at specific timepoints. High cell viability was observed in both groups after bioprinting (>90%) and after 2 weeks of daily mechanical loading (>85%). Bioprinting at a higher cell density resulted in faster mineral formation rates, higher mineral densities and remarkably a 10-fold increase in stiffness compared to a modest 2-fold increase in the lower printing density group. In addition, physiological cell bioprinting densities positively impacted cell spreading and formation of dendritic interconnections. We conclude that our methodology of processing patient-specific human bone cells, subsequent biofabrication and dynamic culturing reliably affords mineralized cell-laden scaffolds. In the future, in vitro systems based on patient-derived cells could be applied to study the individual phenotype of bone disorders such as osteogenesis imperfecta and aid clinical decision making., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 de Leeuw, Graf, Lim, Zhang, Schädli, Peterhans, Rohrbach, Giunta, Rüger, Rubert and Müller.)

Background: Menarche is a substantial milestone of female puberty. Timing of age at menarche is considered the key to understanding the potential linkages with women's health outcomes later in life. This study aimed to explore the secular trends and urban‒rural disparities in the median age at menarche among Chinese Han girls from 1985 to 2019., Methods: Data were extracted from the 1985, 1995, 2005, 2014, and 2019 Chinese National Surveys on Students' Constitution and Health, which were nationally representative cross-sectional studies, and a total of 173,535 Han girls aged 9-18 years were examined. Girls were asked whether menarche had occurred. The median age at menarche was estimated by probit analysis. Z tests were used to compare the differences between survey years and between urban and rural areas., Results: The median age at menarche among Chinese Han girls decreased from 13.37 years in 1985 to 12.00 years in 2019, and the overall decrease was more significant in rural areas (1.77 years) than in urban areas (0.99 years). The average five-year change in the decrease in the median age at menarche showed an accelerating and then slowing pace; and it was observed similarly in both urban and rural areas. The urban‒rural disparities shrank from 0.64 years in 1985 to 0.44 years in 1995, then to 0.27 years in 2005, 0.24 years in 2014, and finally to - 0.14 years in 2019., Conclusions: The median age at menarche among Chinese Han girls continued to decline from 1985 to 2019 but at a slowing pace in the last five years. Urban‒rural disparities gradually narrowed. Sexual and reproductive health education and interventions to prevent the decline in the age of menarche are needed, especially in rural areas., (© 2023. Children's Hospital, Zhejiang University School of Medicine.)

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.)

Epithelial-mesenchymal transition (EMT) plays a critical role in hypertension-induced renal fibrosis, a final pathway that leads to end-stage renal failure. C-Atrial natriuretic peptide (ANP) 4-23 , a specific agonist of natriuretic peptide receptor-C (NPR-C), has been reported to have protective effects against hypertension. However, the role of C-ANP 4-23 in hypertension-associated renal fibrosis has not yet been elucidated. In this study, mice were randomly divided into SHAM group, DOCA-salt group and DOCA-salt + C-ANP 4-23 group. Renal morphology changes, renal function and fibrosis were detected. Human proximal tubular epithelial cells (HK2) stimulated by aldosterone were used for cell function and mechanism study. The DOCA-salt treated mice exhibited hypertension, kidney fibrosis and renal dysfunction, which were attenuated by C-ANP 4-23 . Moreover, C-ANP 4-23 inhibited DOCA-salt treatment-induced renal EMT as evidenced by decrease of the mesenchymal marker alpha-smooth muscle actin (ACTA2) and vimentin and increase of epithelial cell marker E-cadherin. In HK2 cells, aldosterone induced EMT response, which was also suppressed by C-ANP 4-23 . The key transcription factors (twist, snail, slug and ZEB1) involved in EMT were increased in the kidney of DOCA-salt-treated mice, which were also suppressed by C-ANP 4-23 . Mechanistically, C-ANP 4-23 inhibited the aldosterone-induced translocation of MR from cytosol to nucleus without change of MR expression. Furthermore, C-ANP 4-23 rescued the enhanced expression of NADPH oxidase (NOX) 4 and oxidative stress after aldosterone stimulation. Aldosterone-induced Akt and Erk1/2 activation was also suppressed by C-ANP 4-23 . Our data suggest that C-ANP 4-23 attenuates renal fibrosis, likely through inhibition of MR activation, enhanced oxidative stress and Akt and Erk1/2 signaling pathway., 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.)

This study compared the effects of Curcuma longa before and after processing with vinegar on the rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation to reveal the mechanism of vinegar processing in improving the role of C. longa in soothing liver and relieving pain. The rat model of dysmenorrhea with the syndrome of liver depression and Qi stagnation was established according to the Preparation of the Animal Model of Dysmenorrhea(Draft) and the chronic unpredictable stress me-thod. The changes in the body weight, organ indexes, writhing latency, writhing score, and serum levels of six liver function indicators, sex hormones, pain factors, and blood rheological indicators were measured to evaluate the efficacy of C. longa processed with vinegar or not in treating dysmenorrhea in the rats with syndrome of liver depression and qi stagnation. Compared with the model group, the C. longa group(processed with vinegar or not) showed slow weight loss, increase in writhing latency, and decrease in writhing response(P&lt;0.05). The inhibition rates on writhing in raw C. longa, vinegar-processed C. longa, and positive groups were 33.780%, 64.611%, and 62.466%, respectively. The significantly higher inhibition rate of the vinegar processing group indicated that vinegar-processed C. longa demonstrated more significant therapeutic effect. The vinegar-processed C. longa group showed lower levels of alanine aminotransferase(ALT), alkaline phosphatase(ALP), aspartate aminotransferase(AST), direct bilirubin(DBIL), and total bilirubin(TBIL) and higher level of albumin(ALB)(P&lt;0.05), which indicated that vinegar processing enhanced the therapeutic effect of C. longa on liver injury. The serum levels of estradiol(E&#95;2) and oxytocin(OT) were lower in the vinegar-processed C. longa group(P&lt;0.05), indicating that the vinegar-processed C. longa could regulate the sex hormone levels, reduce the activity of uterine smooth muscle and contraction of uterus, and alleviate the symptoms of dysmenorrhea in rats. Moreover, the vinegar-processed C. longa group showed lower interleukin-6(IL-6) and arginine vasopressin(AVP) levels and higher beta-endorphin(β-EP) level(P&lt;0.05), which indicated that vinegar-processed C. longa regulated the levels of pain factors to exert the pain-relieving effect. Drug intervention decreased the whole blood viscosity low-cut, medium-cut and high-cut values, plasma viscosity, whole blood reduction viscosity low-cut and high-cut values, erythrocyte cumulative pressure, and equation K value of erythrocyte sedimentation rate(P&lt;0.05), and the vinegar-processed C. longa group outperformed other groups. This result indicated that vinegar processing enhanced the function of C. longa in improving the local blood rheology. C. longa processed with vinegar can enter the liver to relieve the da-mage to the heart, liver, kidney, and uterus, repair the liver function, and recover the sex hormone levels and immune function by regulating the levels of sex hormones and pain factors and improving the blood rheology. It activates the pain-relieving mechanism to relieve the pain, protect the liver, and fight inflammation, which is consistent with the theory that vinegar processing facilitates C. longa entering the liver to sooth liver and relieve pain.

