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Although Chinese herbal medicine (CHM) has been widely used as an adjunctive therapy for colorectal cancer in Asia, its efficacy is not well defined. The purpose of this systematic review is to assess the efficacy of CHM as an adjunctive therapy to chemotherapy for the patients with colorectal cancer. Randomized controlled trials with CHM to treat colorectal cancer were extensively searched in seven databases. Two researchers independently assessed the quality and validity of included trials and extracted outcome data for synthesis. 20 trials were included for analysis. Compared to using chemotherapy alone, CHM combined with chemotherapy significantly increased 1- and 3-year survival rate [odds ratio (OR) 2.41, 95% confidence interval (CI) 1.32-4.41; OR 2.40, 95% CI 1.49-3.87]. The combined therapy significantly slowed colorectal cancer progression (OR 0.50, 95% CI 0.32-0.77) and improved quality of life (OR 3.43, 95% CI 2.35-5.02). It had positive effects in immunoregulation. CHM as an adjunctive therapy also had significant advantages in reducing the adverse effects of chemotherapy. This systematic review suggests that CHM as an adjunctive therapy with chemotherapy versus chemotherapy alone has significant efficacy in terms of prolonging survival, enhancement of tumor response, improvement of quality of life, immunoregulation, and alleviation of acute adverse effects. However, a firm conclusion could not be reached because of the poor quality of the included trials. Further trials with higher quality are required and the efficacy in other forms of advantages remains to be further determined. [ABSTRACT FROM AUTHOR]

The mechanism by which TGF-[beta] regulates renal inflammation and fibrosis is largely unclear; however, it is well accepted that its biological effects are mediated through Smad2 and Smad3 phosphorylation. Following activation, these Smads form heteromeric complex with Smad4 and translocate into the nucleus to bind and regulate the expression of target genes. Here we studied the roles of Smad4 to regulate TGF-[beta] signaling in a mouse model of unilateral ureteral obstruction using conditional Smad4 knockout mice and in isolated Smad4 mutant macrophages and fibroblasts. Disruption of Smad4 significantly enhanced renal inflammation as evidenced by a greater CD45(+) leukocyte and F4/80(+) macrophage infiltration and upregulation of IL-1[beta], TNF-[alpha], MCP-1, and ICAM-1 in the obstructed kidney and in IL-1[beta]-stimulated macrophages. In contrast, deletion of Smad4 inhibited renal fibrosis and TGF-[beta]1-induced collagen I expression by fibroblasts. Further studies showed that the loss of Smad4 repressed Smad7 transcription, leading to a loss of functional protein. This, in turn, inhibited I[kappa]B[alpha] expression but enhanced NF-[kappa]B activation, thereby promoting renal inflammation. Interestingly, deletion of Smad4 influenced Smad3-mediated promoter activities and the binding of Smad3 to the COL1A2 promoter, but not Smad3 phosphorylation and nuclear translocation, thereby inhibiting the fibrotic response. Thus, Smad4 may be a key regulator for the diverse roles of TGF-[beta]1 in inflammation and fibrogenesis by interacting with Smad7 and Smad3 to influence their transcriptional activities in renal inflammation and fibrosis. [ABSTRACT FROM AUTHOR]

The goal of this study was to investigate the possible therapy mechanism of triterpene acids of Eriobotrya japonica (Thunb.) Lindl. Leaf (TAL) in alveolar macrophage (AM) of chronic bronchitis (CB) rats. CB model was established by injection of bacillus calmette guein (BCG) plus lipopolisacharide (LPS) in rats. TAL significantly inhibited the increased NO concentration, iNOS expression and phosphorylation of p38 MAPK in alveolar macrophages (AMs) of CB rats. Using in vivo test, we found that SB203580, a p38 MAPK inhibitor, (10 muM) significantly inhibited inducible nitric oxide synthase (iNOS) mRNA expression in AM. This data indicate that TAL highly decreases excessive iNOS expression and NO induction, and p38 MAPK signal transduction participates in iNOS expression and NO induction in AM of CB rats. The effect of TAL on iNOS expression in AM may be related to its inhibition of p38 MAPK signal transduction. [ABSTRACT FROM AUTHOR]

Background: Antithyroid drugs (ATDs) are the preferred treatment option for Graves' disease (GD), yet there is a lack of systematic evaluations studying the relationship between treatment duration and therapeutic outcomes. This study aims to assess the remission rate (RR) in children with GD under ATDs therapy and to conduct an analysis of associated factors., Method: Systematically searched PubMed, Embase, Cochrane Library, Web of Science, China National Knowledge Infrastructure and Wanfang database, with a search time limit from the establishment of the database to 23 November 2023. The primary outcome was the RR. The pooled RR was calculated and subgroup comparisons were performed. Meta-analysis was conducted using R Studio 2023.09.0 + 463 software., Results: The study incorporated a total of 19 research projects, which collectively involved 3359 paediatric patients diagnosed with GD (comprising 2600 girls and 759 boys). The overall RR for paediatric GD treated with ATDs was 25.4% (95% Confidence Interval [CI]: 20.7%, 30.1%). The pooled RR following treatment durations of < 2 years, 2-5 years, and > 5 years were respectively 15.5%, 24.1% and 33.0%. Meta-regression results indicated that the duration of treatment and follow-up duration were significant sources of high heterogeneity among the studies. Specifically, for every additional year of ATDs treatment, there was an increase in the RR by 3.8% (Coefficient = 3.8%, 95% CI: 0.6%, 7.0%, p < 0.01)., Conclusion: The overall RR for the treatment of paediatric GD with ATDs is 25.4%, and prolonging the treatment course can indeed lead to an increased RR., (© 2024 The Author(s). Clinical Endocrinology published by John Wiley & Sons Ltd.)