Background: Thalidomide is an effective treatment for refractory Crohn's disease (CD). However, thalidomide-induced peripheral neuropathy (TiPN), which has a large individual variation, is a major cause of treatment failure. TiPN is rarely predictable and recognized, especially in CD. It is necessary to develop a risk model to predict TiPN occurrence., Aim: To develop and compare a predictive model of TiPN using machine learning based on comprehensive clinical and genetic variables., Methods: A retrospective cohort of 164 CD patients from January 2016 to June 2022 was used to establish the model. The National Cancer Institute Common Toxicity Criteria Sensory Scale (version 4.0) was used to assess TiPN. With 18 clinical features and 150 genetic variables, five predictive models were established and evaluated by the confusion matrix receiver operating characteristic curve (AUROC), area under the precision-recall curve (AUPRC), specificity, sensitivity (recall rate), precision, accuracy, and F1 score., Results: The top-ranking five risk variables associated with TiPN were interleukin-12 rs1353248 [ P = 0.0004, odds ratio (OR): 8.983, 95% confidence interval (CI): 2.497-30.90], dose (mg/d, P = 0.002), brain-derived neurotrophic factor (BDNF) rs2030324 ( P = 0.001, OR: 3.164, 95%CI: 1.561-6.434), BDNF rs6265 ( P = 0.001, OR: 3.150, 95%CI: 1.546-6.073) and BDNF rs11030104 ( P = 0.001, OR: 3.091, 95%CI: 1.525-5.960). In the training set, gradient boosting decision tree (GBDT), extremely random trees (ET), random forest, logistic regression and extreme gradient boosting (XGBoost) obtained AUROC values > 0.90 and AUPRC > 0.87. Among these models, XGBoost and GBDT obtained the first two highest AUROC (0.90 and 1), AUPRC (0.98 and 1), accuracy (0.96 and 0.98), precision (0.90 and 0.95), F1 score (0.95 and 0.98), specificity (0.94 and 0.97), and sensitivity (1). In the validation set, XGBoost algorithm exhibited the best predictive performance with the highest specificity (0.857), accuracy (0.818), AUPRC (0.86) and AUROC (0.89). ET and GBDT obtained the highest sensitivity (1) and F1 score (0.8). Overall, compared with other state-of-the-art classifiers such as ET, GBDT and RF, XGBoost algorithm not only showed a more stable performance, but also yielded higher ROC-AUC and PRC-AUC scores, demonstrating its high accuracy in prediction of TiPN occurrence., Conclusion: The powerful XGBoost algorithm accurately predicts TiPN using 18 clinical features and 14 genetic variables. With the ability to identify high-risk patients using single nucleotide polymorphisms, it offers a feasible option for improving thalidomide efficacy in CD patients., Competing Interests: Conflict-of-interest statement: 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., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

Osteogenesis imperfecta (OI) is a heritable and chronically debilitating skeletal dysplasia. Patients with OI typically present with reduced bone mass, tendency for recurrent fractures, short stature and bowing deformities of the long bones. Mutations causative of OI have been identified in over 20 genes involved in collagen folding, posttranslational modification and processing, and in bone mineralization and osteoblast development. In 2016, we described the first X-linked recessive form of OI caused by MBTPS2 missense variants in patients with moderate to severe phenotypes. MBTPS2 encodes site-2 protease, a Golgi transmembrane protein that activates membrane-tethered transcription factors. These transcription factors regulate genes involved in lipid metabolism, bone and cartilage development, and ER stress response. The interpretation of genetic variants in MBTPS2 is complicated by the gene's pleiotropic properties; MBTPS2 variants can also cause the dermatological conditions Ichthyosis Follicularis, Atrichia and Photophobia (IFAP), Keratosis Follicularis Spinulosa Decalvans (KFSD) and Olmsted syndrome (OS) without skeletal abnormalities typical of OI. Using control and patient-derived fibroblasts, we previously identified gene expression signatures that distinguish MBTPS2 -OI from MBTPS2 -IFAP/KFSD and observed stronger suppression of genes involved in fatty acid metabolism in MBTPS2 -OI than in MBTPS2 -IFAP/KFSD; this was coupled with alterations in the relative abundance of fatty acids in MBTPS2 -OI. Furthermore, we observed a reduction in collagen deposition in the extracellular matrix by MBTPS2 -OI fibroblasts. Here, we extrapolate our observations in the molecular signature unique to MBTPS2 -OI to infer the pathogenicity of a novel MBTPS2 c.516A>C (p.Glu172Asp) variant of unknown significance in a male proband. The pregnancy was terminated at gestational week 21 after ultrasound scans showed bowing of femurs and tibiae and shortening of long bones particularly of the lower extremity; these were further confirmed by autopsy. By performing transcriptional analyses, gas chromatography-tandem mass spectrometry-based quantification of fatty acids and immunocytochemistry on fibroblasts derived from the umbilical cord of the proband, we observed perturbations in fatty acid metabolism and collagen production similar to what we previously described in MBTPS2 -OI. These findings support pathogenicity of the MBTPS2 variant p.Glu172Asp as OI-causative and highlights the value of extrapolating molecular signatures identified in multiomics studies to characterize novel genetic variants., 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 Lim, Marcionelli, Srikanthan, Ndarugendamwo, Pinner, Rohrbach and Giunta.)

The elderly have higher concentrations of advanced glycation end-products (AGEs). AGEs are considered risk factors that accelerate aging and cause diabetic nephropathy. The effects of AGEs on renal function in the elderly remain to be clarified. This study aimed to explore the role of AGEs in renal function decline in the elderly and the protective effect of resveratrol, a stilbenoid polyphenol, comparing it with aminoguanidine (an AGEs inhibitor). A D-galactose-induced aging mouse model was used to explore the role of AGEs in the process of renal aging. The mice were administered D-galactose subcutaneously for eight weeks in the presence or absence of orally administered aminoguanidine or resveratrol. The results showed that the serum levels of AGEs and renal function markers BUN, creatinine, and cystatin C in the mice significantly increased after the administration of D-galactose, and this outcome could be significantly reversed by treatment with aminoguanidine or resveratrol. The protein expression levels for apoptosis, fibrosis, and aging-related indicators in the kidneys were significantly increased, which could also be reversed by treatment with aminoguanidine or resveratrol. These findings suggest that resveratrol could alleviate AGEs-related renal dysfunction through the improvement of renal cellular senescence, apoptosis, and fibrosis in D-galactose-induced aging in mice.

The liver plays a protective role in myocardial infarction (MI). However, very little is known about the mechanisms. Here, we identify mineralocorticoid receptor (MR) as a pivotal nexus that conveys communications between the liver and the heart during MI. Hepatocyte MR deficiency and MR antagonist spironolactone both improve cardiac repair after MI through regulation on hepatic fibroblast growth factor 21 (FGF21), illustrating an MR/FGF21 axis that underlies the liver-to-heart protection against MI. In addition, an upstreaming acute interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) pathway transmits the heart-to-liver signal to suppress MR expression after MI. Hepatocyte Il6 receptor deficiency and Stat3 deficiency both aggravate cardiac injury through their regulation on the MR/FGF21 axis. Therefore, we have unveiled an IL-6/STAT3/MR/FGF21 signaling axis that mediates heart-liver cross-talk during MI. Targeting the signaling axis and the cross-talk could provide new strategies to treat MI and heart failure.

Objectives: The aim of this study was to investigate the clinical characteristics of renal artery fibromuscular dysplasia (FMD) in patients in China and identify the cure rate of hypertension after angioplasty., Methods: Consecutive hypertensive patients with renal artery stenosis caused by FMD who underwent catheter-based angiography, and were followed at two Chinese referral centres, were retrospectively analysed. All patients underwent a detailed investigation, including demographic characteristics, clinical characteristics, biochemical sampling, Doppler ultrasonography of carotid arteries, magnetic resonance angiography (MRA) of the intracranial artery, and CTA or MRA of the abdominal artery and catheter-based renal angiography. Patients were routinely followed up at 1 month, 6 months and every year after the procedure., Results: Among 245 study participants, with a mean diagnosed age of 26.9 ± 9.9 years, 137 (55.9%) were women, and 38 (15.5%) were children. All patients were diagnosed with hypertension at a mean age of 23.4 ± 8.4 years. There were 73.5% focal and 15.2% multivessel cases. Aneurysms, arterial dissections and total occlusions were found in 21.6, 4.1 and 12.2% of patients, respectively. Patients with multifocal FMD were older (26.0 vs. 23.7 years, P  = 0.021) and more often female (70.8 vs. 50.6%, P  = 0.004). Among children with renal FMD, 55.2% were men, and 86.8% were focal. After a median follow-up of 7.0 years, multifocal FMD had a higher cure rate of hypertension than focal FMD after revascularization (71.7 vs. 55.8%, P  = 0.032)., Conclusion: In a cohort of mostly young Chinese patients, the prevalence of hypertension associated with renal FMD is similar in both sexes. Focal FMDs were more frequent than the multifocal ones and, after angioplasty, were associated with a worse blood pressure outcome., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Complement activation is thought to underline the pathologic progression of obesity-related metabolic disorders; however, its role in adaptive thermogenesis has scarcely been explored. Here, we identify complement C3a receptor (C3aR) and C5a receptor (C5aR) as critical switches to control adipocyte browning and energy balance in male mice. Loss of C3aR and C5aR in combination, more than individually, increases cold-induced adipocyte browning and attenuates diet-induced obesity in male mice. Mechanistically, loss of C3aR and C5aR increases regulatory T cell (Treg) accumulation in the subcutaneous white adipose tissue during cold exposure or high-fat diet. Activated Tregs produce adenosine, which is converted to inosine by adipocyte-derived adenosine deaminases. Inosine promotes adipocyte browning in a manner dependent on activating adenosine A2a receptor. These data reveal a regulatory mechanism of complement in controlling adaptive thermogenesis and suggest that targeting the C3aR/C5aR pathways may represent a therapeutic strategy in treating obesity-related metabolic diseases., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Rational cropping maintains high soil fertility and a healthy ecosystem. Soil microorganism is the controller of soil fertility. Meanwhile, soil microbial communities also respond to different cropping patterns. The mechanisms by which biotic and abiotic factors were affected by different cropping sequences remain unclear in the major grain-producing regions of northeastern China. To evaluate the effects of different cropping sequences under conventional fertilization practices on soil properties, microbial communities, and crop yield, six types of plant cropping systems were performed, including soybean monoculture, wheat-soybean rotation, wheat-maize-soybean rotation, soybean-maize-maize rotation, maize-soybean-soybean rotation and maize monoculture. Our results showed that compared with the single cropping system, soybean and maize crop rotation in different combinations or sequences can increase soil total organic carbon and nutrients, and promote soybean and maize yield, especially using soybean-maize-maize and maize-soybean-soybean planting system. The 16S rRNA and internal transcribed spacer (ITS) amplicon sequencing showed that different cropping systems had different effects on bacterial and fungal communities. The bacterial and fungal communities of soybean monoculture were less diverse when compared to the other crop rotation planting system. Among the different cropping sequences, the number of observed bacterial species was greater in soybean-maize-maize planting setup and fungal species in maize-soybean-soybean planting setup. Some dominant and functional bacterial and fungal taxa in the rotation soils were observed. Network-based analysis suggests that bacterial phyla Acidobacteria and Actinobacteria while fungal phylum Ascomycota showed a positive correlation with other microbial communities. The phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) result showed the presence of various metabolic pathways. Besides, the soybean-maize-maize significantly increased the proportion of some beneficial microorganisms in the soil and reduced the soil-borne animal and plant pathogens. These results warrant further investigation into the mechanisms driving responses of beneficial microbial communities and their capacity on improving soil fertility during legume cropping. The present study extends our understanding of how different crop rotations effect soil parameters, microbial diversity, and metabolic functions, and reveals the importance of crop rotation sequences. These findings could be used to guide decision-making from the microbial perspective for annual crop planting and soil management approaches., 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 Sun, Wang, Narsing Rao, Shi, Lian, Jin, Wang, Li, Wang, Banerjee, Cui and Wei.)