A facile method for the synthesis of aminodiborane (NH 2 B 2 H 5 , ADB) has been developed through the reaction of ammonia borane (NH 3 BH 3 , AB) with an ether solution of hydrogen chloride (HCl·Et 2 O) at room temperature. In addition, N -alkyl substituted ADB derivatives were synthesized by reacting N -alkyl substituted AB with HCl·Et 2 O at 50 °C. The mechanistic studies indicated that the nucleophilic substitution reaction of the B-H bonding pair electrons and the dihydrogen bonding interaction play an important role. This work paves an alternative way to prepare amine borane compounds.

Hypothyroidism is a known adverse event associated with the use of immune checkpoint inhibitors (ICIs) in cancer treatment. This study aimed to develop an interpretable machine learning (ML) model for individualized prediction of hypothyroidism in patients treated with ICIs. The retrospective cohort of patients treated with ICIs was from the First Affiliated Hospital of Ningbo University. ML methods applied include logistic regression (LR), random forest classifier (RFC), support vector machine (SVM), and extreme gradient boosting (XGBoost). The area under the receiver-operating characteristic curve (AUC) was the main evaluation metric used. Furthermore, the Shapley additive explanation (SHAP) was utilized to interpret the outcomes of the prediction model. A total of 458 patients were included in the study, with 59 patients (12.88%) observed to have developed hypothyroidism. Among the models utilized, XGBoost exhibited the highest predictive capability (AUC = 0.833). The Delong test and calibration curve indicated that XGBoost significantly outperformed the other models in prediction. The SHAP method revealed that thyroid-stimulating hormone (TSH) was the most influential predictor variable. The developed interpretable ML model holds potential for predicting the likelihood of hypothyroidism following ICI treatment in patients. ML technology offers new possibilities for predicting ICI-induced hypothyroidism, potentially providing more precise support for personalized treatment and risk management., (© 2024 The Author(s). Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Aim: The study objective was to evaluate the primary feasibility of endoscopic submucosal resection (ESD) and endoscopic full-thickness resection (EFTR) via balloon-assisted enteroscopy (BAE) to treat small bowel subepithelial lesions (SELs)., Method: A retrospective case series study was performed. The first fifteen consecutive patients who underwent ESD (n = 10) and EFTR (n = 5) via BAE to remove small bowel SELs from November 2016 to December 2023 were included. The main outcome measures were the technique success rate, operative time and complication rate., Results: This research focused on 15 cases of jejunoileal SELs, four cases of lipomyoma, three cases of ectopic pancreas, two cases of NETs, three cases of benign fibrous tumours and three cases of angioma. The overall technique success rate was 86.7%, with 100% (10/10) and 60% (3/5) for BAE-ESD and BAE-EFTR, respectively, in removing small bowel SELs. Two cases of EFTR failed, as the BAE operation was unsuitable for tumour resection and suture repair of a perforated wound. No serious bleeding or any postoperative complications occurred. The median time of endoscopic resection via BAE for SELs was 44 min (range 22-68 min)., Conclusion: ESD and EFTR via BAE might be alternative choices for treating small SELs in the small bowel, with the advantages of clear and accurate positioning and minimal invasiveness. However, its superiority over surgery still needs to be further investigated., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Tangshenning (TSN) is a safe and effective formula to treat diabetic nephropathy (DN), and clinical studies have demonstrated that its therapeutic effects are related to oxidative stress improvements in patients. Herein, this study aims to explore the potential mechanism of how TSN alleviates diabetic renal tubular injury., Methods: The ultrahigh pressure liquid chromatography-quadrupole-time of flight mass spectrometry (UPLC-QTOF/MS) was used to identify the chemical composition and serum components of TSN. KK-Ay mice served to investigate the protective effects and regulatory mechanisms of TSN on tubular damage in DN. Furthermore, inhibitors and inducers of ferroptosis were employed in high glucose-cultured tubular epithelial cells (TECs) to verify the potential mechanisms of TSN. The expressions of proteins related to renal tubular injury, ferroptosis and solute carrier family 7, member 11 (SLC7A11)/glutathione (GSH)/glutathione peroxidase 4 (GPX4) axis were analyzed by western blot and immunofluorescence. Mitochondrial ultrastructure was observed in kidney tissues and TECs by a transmission electron microscope. Pathological changes in the renal tissues were observed by HE, PAS, and Prussian blue staining. Ferroptosis-related reactive oxygen species (ROS), malondialdehyde (MDA), ferrous ion, the intake of cystine, GSH, and oxidized glutathione (GSSG) were evaluated and contrasted in vivo or in vitro., Results: 51 compounds of TSN powder and 11 components in TSN-containing serum were identified by UPLC-QTOF/MS method. Administration of TSN ameliorated the elevated levels of proteinuria, serum creatinine, blood urea nitrogen, abnormal expression of renal tubular injury markers, and pathological damage to the renal tubules in DN mice model. Intriguingly, a strong inhibition of ferroptosis after TSN treatment occurred in both DN mice model and high glucose-cultured TECs. Notably, induction of ferroptosis by erastin attenuated the protective effect of TSN in high glucose-cultured TECs, while the ferroptosis inhibition by ferrostatin-1 treatment protected renal tubular, which was similar to TSN, suggesting the contribution of TSN-mediated by the inhibition of ferroptosis in DN progression. Mechanistically, TSN upregulated the SLC7A11/GSH/GPX4 axis to inhibit ferroptosis., Conclusion: TSN may delay the DN progression and attenuate the renal tubular injury by inhibiting the ferroptosis regulated by the SLC7A11/GSH/GPX4 axis., (© 2024. The Author(s).)