Background: Crohn's disease (CD), often occurring in women of child-bearing age, can decline the fertility rate. However, whether it reduces ovarian reserve has been rarely reported. This study aimed to evaluate the ovarian reserve in women with CD from the perspective of anti-Müllerian hormone (AMH), and explore the factors that can decrease ovarian reserve., Methods: A case-control retrospective study was designed. We analyzed the AMH levels in a total of 135 CD women and 878 healthy controls. Through propensity score matching, the subjects were assigned in a ratio of 1:3 to CD group (n = 121) and control group (n = 324). Both groups shared similar basic characteristics, like age, body mass index and smoking status. Serum AMH levels were measured by chemiluminescence., Results: The AMH level in the CD group was significantly lower than that in the control group (2.17 ± 2.23 μg/L vs 3.95 ± 2.01 μg/L, 95%CI [1.34-2.21], P < 0.001). In both groups, the AMH levels decreased as age increased, but without between-group difference in the decreasing rate (P = 0.639). Multivariate analysis showed that age > 30 years (OR, 2.905; 95%CI [1.053-8.531], P = 0.017), disease activity (OR,4.314; 95%CI [1.561-12.910], P = 0.002) and thalidomide use (OR,12.628; 95%CI [4.351 -42.820], P < 0.001) were independent risk factors associated with decreased ovarian reserve (AMH<1.1μg/L)., Conclusion: Ovarian reserve is lower in CD women than in healthy women. Age, CD activity and medication of thalidomide are risk factors that can aggravate the decline of ovarian reserve., (© 2023. The Author(s).)

Low-temperature fuel cells have great application potential in electric vehicles and portable electronic devices, which need advanced electrocatalysts. Controlling the composition and morphology of electrocatalysts can effectively improve their catalytic performance. In this work, a Rh metallene (Rhlene)-supported Pt nanoparticle (Pt/Rhlene) electrocatalyst is successfully synthesized by a simple chemical reduction method, in which ultra-small Pt nanoparticles are uniformly attached to the Rhlene surface due to the high surface area of Rhlene. Pt/Rhlene reveals a 3.60-fold Pt-mass activity enhancement for the ethylene glycol oxidation reaction in alkaline solution compared with commercial Pt black, and maintains high stability and excellent poisoning-tolerance during electrocatalysis, owing to the specific physical/chemical properties of Rhlene. The superior electrocatalytic performance of Pt/Rhlene may open an avenue to synthesize other metallene-supported noble metal nanoparticle hybrids for various electrocatalytic applications.

Objectives: Xerostomia is a subjective sensation of dry mouth associated with many medications and increases the risk of tooth decay and other oral complications. The aim of this study was to identify unreported medications associated with dry mouth from the Australian Database of Adverse Event Notifications (ADAEN) from the Therapeutic Goods Administration (TGA) in Australia., Methods: This was a descriptive retrospective study. A request was made to the TGA to provide all reports associated with dry mouth. De-identified reports were provided from the commencement of the database in 1971 until June 2020. Drugs were divided into established drugs that are associated with xerostomia in the primary literature and secondary drugs not reported in the primary literature., Key Findings: There were 1927 individual case reports for dry mouth associated with medications. Of these, there were 1379 reports of established (primary) drugs and 1481 reports of secondary drugs associated with xerostomia. Dry mouth was found to be associated with many medication classes; analgesics, cardiovascular and gastrointestinal drugs had the greatest number of secondary drugs reported., Conclusions: A comprehensive list of suspected medications associated with xerostomia has been established. This adds to the growing catalogue of medications associated with dry mouth, where several medications have not previously been identified in the primary literature., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Royal Pharmaceutical Society.)

Thiopurine dose optimization by thiopurine-S-methyltransferase (TPMT) or nudix hydrolase-15 (NUDT15) significantly reduced early leucopenia in Asia. However, it fails to avoid the late incidence (> 2 months). Although laboratory monitoring of 6-thioguanine nucleotides (6TGN) to optimize thiopurine dose was suggested in White patients the exact association between leucopenia and 6TGN was controversial in Asian patients. In the present study, we aimed to explore whether DNA-thioguanine nucleotides (DNA-TGs) in leukocytes, compared with 6TGN in erythrocytes, can be a better biomarker for late leucopenia. This was a prospective, observational study. Patients with inflammatory bowel disease (IBD) prescribed thiopurine from February 2019 to December 2019 were recruited. Thiopurine dose was optimized by NUDT15 C415T (rs116855232). DNA-TG and 6TGN levels were determined at the time of late leucopenia or 2 months after the stable dose was obtained. A total of 308 patients were included. Thiopurine induced late leucopenia (white blood cells < 3.5 × 10 9 /L) were observed in 43 patients (14.0%), who had significantly higher DNA-TG concentration than those without leucopenia (P = 4.1 × 10 -9 , 423.3 (~ 342.2 to 565.7) vs. 270.5 (~ 188.1 to 394.3) fmol/μg DNA). No difference in 6TGN concentrations between leucopenia and non-leucopenia was found. With a DNA-TG threshold of 340.1 fmol/μg DNA, 83.7% of leucopenia cases could be identified. Multivariate analysis showed that DNA-TG was an independent risk factor for late leucopenia. Quantification of DNA-TG, rather than 6TGN, can be applied to gauge thiopurine therapy after NUDT15 screening in Chinese patients with IBD., (© 2022 The Authors. Clinical Pharmacology & Therapeutics © 2022 American Society for Clinical Pharmacology and Therapeutics.)