Cognitive impairments, which can be caused by neurodegenerative and cerebrovascular disease, represent a growing global health crisis with far-reaching implications for individuals, families, healthcare systems, and economies worldwide. Notably, neurodegenerative-induced cognitive impairment often presents a different pattern and severity compared to cerebrovascular-induced cognitive impairment. With the development of computational technology, machine learning techniques have developed rapidly, which offers a powerful tool in radiomic analysis, allowing a more comprehensive model that can handle high-dimensional, multivariate data compared to the traditional approach. Such models allow the prediction of the disease development, as well as accurately classify disease from overlapping symptoms, therefore facilitating clinical decision making. This review will focus on the application of machine learning-based radiomics on cognitive impairment caused by neurogenerative and cerebrovascular disease. Within the neurodegenerative category, this review primarily focuses on Alzheimer's disease, while also covering other conditions such as Parkinson's disease, Lewy body dementia, and Huntington's disease. In the cerebrovascular category, we concentrate on poststroke cognitive impairment, including ischemic and hemorrhagic stroke, with additional attention given to small vessel disease and moyamoya disease. We also review the specific challenges and limitations when applying machine learning radiomics, and provide our suggestion to overcome those limitations towards the end, and discuss what could be done for future clinical use., Competing Interests: The authors declare they have no conflict of interest., (© 2024 The Author(s). MedComm published by Sichuan International Medical Exchange & Promotion Association (SCIMEA) and John Wiley & Sons Australia, Ltd.)

Background Early-life exposure to famine may influence the occurrence of chronic diseases and aging in midlife among those exposed. This study aims to explore the relationship between exposure to the Chinese Great Famine and aging in middle-aged individuals. Methods Participants born in 1963-1965 (unexposed), 1959-1961 (in utero exposure), and 1955-1957 (childhood exposure) from the Kailuan Study were included. Their biological age at 2010, 2014, and 2018 was investigated, and age acceleration (biological age minus actual age) was calculated to assess aging. Logistic regression analysis was employed to describe the relationship between famine exposure and the aging risk. Subgroup and sensitivity analysis were conducted to explore differences and stability in this relationship among different groups. Results A total of 17,543 participants were included in this study. Among them, 12,762 (72.7%) were male, and 4,781 (27.3%) were female, with 2,543 participants experiencing aging events. Compared to unexposed participants, those exposed during childhood and in utero exhibited a 1.69-fold (OR = 1.69, 95%CI: 1.53-1.87) and 1.22-fold (OR = 1.22, 95%CI: 1.08-1.37) increased risk of aging. Subgroup analysis revealed an interaction with income (P for interaction = 0.008), and additional interaction analysis suggested that increasing income could partially mitigate the detrimental effects of early-life famine exposure. Furthermore, experiencing famine in severely affected regions exacerbated the risk of aging (OR = 1.41, 95%CI: 1.21-1.63). Conclusion Exposure to famine in utero or during childhood may elevate the risk of midlife aging among exposed individuals, and these relationships are influenced by the severity of famine exposure. Increasing income may also help mitigate these effects.Trial registration: Kailuan study, ChiCTRTNRC11001489. Registered July 19, 2015 Retrospectively registered, https//www.chictr.org.cn/showprojEN.html?proj=8050&u&#95;atoken=af46a0dee8d73f320bb5459ab7bbcfa9&u&#95;asig=1a0c381017255295896468605e00cf ., (© 2024. The Author(s).)

Porcine reproductive and respiratory syndrome caused by porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically devastating viral diseases in the global pork industry. To further clarify the epidemic characteristics of the virus, 365 clinical samples were collected from diseased pigs suffering from abortion and respiratory disease from 2018 to 2023 on 63 pig farms in Henan and Shanxi provinces, and screened for the presence of PRRSV using reverse transcription-polymerase chain reaction (RT-PCR). A total of 62 clinical samples (62/365, 16.99 %) were positive for PRRSV, and subsequently, full-length ORF5 gene sequences of 29 PRRSV strains and the complete genome sequence of one PRRSV HeN-HC isolate were obtained and analyzed. Phylogenetic analysis based on the ORF5 gene showed that 22 of the 29 PRRSV2 strains belonged to sublineage 1.8 (NADC30-like), 5 belonged to sublineage 8.5 (HP-PRRSV), and 2 belonged to sublineage 5.1 (VR-2332-like), indicating that both HP-PRRSV and NADC30-like strains were mainly circulating in Henan and Shanxi provinces. Compared to VR-2332 strain, different types of amino acid mutations were found in the GP5 protein of these 29 strains, and the amino acid deletions were displayed in the Nsp2 protein of the HeN-HC isolate, leading to the variation of protein structures. It is noteworthy that recombination events were identified in the HeN-Ping and HeN-B strains. In addition, a total of 60, 094 pig serum samples from Henan province were collected, and the positive rate of specific antibodies against PRRSV was 86.37 % from 2019 to 2022, and 86.66 %, 84.85 %, 87.54 % and 86.30 % in 2019, 2020, 2021 and 2022, respectively. Overall, this study provides valuable insights into the molecular epidemiology and evolution of PRRSV circulating in central China., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