Background: Thalidomide is applied in therapy for refractory Crohn's disease (CD) in adults, but systematic and rigorous clinical evidence is scant. The aim was to provide theoretical references for the efficacy of thalidomide in the therapy for refractory CD in adults., Methods: A double-center, double-blind, placebo-controlled, randomized clinical trial of refractory CD in adults in two inflammatory bowel disease centers in China. In the double-blind trial, patients were randomly assigned to 100 mg of thalidomide or placebo daily for 8 weeks. The primary outcome was considered as the clinical remission rate calculated based on the Crohn's disease activity index at the eighth week following thalidomide or placebo treatment. In open label, non-response to placebo was additionally treated with 8 weeks of thalidomide; all responders were continuously treated with thalidomide until the 48th week., Results: Twenty-five patients were randomly assigned to each group. At the eighth week, the clinical remission rate in the thalidomide group was significantly higher than that in the placebo group (68.0% [17/25] vs 16.0% [4/25]; relative risk, 4.2; 95% confidence interval, 1.8-10.9, P  <   0.001). After a 48-week follow-up, the continuous treatment rate of thalidomide was 46.3% (19/41). Adverse events during the whole process were reported in 58.5% of patients, mainly involving drowsiness, rash, and peripheral neuropathy that were mild and tolerable., Conclusion: Thalidomide can be used in the induction and maintenance therapy of refractory CD in adults. And it could be one of the treatment options for refractory CD., (© The Author(s) 2022. Published by Oxford University Press and Sixth Affiliated Hospital of Sun Yat-sen University.)

The recognition-directed host-guest interaction is recognized as a valuable tool for creating supramolecular polymers. Functional hydrogels constructed through the dynamic and reversible host-guest complexation are endowed with a great many appealing features, such as superior self-healing, injectability, flexibility, stimuli-responsiveness and biocompatibility, which are crucial for biological and medicinal applications. With numerous topological structures and host-guest combinations established previously, recent breakthroughs in this area mostly focus on further improvement and fine-tuning of various properties for practical utilizations. The current contribution provides a comprehensive overview of the latest developments in host-guest supramolecular hydrogels, with a particular emphasis on the innovative molecular-level design strategies and hydrogel formation methodologies targeting at a wide range of active biomedical domains, including drug delivery, 3D printing, wound healing, tissue engineering, artificial actuators, biosensors, etc. Furthermore, a brief conclusion and discussion on the steps forward to bring these smart hydrogels to clinical practice is also presented., (© 2022 Wiley-VCH GmbH.)

Long non-coding RNAs (lncRNAs) can influence the proliferation, autophagy, and apoptosis of non-small cell lung cancer (NSCLC). LncRNAs also emerge as valuable prognostic factors for NSCLC patients. Consequently, we set out to discover more autophagy-associated lncRNAs. We acquired autophagy-associated genes and information on lncRNAs from The Cancer Genome Atlas database (TCGA), and the Human Autophagy Database (HADb). Then, the prognostic prediction signature was constructed through using co-expression and Cox regression analysis. The signature was constructed including 7 autophagy-associated lncRNAs (ABALON, NKILA, LINC00941, AL161431.1, AL691432.2, AC020765.2, MMP2-AS1). After that, we used univariate and multivariate Cox regression analysis to calculate the risk score. The survival analysis and ROC curve analysis confirmed good performances of the signature. GSEA indicated that the high-risk group was principally enriched in the adherens junction pathway. In addition, biological experiments showed that ABALON promoted the proliferation, metastasis and autophagy levels of NSCLC cells. These findings demonstrate that the risk signature consisting of 7 autophagy-associated lncRNAs accurately predicts the prognosis of NSCLC patients and should be investigated for potential therapeutic targets in clinic., 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 © 2022 Hu, Zhang, Zhang, Chen, Cao, Yu and Ge.)

Nanophotonics relies on precise control of refractive index (RI) which can be designed with metamaterials. Plasmonic superstructures of nanoparticles (NPs) can suggest a versatile way of tuning RI. However, the plasmonic effects in the superstructures demand 1 nm-level exquisite control over the interparticle gap, which is challenging in a sub-wavelength NPs. Thus far, a large-area demonstration has been mostly discouraged. Here, heteroligand AuNPs are prepared, which are stable in oil but become Janus particles at the oil-water interface, called "adaptive Janus particles." NPs are bound at the interface and assembled into 2D arrays over square centimeters as toluene evaporates, which distinctively exhibits the RI tunability. In visible and NIR light, the 2D superstructures exhibit the highest-ever RI (≈7.8) with varying the size and interparticle gap of NPs, which is successfully explained by a plasmonic percolation model. Furthermore, fully solution-processable 2D plasmonic superstructures are proved to be advantageous in flexible photonic devices such as distributed Bragg reflectors., (© 2022 Wiley-VCH GmbH.)

A novel bacterium, designated strain APA&#95;H-1(4) T , was isolated from the saline-alkaline soil, Zhaodong, Heilongjiang Province, China. Phenotypic and chemotaxonomic analyses, and whole-genome sequencing were used to determine the taxonomic position of the strain. Phylogenetic analysis indicated that the isolate belongs to the genus Oceanobacillus, and showed the highest sequence similarity to O. damuensis KCTC 33146 T (98.35%, similarity) and 'O. massiliensis' DSM 24644 (98.32%). The average nucleotide identity values between strain APA&#95;H-1(4) T and other members of the genus Oceanobacillus were lower than 82% recommended for distinguishing novel prokaryotic species. The digital DNA-DNA hybridization values of strain APA&#95;H-1(4) T with O. damuensis KCTC 33146 T and 'O. massiliensis' DSM 24644 were 13.60 and 17.60%, respectively. Cells of strain APA&#95;H-1(4) T were Gram-staining positive, motile, aerobic, spore-forming rods (0.5-0.7 × 1.8-2.6 μm) with flagella. The growth was found to occur optimally at 37 °C. The whole-cell hydrolysate contained meso-diaminopimelic acid as the diagnostic cell wall diamino acid. The main detected polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified polar lipid. The predominant respiratory quinone was identified as menaquinone-7 (MK-7). The major cellular fatty acid (>10%) was anteiso-C 15:0 . The G + C content of the genomic DNA was determined to be 38.4% based on the draft genome sequence. Based on the comparative analysis of polyphasic taxonomic data, strain APA&#95;H-1(4) T represents a novel species of the genus Oceanobacillus, for which the name Oceanobacillus saliphilus sp. nov. is proposed. The type strain is APA&#95;H-1(4) T (=GDMCC 1.2239 T  = KCTC 43254 T )., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There are few studies on the severity and prognosis of patients infected with the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) omicron variant. From January 11, 2022 to January 25, 2022, 181 patients were infected with the SARS-CoV-2 omicron variant in a single hospital in Korea. The initial clinical characteristics were investigated through the COVID-19 basic investigation form. Outcomes were reviewed using medical records. The median age of the patients was 57 years (range 1-90), and 95 patients (52.5%) were male. None were re-infected with SARS-CoV-2, and 127 (70.2%) were fully vaccinated (boosted or within 6 months after second vaccination). Forty-two patients (23.2%) were asymptomatic. Among symptomatic patients, the frequency of symptoms was as follows: cough (37.0%), sore throat (33.7%), and fever (30.4%). In terms of disease severity, 168 (92.8%) patients did not require supplemental oxygen, 6 (3.3%) required low-flow oxygen, 5 (2.8%) required high-flow oxygen, and 2 (1.1%) died. Four of the five individuals who required high-flow oxygen and the two who died were not vaccinated. Most of the patients who contracted the SARS-CoV-2 omicron variant exhibited mild clinical features; however, severe clinical features including mortality were encountered among individuals who were not vaccinated., Competing Interests: The authors have no potential conflicts of interest to disclose., (© Copyright: Yonsei University College of Medicine 2022.)