In recent decades, nanotechnology has significantly advanced drug delivery systems, particularly in targeting subcellular organelles, thus opening new avenues for disease treatment. Mitochondria, critical for cellular energy and health, when dysfunctional, contribute to cancer, neurodegenerative diseases, and metabolic disorders. This has propelled the development of nanomedicines aimed at precise mitochondrial targeting to modulate their function, marking a research hotspot. This review delves into the recent advancements in mitochondrial-targeted nanotherapeutics, with a comprehensive focus on targeting strategies, nanocarrier designs, and their therapeutic applications. It emphasizes nanotechnology's role in enhancing drug delivery by overcoming biological barriers and optimizing drug design for specific mitochondrial targeting. Strategies exploiting mitochondrial membrane potential differences and specific targeting ligands improve the delivery and mitochondrial accumulation of nanomedicines. The use of diverse nanocarriers, including liposomes, polymer nanoparticles, and inorganic nanoparticles, tailored for effective mitochondrial targeting, shows promise in anti-tumor and neurodegenerative treatments. The review addresses the challenges and future directions in mitochondrial targeting nanotherapy, highlighting the need for precision, reduced toxicity, and clinical validation. Mitochondrial targeting nanotherapy stands at the forefront of therapeutic strategies, offering innovative treatment perspectives. Ongoing innovation and research are crucial for developing more precise and effective treatment modalities., 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 Li, Li, Wei and Ye.)

Microsporidium Ecytonucleospora hepatopenaei (EHP) spores were purified from the hepatopancreas of Penaeus vannamei infected with EHP by percoll density gradient centrifugation and differential centrifugation. The EHP spores contain a thick chitin wall and might not rupture using the routine DNA extraction protocol. In this study, three enzymes were used, including chitinase, proteinase K, and DNase I. Chitinase or proteinase K digestions caused weakened fluorescence of chitin showing by a blurred edge of EHP spores stained with calcofluor white under a fluorescence microscope. Different combinations of these enzymes followed by DNA extraction with phenol-chloroform from EHP spores showed significant increases in the copy number of the EHP SSU gene per spore. The combination of the chitinase and proteinase K treatments resulted 4.46 ± 1.07 copies/spore detected, which is 31.6 ± 20.7 folds of no treatment groups, accounting to (55.7 ± 13.4)% of the total copies of the gene in the spore. The additional treatment with chitinase to the conventional extraction protocol with a proteinase K digestion step for feces and hepatopancreas samples of P. vannamei resulted in a significant difference in EHP copies in the DNA of (83.8 ± 64.1)% and (55.3 ± 88.0)% increases. The study proved that chitinase and proteinase K treatment enhance the DNA extraction from microsporidian spores resulting in high yield., 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. Published by Elsevier Inc.)

Key Message: Abnormal expression of genes regulating anther and pollen development and insufficient accumulation of male sterility (MS)- related metabolites lead to MS in cybrid pummelo Male sterility (MS) is a major cause of seedlessness in citrus, which is an important trait for fresh fruit. Understanding the mechanism of MS is important for breeding seedless citrus cultivars. In this study, we dissected the transcriptional, metabolic and physiological mechanisms of MS in somatic cybrid of pummelo (G1 + HBP). G1 + HBP exhibited severe male sterility, manifesting as retarded anther differentiation, abnormal anther wall development (especially tapetum and endothecium), and deficient pollen wall formation. In the anthers of G1 + HBP, the expression of genes regulating anther differentiation and tapetum development was abnormal, and the expression of genes regulating endothecium secondary lignification thickening and pollen wall formation was down-regulated. The transcription of genes involved in MS-related biological processes, such as jasmonic acid (JA) signaling pathway, primary metabolism, flavonoid metabolism, and programmed cell death, was altered in G1 + HBP anthers, and the accumulation of MS-associated metabolites, including fatty acids, amino acids, sugars, ATP, flavonols and reactive oxygen species (ROS), was down-regulated in G1 + HBP anthers. In summary, abnormal expression of key genes regulating anther and pollen development, altered transcription of key genes involved in MS-related metabolic pathways, and insufficient accumulation of MS-related metabolites together lead to MS in G1 + HBP. The critical genes and the metabolism pathways identified herein provide new insights into the formation mechanism of MS in citrus and candidate genes for breeding seedless citrus., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: High densities of tumor infiltrating CD3 and CD8 T-cells are associated with superior prognosis in colorectal cancer (CRC). Their value as predictors of benefit from adjuvant chemotherapy is uncertain., Patients and Methods: Tumor tissue from 868 patients in the QUASAR trial (adjuvant fluorouracil/folinic acid v observation in stage II/III CRC) was analyzed by CD3 and CD8 immunohistochemistry. Pathologists, assisted by artificial intelligence, calculated CD3 and CD8 cell densities (cells/mm 2 ) in the core tumor (CT) and invasive margin (IM). Participants were randomly partitioned into training and validation sets. The primary outcome was recurrence-free interval (RFI), 2-year RFI for assessment of biomarker-treatment interactions. Maximum-likelihood methods identified optimal high-risk/low-risk group cutpoints in the training set. Prognostic analyses were repeated in the validation set., Results: In the training set, the recurrence rate in the high-risk group was twice that in the low-risk group for all measures (CD3-CT: rate ratio [RR], 2.00, P = .0008; CD3-IM: 2.38, P < .00001; CD8-CT: 2.17, P = .0001; CD8-IM: 2.13, P = .0001). This was closely replicated in the validation set (RR, 1.96, 1.79, 1.72, 1.72, respectively). In multivariate analyses, prognostic effects were similar in colon and rectal cancers, and in stage II and III disease. Proportional reductions in recurrence with adjuvant chemotherapy were of similar magnitude in the high- and low-recurrence risk groups. Combining information from CD3-IM and CD3-CT (CD3 Score) generated high-, intermediate-, and low-risk groups with numbers needed to treat (NNTs) to prevent one disease recurrence being 11, 21, and 36, respectively., Conclusion: Recurrence rates in the high-risk CD3/CD8 groups are twice those in the low-risk groups. Proportional reductions with chemotherapy are similar, allowing NNTs derived in QUASAR to be updated using contemporary, nonrandomized data sets.

The Huaihe River Basin is located in the north-south climate transition zone of China. The change of carbon storage in this area is of great significance for predicting the future ecological protection, mitigating climate change, and maintaining sustainable development of the Huaihe River Basin. The middle and upper reaches of Huaihe River Basin （above Bengbu station） were taken as the research area. Based on the land use data from 1980 to 2020, the PLUS model was used to simulate and predict the land use types in the study area from 2030 to 2100 under the scenarios of SSP1-2.6, SSP2-4.5, SSP5-8.5, and the continuation of land use status. The carbon module in the InVEST model was used to simulate and predict the carbon storage from 1980 to 2020 and the carbon storage from 2030 to 2100 under various scenarios, and the spatial and temporal changes of carbon storage in the middle and upper reaches of the Huaihe River Basin were compared and analyzed. The results showed that： ① From 1980 to 2020, the basin showed a decrease in both cultivated land and grassland,and the area of forest,water, construction, and unused land all increased, among which the area of cultivated land continued to decrease, with a total decrease of 4 699 km 2 in 40 a. Construction land continued to increase, with a total increase of 4 592 km 2 in 40 a. ② The carbon storage in the basin showed a downward trend, with a total reduction of 1.05×10 7 t from 1980 to 2020. ③ In the four scenarios, the area of each land type had different degrees of change, and that of the SSP1-2.6 scenario was relatively small out of the four scenarios. ④ Compared with the carbon storage in 2020, the carbon storage in the SSP1-2.6 scenario increased by 8.7×10 4 t, the carbon storage in the SSP2-4.5 scenario decreased by 1.42×10 7 t, the carbon storage in the SSP5-8.5 scenario decreased by 1.34×10 7 t, and the carbon storage in the current continuation scenario decreased by 1.22×10 7 t. The study can provide a scientific basis for land use structure management and ecological protection in the middle and upper reaches of the Huaihe River Basin （above Bengbu station） in the future.

Porcine epidemic diarrhea virus (PEDV) infection causes severe diarrhea and high mortality in neonatal piglets. Pseudorabies causes acute and often fatal infections in young piglets, respiratory disorders in growing pigs, and reproductive failure in sows. In late 2011, pseudorabies virus (PRV) variants occurred in Bartha-K61-vaccine-immunized swine herds, resulting in economic losses to the global pig industry. Therefore, it is essential to develop a safe and effective vaccine against both PEDV and PRV infections. In this study, we constructed a recombinant virus rPRV-PEDV S1 expressing the major neutralizing epitope region (COE, SS2, and SS6) of the PEDV S1 protein by homologous recombination technology and CRISPR/Cas9 gene editing technology, and then evaluated its biological characteristics in vitro and immunogenicity in pigs. The recombinant virus rPRV-PEDV S1 had similar growth kinetics in vitro to the parental rPRV NY-gE - /gI - /TK - strain, and was proven genetically stable in swine testicle (ST) cells and safe for piglets. PEDV S1-specific antibodies were detected in piglets immunized with rPRV-PEDV S1 on the 7th day post-immunization (dpi), and the antibody level increased rapidly at 14-21 dpi. Moreover, the immunized piglets receiving the recombinant virus exhibited alleviated clinical signs and reduced viral load compared to the unvaccinated group following a virulent PEDV HN2021 strain challenge. Also, piglets immunized with rPRV-PEDV S1 developed a PRV-specific humoral immune response and elicited complete protection against a lethal PRV NY challenge. These data indicate that the recombinant rPRV-PEDV S1 is a promising vaccine candidate strain for the prevention and control of PEDV and PRV infections.

Under the background of "dual carbon", the impact of the implementation of the Grain for Green project on the carbon storage of the ecosystem in the Yellow River Basin must be explored, which can serve as an important reference for improving the policy implementation of the new round of the Grain for Green project and improving the carbon sink capacity of the ecosystem in the Yellow River Basin. In this study, 1990, before the implementation of the project, was selected as the starting year of the research period, and 2020, after the implementation of the two rounds of the project, was selected as the end year of the research period. Based on the ecosystem type data from 1990 to 2020, the InVEST model was used to calculate the soil carbon pool, underground carbon pool, below carbon pool, dead organic matter carbon pool, and total carbon storage of ecosystems in the Yellow River Basin and the area where the project was implemented from 1990 to 2020. The results showed that： ① From 1990 to 2020, the area of forest ecosystem in the Yellow River Basin expanded by 26 610.06 km 2 , and the area of farmland decreased by 46 849.06 km 2 after the implementation of two rounds of the project. Spatially, the upper reaches of the Yellow River were dominated by grassland and other ecosystems； the middle reaches of the Yellow River were dominated by farmland, forest, and grassland ecosystems； and the lower reaches of the Yellow River were dominated by farmland ecosystems. ② From 1990 to 2020, the carbon storage in the project implementation area showed a fluctuating and increasing trend, and the total carbon storage reached a peak （219.47×10 8 t） in 2009 and decreased to 218.59×10 8 t in 2020 due to the decrease of grassland ecosystem from 2010 to 2020. Spatially, the high-value areas of carbon storage were distributed in Aba Tibetan and Qiang Autonomous Prefecture of Sichuan Province and the southern tip of Gansu Province in the upper reaches of the forest and grass accumulation and in the whole of Shanxi Province and the central and southern parts of Shaanxi Province in the middle reaches. Shangluo City in Shaanxi Province and Alxa League in Inner Mongolia Autonomous Region were prefecture-level cities with the highest and lowest average carbon density. ③ In 2035, the carbon storage loss of the natural development scenario was predicted to be 0.83×10 8 t, and the other three scenarios would increase this loss. Under the moderate farmland return scenario, the Yellow River Basin ecosystem had the strongest carbon sequestration capacity, and the predicted carbon storage would increase by 2.72×10 8 t compared with that in 2020, and the deep farmland return scenario was the comprehensive optimal scenario. Therefore, in the future, the Yellow River Basin could refer to the deep farmland return scenario to optimize and adjust the implementation plan of the Grain for Green project, and the predicted value of carbon storage can provide some data support for achieving the dual carbon goal.