Background: The ADRB3 (β3-adrenergic receptors), which is predominantly expressed in brown adipose tissue (BAT), can activate BAT and improve metabolic health. Previous studies indicate that the endocrine function of BAT is associated with cardiac homeostasis and diseases. Here, we investigate the role of ADRB3 activation-mediated BAT function in cardiac remodeling., Methods: BKO (brown adipocyte-specific ADRB3 knockout) and littermate control mice were subjected to Ang II (angiotensin II) for 28 days. Exosomes from ADRB3 antagonist SR59230A (SR-exo) or agonist mirabegron (MR-exo) treated brown adipocytes were intravenously injected to Ang II-infused mice., Results: BKO markedly accelerated cardiac hypertrophy and fibrosis compared with control mice after Ang II infusion. In vitro, ADRB3 KO rather than control brown adipocytes aggravated expression of fibrotic genes in cardiac fibroblasts, and this difference was not detected after exosome inhibitor treatment. Consistently, BKO brown adipocyte-derived exosomes accelerated Ang II-induced cardiac fibroblast dysfunction compared with control exosomes. Furthermore, SR-exo significantly aggravated Ang II-induced cardiac remodeling, whereas MR-exo attenuated cardiac dysfunction. Mechanistically, ADRB3 KO or SR59230A treatment in brown adipocytes resulted an increase of iNOS (inducible nitric oxide synthase) in exosomes. Knockdown of iNOS in brown adipocytes reversed SR-exo-aggravated cardiac remodeling., Conclusions: Our data illustrated a new endocrine pattern of BAT in regulating cardiac remodeling, suggesting that activation of ADRB3 in brown adipocytes offers cardiac protection through suppressing exosomal iNOS.

Purpose: To evaluate the trueness of one stationary and two mobile systems for 3D facial scanning., Materials and Methods: Twenty participants were included in this study. After marking facial soft tissue landmarks, their faces were scanned using three facial scanning systems: the Bellus3D Dental Pro app on an iPad Pro 2020 (Apple; IP); the ARC-7 Face Scanning System (Bellus3D; BA); and the EinScan Pro 2X Plus (Shining 3D Tech; EP) following the manufacturers' operating instructions. Three-dimensional images were reconstructed with corresponding software and saved in object (OBJ) file format. The interlandmark distances were measured and compared to direct caliper measurements, and absolute error (AE) was chosen as the measurement to determine the trueness of the three scanners. The normal distribution and variance of homogeneity were measured, and then the data were analyzed using one-way ANOVA or Kruskal-Wallis H test. The significance level was set at P = .05., Results: For the measurement of interlandmark distances, no significant differences were found among the four measuring techniques, and the mean AEs of the IP, BA, and EP systems were 1.17 ± 0.80 mm, 0.76 ± 0.61 mm, and 0.69 ± 0.65 mm., Conclusion: The three facial scanning systems tested provided a reliable 3D facial reconstruction. The portable IP system could meet the clinical requirements for facial scanning, but it is suggested to select the EP and BA systems when a higher trueness is required.

Background: Adrenal venous sampling (AVS) is recognized as the gold standard for subtyping primary aldosteronism (PA), but its invasive nature and technical challenges limit its availability. A recent study reported that sodium chloride cotransporter (NCC) in urinary extracellular vesicles (uEVs) is a promising marker for assessing the biological activity of aldosterone and can be treated as a potential biomarker of PA. The current study was conducted to verify the hypothesis that the expression of NCC and its phosphorylated form (pNCC) in uEVs are different in various subtypes and genotypes of PA and can be used to select AVS candidates., Methods: A total of 50 patients with PA were enrolled in the study. Urinary extracellular vesicles (uEVs) were isolated from spot urine samples using ultracentrifugation. NCC and pNCC expressions were tested in patients diagnosed with PA who underwent AVS. Sanger sequencing of KCNJ5 was performed on DNA extracted from adrenal adenoma., Results: pNCC (1.89 folds, P <.0001) and NCC (1.82 folds, P =0.0002) was more abundant in the uEVs in the high lateralization index (h-LI, ≥ 4) group than in the low LI (l-LI, < 4) group. Carriers of the somatic KCNJ5 mutations, compared with non-carriers, had more abundant pNCC expression (2.16 folds, P=0.0039). Positive correlation between pNCC abundance and plasma aldosterone level was found in this study (R = 0.1220, P = 0.0129)., Conclusions: The expression of pNCC in uEVs in patients with PA with various subtypes and genotypes was different. It can be used as biomarker of AVS for PA subtyping., 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 © 2022 Kong, Tang, Kang, Dong, Tong, Xu, Gao, Wang, Shen and Zhu.)