The appearance of disordered lithium dendrites and fragile solid electrolyte interfaces (SEI) significantly hinder the serviceability of lithium metal batteries. Herein, guided by theoretical predictions, a multi-component covalent triazine framework with partially electronegative channels (4C-TA 0.5 TF 0.5 -CTF) is incorporated as a protective layer to modulate the interface stability of the lithium metal batteries. Notably, the 4C-TA 0.5 TF 0.5 -CTF with optimized electronic structure at the molecular level by fine-tuning the local acceptor-donor functionalities not only enhances the intermolecular interaction thereby providing larger dipole moment and improved crystallinity and mechanical stress, but also facilitates the beneficial effect of lithiophilic sites (C-F bonds, triazine cores, C=N linkages and aromatic rings) to further regulate the migration of Li + and achieve a uniform lithium deposition behavior as determined by various in-depth in/ex situ characterizations. Due to the synergistic effect of multi-component organic functionalities, the 4C-TA 0.5 TF 0.5 -CTF modified full cells perform significantly better than the common two/three-component 2C-TA-CTF and 3C-TF-CTF electrodes, delivering an excellent capacity of 116.3 mAh g -1 (capacity retention ratio: 86.8 %) after 1000 cycles at 5 C and improved rate capability. This work lays a platform for the prospective molecular design of improved organic framework relative artificial SEI for highly stable lithium metal batteries., (© 2024 Wiley-VCH GmbH.)

We report here on the structure-activity relationships of hybrids combining 3-descladinosyl clarithromycin with quinolones linked by extended diamine connectors. Several hybrids, exemplified by 23Bc, 23Be, 23Bf, 26Be, and 30Bc, not only restored potency against inducibly resistant pathogens but also exhibited significantly enhanced activities against constitutively resistant strains of Staphylococcus pneumoniae and Staphylococcus pyogenes, which express high-level resistance independent of clarithromycin or erythromycin induction. Additionally, the novel hybrids showed susceptibility against Gram-negative Haemophilus influenzae. Notably, hybrid 23Be demonstrated dual modes of action by inhibiting both protein synthesis and DNA replication in vitro and in vivo. Given these promising characteristics, 23Be emerges as a potential candidate for the treatment of community-acquired bacterial pneumonia., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Jian-Hua Liang reports financial support was provided by National Key Research and Development Program of China. Nothing to declare. If there are other authors, they 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 Masson SAS. All rights reserved.)

Gut microbiota dysbiosis has been implicated in rheumatoid arthritis (RA) and influences disease progression. Although molecular and culture-independent studies revealed RA patients harbored a core microbiome and had characteristic bacterial species, the lack of cultured bacterial strains had limited investigations on their functions. This study aimed to establish an RA-originated gut microbial biobank (RAGMB) that covers and further to correlates and validates core microbial species on clinically used and diagnostic inflammation and immune indices. We obtained 3200 bacterial isolates from fecal samples of 20 RA patients with seven improved and 11 traditional bacterial cultivation methods. These isolates were phylogenetically identified and selected for RAGMB. The RAGMB harbored 601 bacterial strains that represented 280 species (including 43 novel species) of seven bacterial phyla. The RAGMB covered 93.2% at species level of medium- and high-abundant (relative abundances ≥0.2%) RA gut microbes, and included four rare species of the phylum Synergistota . The RA core gut microbiome was defined and composed of 20 bacterial species. Among these, Mediterraneibacter tenuis and Eubacterium rectale were two species that statistically and significantly correlated with clinically used diagnostic indices such as erythrocyte sedimentation rate (ESR) and IL-10. Thus, M. tenuis and E. rectale were selected for experimental validation using DSS-treated and not DSS-treated mice model. Results demonstrated both M. tenuis and E. rectale exacerbated host inflammatory responses, including shortened colon length and increased spleen weight, decreased IL-10 and increased IL-17A levels in plasma. Overall, we established the RAGMB, defined the RA core microbiome, correlated and demonstrated core microbial species effected on host inflammatory and immune responses. This work provides diverse gut microbial resources for future studies on RA etiology and potential new targets for new biomedical practices., Competing Interests: The authors declare no conflict of interest., (© 2024 The Author(s). iMeta published by John Wiley & Sons Australia, Ltd on behalf of iMeta Science.)

Behavioral despair is one of the clinical manifestations of major depressive disorder and an important cause of disability and death. However, the neural circuit mechanisms underlying behavioral despair are poorly understood. In a well-established chronic behavioral despair (CBD) mouse model, using a combination of viral tracing, in vivo fiber photometry, chemogenetic and optogenetic manipulations, in vitro electrophysiology, pharmacological profiling techniques, and behavioral tests, we investigated the neural circuit mechanisms in regulating behavioral despair. Here, we found that CBD enhanced CaMKIIα neuronal excitability in the dorsal dentate gyrus (dDG) and dDGCaMKIIα neurons involved in regulating behavioral despair in CBD mice. Besides, dDGCaMKIIα neurons received 5-HT inputs from median raphe nucleus (MRN) and were mediated by 5-HT1A receptors, whereas MRN5-HT neurons received CaMKIIα inputs from lateral hypothalamic (LH) and were mediated by AMPA receptors to regulate behavioral despair. Furthermore, fluvoxamine exerted its role in resisting behavioral despair through the LH-MRN-dDG circuit. These findings suggest that a previously unidentified circuit of LHCaMKIIα-MRN5-HT-dDGCaMKIIα mediates behavioral despair induced by CBD. Furthermore, these support the important role of AMPA receptors in MRN and 5-HT1A receptors in dDG that might be the potential targets for treatment of behavioral despair, and explain the neural circuit mechanism of fluvoxamine-resistant behavioral despair., (© The Author(s) 2024. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: The obesity paradox has been reported among older adults. However, whether the favorable effect of obesity is dependent on metabolic status remains largely unknown. We aimed to explore the association of metabolic obesity phenotypes and their changes with all-cause mortality among the Chinese oldest-old population., Methods: This prospective cohort study included 1207 Chinese oldest old (mean age: 91.8 years). Metabolic obesity phenotypes were determined by central obesity and metabolic status, and participants were classified into metabolically healthy obesity (MHO), metabolically unhealthy obesity (MUO), metabolically healthy non-obesity (MHN), and metabolically unhealthy non-obesity (MUN). The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox regression models., Results: During 5.3 years of follow-up, 640 deaths were documented. Compared with non-obesity, obesity was associated with a decreased mortality risk among participants with metabolically healthy (HR, 0.75; 95% CI, 0.63-0.91) while this association was insignificant among metabolically unhealthy. Compared to MHO, MHN (HR, 1.27; 95% CI, 1.06-1.53) and MUN (HR, 1.49; 95% CI, 1.10-2.02) were significantly associated with an increased mortality risk. Compared to those with stable MHO, those transited from MHO to MUO demonstrated a higher mortality risk (HR, 1.81; 95% CI, 1.06-3.11)., Conclusions: MHO predicts better survival among the Chinese oldest-old population. These findings suggest that ensuring optimal management of metabolic health is beneficial and taking caution in weight loss based on the individual body weight for the metabolically healthy oldest-old adults., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Alzheimer's disease (AD) represents the most widespread neurodegenerative disorder, distinguished by a gradual onset and slow progression, presenting a substantial challenge to global public health. The mitochondrial-associated membrane (MAMs) functions as a crucial center for signal transduction and material transport between mitochondria and the endoplasmic reticulum, playing a pivotal role in various pathological mechanisms of AD. The dysregulation of mitochondrial quality control systems is considered a fundamental factor in the development of AD, leading to mitochondrial dysfunction and subsequent neurodegenerative events. Recent studies have emphasized the role of MAMs in regulating mitochondrial quality control. This review will delve into the molecular mechanisms underlying the imbalance in mitochondrial quality control in AD and provide a comprehensive overview of the role of MAMs in regulating mitochondrial quality control., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Acute kidney injury (AKI) manifests as a clinical syndrome characterised by the rapid accumulation of metabolic wastes, such as blood creatinine and urea nitrogen, leading to a sudden decline in renal function. Currently, there is a lack of specific therapeutic drugs for AKI. Previously, we identified gastrin-releasing peptide receptor (GRPR) as a pathogenic factor in AKI. In this study, we investigated the therapeutic potential of a novel Chinese medicine monomer, aurantiamide (AA), which exhibits structural similarities to our previously reported GRPR antagonist, RH-1402. We compared the therapeutic efficacy of AA with RH-1402 both in vitro and in vivo using various AKI models. Our results demonstrated that, in vitro, AA attenuated injury, necroptosis, and inflammatory responses in human renal tubular epithelial cells subjected to repeated hypoxia/reoxygenation and lipopolysaccharide stimulation. In vivo, AA ameliorated renal tubular injury and inflammation in mouse models of ischemia/reperfusion and cecum ligation puncture-induced AKI, surpassing the efficacy of RH-1402. Furthermore, molecular docking and cellular thermal shift assay confirmed GRPR as a direct target of AA, which was further validated in primary cells. Notably, in GRPR-silenced HK-2 cells and GRPR systemic knockout mice, AA failed to mitigate renal inflammation and injury, underscoring the importance of GRPR in AA's mechanism of action. In conclusion, our study has demonstrated that AA serve as a novel antagonist of GRPR and a promising clinical candidate for AKI treatment., 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 B.V. All rights reserved.)

DIV1 has the characteristics of fast transmission and a broad host range. Its infection leads to a high mortality rate, posing a serious threat to the global crustacean aquaculture industry. In order to increase the accuracy of DIV1 detection and reduce the difficulty of result interpretation, this study modified the original nested PCR method targeting the DIV1 ATPase gene. The internal primers for the nested PCR were redesigned to produce a 338 bp amplification product in the second step PCR, effectively distinguishing the target band from primer dimers. The newly established nested PCR method exhibits strong specificity and high sensitivity, with a detection limit as low as 1.37 × 10 1 copies/reaction. The developed nested PCR assay provides new technical support for the accurate detection of DIV1 in global crustacean aquaculture., 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.)