Purpose: To evaluate the teaching effect of making custom trays via CAD in dental postgraduates., Methods: Twenty-seven dental postgraduates from first to third grade at the School and Hospital of Stomatology, Tongji University, Shanghai were given an informed consent to explain and request participation in the study. First, a lecture about the theory and process of fabricating custom tray via traditional hand-made method and CAD technique was given, then the students fabricated custom trays via the two methods and completed an online survey. The working time, margin extension and students' preference were analyzed with SPSS 22.0 software package., Results: The working time was shorter, the margin extension was superior, and students' preference was higher via CAD than traditional method, the difference was significant(P＜0.05)., Conclusions: CAD is more conducive to enhance students' understanding of custom tray manufacturing process and relevant theoretical knowledge. It is recommended to integrate digital technology into dental curriculum.

Kombucha is a traditional beverage of Manchurian origin, typically made by fermenting sugared black or green tea with the symbiotic consortium of bacteria and yeast (SCOBY). The beverage has gained increasing popularity in recent years, mainly due to its heralded health benefits. The fermentation process of kombucha also results in the production of various bioactive compounds with antimicrobial potential, making it a promising candidate in the exploration of alternative sources of antimicrobial agents, and may be helpful in combating the rising threat of antibiotic resistance. Literature survey performed on Web of Science, Scopus, and PubMed revealed the extensive research that has firmly established the antimicrobial activity of kombucha against a broad spectrum of bacteria and fungi. This activity could be attributed to the synergistic activities of the microbial species in the kombucha microbiota that led to the synthesis of compounds with antimicrobial properties such as acetic acid and various polyphenols. However, research thus far only involved screening for the antimicrobial activity of kombucha. Therefore, there is still a research gap about the molecular mechanism of the kombucha reaction against specific pathogens and its influence on human health upon consumption. Future research may focus on investigating this aspect. Further characterization of the biological activity of the microbial community in kombucha may also facilitate the discovery of novel antimicrobial compounds, such as bacteriocins produced by the microorganisms., (© 2022 Institute of Food Technologists®.)

Background: Tanning is an important physiological process with critical roles in cuticle pigmentation and sclerotization. Previous studies have shown that insect cuticle tanning is closely associated with the tyrosine metabolism pathway, which consists of a series of enzymes., Results: In this study, 24 tyrosine metabolism pathway genes were identified in the oriental fruit fly Bactrocera dorsalis (Hendel) genome. Gene expression profiles throughout 15 developmental stages of B. dorsalis were established based on our previous RNA sequencing data, and we found that 13 enzyme genes could be involved in the process of pupariation. Accordingly, a tyrosine-mediated tanning pathway during the pupariation of B. dorsalis was predicted and a critical enzyme, 3,4-dihydroxyphenylalanine (DOPA) decarboxylase (DDC), was used to explore its possible roles in formation of the puparium. First, a real-time quantitative polymerase chain reaction confirmed that BdDDC had an epidermis-specific expression pattern, and was highly expressed during larval metamorphosis in B. dorsalis. Subsequent disruption of BdDDC by feeding 5-day-old larvae with DDC inhibitor (l-α-methyl-DOPA) could lead to: (i) a significant decrease in BdDDC enzyme activity and dopamine concentration; (ii) defects in puparium pigmentation; (iii) impairment of the morphology and less thickness of the puparium; and (iv) lower pupal weight and obstacles to eclosion., Conclusion: This study provided a potential tyrosine metabolic pathway that was responsible for insect tanning during pupariation, and the BdDDC enzyme has been shown to have crucial roles in larval-pupal tanning of B. dorsalis. © 2021 Society of Chemical Industry., (© 2021 Society of Chemical Industry.)

A Gram-positive strain APA H-16(1) T was isolated from a saline-alkali soil sample collected from Heilongjiang Province, China. Cells were rod shaped, non-motile, endospore forming, and aerobic. Growth occurred at 10-45 °C (optimum, 35 °C), pH 7.0-10.5 (optimum, pH 9.5), and could tolerate NaCl up to 15.0% (w/v). Strain showed low 16S rRNA gene sequence similarities with Alteribacter natronophilus (97.8%), Alteribacter aurantiacus (97.7%), and Alteribacter populi (97.1%). The cell wall peptidoglycan was meso-diaminopimelic acid. The predominant menaquinone was MK-7. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, unidentified aminophospholipids, unidentified phospholipid, and unidentified lipid. The major fatty acids were anteiso-C 15:0 , and iso-C 15:0 . The genomic G + C content was 45.1%. The average nucleotide identity and digital DNA-DNA hybridization values between strain APA H-16(1) T and the most closely related species were below the cut-off level (95-96%; 70%) for species delineation. Based on phenotypic, phylogenetic, chemotaxonomic, and genome comparison, strain APA H-16(1) T represents a novel species of the genus Alteribacter, for which the name Alteribacter salitolerans sp. nov. is proposed. The type strain is APA H-16(1) T (= KCTC 43228 T  = CICC 25092 T )., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Pre-metastatic niche formation is critical for the colonization of disseminated cancer cells in distant organs. Here we find that lung mesenchymal stromal cells (LMSCs) at pre-metastatic stage possess potent metastasis-promoting activity. RNA-seq reveals an upregulation of complement 3 (C3) in those LMSCs. C3 is found to promote neutrophil recruitment and the formation of neutrophil extracellular traps (NETs), which facilitate cancer cell metastasis to the lungs. C3 expression in LMSCs is induced and sustained by Th2 cytokines in a STAT6-dependent manner. LMSCs-driven lung metastasis is abolished in Th1-skewing Stat6-deficient mice. Blockade of IL-4 by antibody also attenuates LMSCs-driven cancer metastasis to the lungs. Consistently, metastasis is greatly enhanced in Th2-skewing T-bet-deficient mice or in nude mice adoptively transferred with T-bet-deficient T cells. Increased C3 levels are also detected in breast cancer patients. Our results suggest that targeting the Th2-STAT6-C3-NETs cascade may reduce breast cancer metastasis to the lungs., (© 2021. The Author(s).)

The nitrate electroreduction reaction (NO 3 - -ERR) is an efficient and green approach for nitrate remediation, which requires a highly active and selective electrocatalyst. In this work, porous and amorphous cobalt phosphide nanoshuttles (CoP PANSs) are successfully synthesized by using Mg 2+ ion-doped calcium carbonate nanoshuttles (Mg-CaCO 3 NSs) as the initial reaction precursor via precipitation transformation and a high-temperature phosphidation strategy. Various physical characterizations show that CoP PANSs have porous architecture, amorphous crystal structure, and big surface area. Electrochemical measurements reveal for the first time that CoP PANSs have outstanding electroactivity for NO 3 - -ERR in a neutral electrolyte. At an applied potential of -0.5 V vs reversible hydrogen electrode, CoP PANSs can achieve a high Faraday efficiency (94.24 ± 2.8%) and high yield rate (19.28 ± 0.53 mg h -1 mg cat -1 ) for ammonia production, which exceeds most reported values at various electrocatalysts for NO 3 - -ERR. Thus, the present result indicates that cobalt phosphide nanomaterials have promising application for NO 3 - -ERR.

Obesity-induced secretory disorder of adipose tissue-derived factors is important for cardiac damage. However, whether platelet-derived growth factor-D (PDGF-D), a newly identified adipokine, regulates cardiac remodeling in angiotensin II (AngII)-infused obese mice is unclear. Here, we found obesity induced PDGF-D expression in adipose tissue as well as more severe cardiac remodeling compared with control lean mice after AngII infusion. Adipocyte-specific PDGF-D knockout attenuated hypertensive cardiac remodeling in obese mice. Consistently, adipocyte-specific PDGF-D overexpression transgenic mice (PA-Tg) showed exacerbated cardiac remodeling after AngII infusion without high-fat diet treatment. Mechanistic studies indicated that AngII-stimulated macrophages produce urokinase plasminogen activator (uPA) that activates PDGF-D by splicing full-length PDGF-D into the active PDGF-DD. Moreover, bone marrow-specific uPA knockdown decreased active PDGF-DD levels in the heart and improved cardiac remodeling in HFD hypertensive mice. Together, our data provide for the first time a new interaction pattern between macrophage and adipocyte: that macrophage-derived uPA activates adipocyte-secreted PDGF-D, which finally accelerates AngII-induced cardiac remodeling in obese mice., Competing Interests: Disclosures: The authors declare no competing interests exist., (© 2021 Cheng et al.)

Background: In Taiwan, the Chiayi City Government and Industrial Development Bureau of the Ministry of Economic Affairs have worked together to promote smart health management in the community and encourage people to use the intelligent physical health measurement system (IPHMS) with Smart Body Health Measuring Machine. Volunteers help participants in the community to use the IPHMS to ensure that measurements are taken correctly., Objectives: This study aimed to explore volunteers' satisfaction with using the IPHMS and the effects of the measurement service on the participants' measurement behavior intention, and further explore the impact on their active aging., Methods: This study used a paper questionnaire to survey both the participants of the measurement service and the community volunteers from March to April 2021. A total of 180 valid responses were collected., Results: The sociodemographic information showed that the volunteers were mostly female, were aged over 61 years old, had received junior college education, had spent less than 3-6 years in community service, and had 6 months to 1 year of measured service experience. Additionally, the participants of the measurement service were mostly female, were aged over 61 years old, had received below middle school education, had spent less than 1-3 years in community service, and spent an average of 5 days in the community each week. Our results showed that the information quality (β = 0.352, p < 0.001) and system quality (β = 0.701, p < 0.001) had significant effects on volunteers' satisfaction of using the IPHMS. Subjective norms had significant effects on participants' perceived disease threat (β = 0.347, p < 0.001) and behavior intention of management service (β = 0.701, p < 0.001); furthermore, behavior intention had significant effects on their social participation for active aging (β = 0.430, p < 0.05)., Conclusions: Improving the system and information quality is likely to improve volunteers' satisfaction with the system. Active aging factors only affect social participation, which represents the measurement services promote for social interaction mostly.

Background Adventitial remodeling is a pathological hallmark of hypertension that results in target organ damage. Activated adventitial fibroblasts have emerged as critical regulators in this process, but the precise mechanism remains unclear. Methods and Results Interleukin 11 (IL-11) knockout and wild-type mice were subjected to angiotensin II (Ang II) infusion to establish models of hypertension-associated vascular remodeling. IL-11 mRNA and protein were increased especially in the adventitia in response to Ang II. Compared with wild-type mice, Ang II-treated IL-11 knockout mice showed amelioration of vascular hypertrophy, adventitial fibrosis, macrophage infiltration, and inflammatory factor expression. Recombination mouse IL-11 exacerbated adventitial fibrosis in Ang II-infused wild-type mice. Interestingly, IL-11 neutralizing antibody attenuated adventitial fibrosis, macrophage infiltration, and inflammatory factor expression after Ang II infusion for 7 days. Mechanistically, in primary cultured adventitial fibroblasts, Krüppel-like factor 15 negatively regulated Ang II-induced IL-11 expression. Ang II increased extracellular signal-regulated kinases 1 and 2 activation, especially in adventitia, and caused biphasic extracellular signal-regulated kinases 1 and 2 activation in adventitial fibroblasts. A rapid and early activation increased IL-11 production through decreasing Krüppel-like factor 15 expression, which, in turn, induced the second extracellular signal-regulated kinases 1 and 2 activation, resulting in posttranscriptional profibrotic gene expression. Conclusions These results demonstrate that extracellular signal-regulated kinases 1 and 2 activation is important for Krüppel-like factor 15-mediated IL-11 expression in adventitial fibroblasts to promote adventitial remodeling in Ang II-induced hypertension. Therefore, targeting the Krüppel-like factor 15/IL-11 axis might serve as a new therapeutic strategy for vascular diseases.

In China, hepatocellular carcinoma (HCC) is considered a malignant tumor with poor prognosis, frequent metastasis, and a high relapse rate. Telocytes (TCs) participate in tumorigenic, invasive, and migratory processes by secreting functional proteins and transmitting cell-to-cell information, but their functions in HCC are still unknown. TC counts and MMP9 expression in liver cancer tissues were measured using immunohistochemistry, western blotting, and RT-PCR. Primary TCs from liver para-cancer tissues were cultured in vitro. To verify the role of TCs in HCC, a metastatic cancer animal model was established using three types of liver cancer cell lines in vivo. TCs promoted HCC cell metastasis by MMP9 expression in vitro and in vivo. Platelet-derived growth factor-alpha (PDGF-α), secreted by HCC cells, activated the Ras/ERK signaling pathway in TCs, thereby increasing MMP9 expression; Moreover, miR-942-3p suppressed MMP9 expression in TCs. Our results reveal the role of TCs in HCC and the mechanisms by which they elicit their effects, and they may serve as novel prognostic markers for HCC., (© 2021. The Author(s).)