The reverse water gas shift reaction can be considered as a promising route to mitigate global warming by converting CO 2 into syngas in a large scale, while it is still challenging for non-Cu-based catalysts to break the trade-off between activity and selectivity. Here, the relatively high loading of Ni species is highly dispersed on hydroxylated TiO 2 through the strong Ni and -OH interactions, thereby inducing the formation of rich and stable Ni clusters (~1 nm) on anatase TiO 2 during the reverse water gas shift reaction. This Ni cluster/TiO 2 catalyst shows a simultaneous high CO 2 conversion and high CO selectivity. Comprehensive characterizations and theoretical calculations demonstrate Ni cluster/TiO 2 interfacial sites with strong CO 2 activation capacity and weak CO adsorption are responsible for its unique catalytic performances. This work disentangles the activity-selectivity trade-off of the reverse water gas shift reaction, and emphasizes the importance of metal-OH interactions on surface., (© 2024. The Author(s).)

Ligand engineering of aromatic heterocyclic cations in two-dimensional (2D) Dion-Jacobson (DJ) perovskites has been widely explored in recent years. In this study, how the positional isomers of aromatic heterocyclic cations tune the lattice of 2D perovskites, thereby influencing the transport and recombination dynamics of charge carriers, has been investigated through nonadiabatic molecular dynamics simulations. We demonstrate that the meta -substituted 3-(aminomethyl)pyridinium (3AMPY) cations greatly reduce the strength of electron-vibration coupling since the strong hydrogen-bonding network introduced by the changes in the arrangement of spacer cations significantly suppresses the structural thermal fluctuations. Compared to the para -substituted 4-(aminomethyl)pyridinium (4AMPY) cation, using the asymmetric 3AMPY as a spacer cation can achieve improved in-plane transport performance, enhanced thermal stability, and suppressed charge carrier recombination through weakening electron-vibration interactions. Our results explain the observed lifetime difference between the two types of DJ-phase perovskites in experiments and provide new guidance for optimizing the performance of perovskite devices.

Respiratory syncytial virus (RSV) is a significant cause of acute lower respiratory tract infections, particularly in vulnerable populations such as neonates, infants, young children, and the elderly. Among infants, RSV is the primary cause of bronchiolitis and pneumonia, contributing to a notable proportion of child mortality under the age of 5. In this study, we focused on investigating the pathogenicity of a lethal RSV strain, GZ08-18, as a model for understanding mechanisms of hypervirulent RSV. Our findings indicate that the heightened pathogenicity of GZ08-18 stems from compromised activation of intrinsic apoptosis, as evidenced by aberration of mitochondrial membrane depolarization in host cells. We thus hypothesized that enhancing intrinsic apoptosis could potentially attenuate the virulence of RSV strains and explored the effects of Rotenone, a natural compound known to stimulate the intrinsic apoptosis pathway, on inhibiting RSV infection. Our results demonstrate that Rotenone treatment significantly improved mouse survival rates and mitigated lung pathology following GZ08-18 infection. These findings suggest that modulating the suppressed apoptosis induced by RSV infection represents a promising avenue for antiviral intervention strategies., Competing Interests: Declaration of competing interest All authors of this submission declare that they have no competing interests related to the content of this manuscript. To the best of our knowledge, none of the authors have any financial, personal, or professional conflicts of interest that might have influenced the research presented in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Chronic kidney disease (CKD) is a clinical syndrome characterized by persistent renal function decline. Renal fibrosis is the main pathological process in CKD, but an effective treatment does not exist. Stratifin (SFN) is a highly-conserved, multi-function soluble acidic protein. Therefore, this study explored the effects of SFN on renal fibrosis. First, we found that SFN was highly expressed in patients with CKD, as well as in renal fibrosis animal and cell models. Next, transforming growth factor-beta 1 (TGF-β 1 ) induced injury and fibrosis in human renal tubule epithelial cells, and SFN knockdown reversed these effects. Furthermore, SFN knockdown mitigated unilateral ureteral obstruction (UUO)-induced renal tubular dilatation and renal interstitial fibrosis in mice. Liquid chromatography-tandem mass spectrometry/mass spectrometry (LC-MS/MS), co-immunoprecipitation (Co-IP), and immunofluorescence co-localization assays demonstrated that SFN bound the non-muscle myosin-encoding gene, myosin heavy chain 9 (MYH9), in the cytoplasm of renal tubular epithelial cells. MYH9 knockdown also reduced Col-1 and α-SMA expression, which are fibrosis markers. Finally, silencing SFN decreased MYH9 expression, alleviating renal fibrosis. These results suggest that SFN promotes renal fibrosis in CKD by interacting with MYH9. This study may provide potential strategies for the treatment of CKD., Competing Interests: Declaration of competing interest We declare that we do not have any commercial or associative interest that represents., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Histidine kinases (HKs) are important sensor proteins in fungi and play an essential role in environmental adaptation. However, the mechanisms by which fungi sense and respond to fungivores attack via HKs are not fully understood. In this study, we utilized Neurospora crassa to investigate the involvement of HKs in responding to fungivores attack. We found that the 11 HKs in N. crassa not only affected the growth and development, but also led to fluctuations in antioxidant production. Ten mutants in the genes encoding HKs (except ∆phy1) showed increased production of reactive oxygen species (ROS), especially upon Sinella curviseta attack. The ROS burst triggered changes in conidia and perithecial beaks formation, as well as accumulation of β-glucan, ergothioneine, ergosterol, and carotenoids. β-glucan was increased in ∆hk9, ∆os1, ∆hcp1, ∆nik2, ∆sln1, ∆phy1 and ∆phy2 mutants compared to the wild-type strain. In parallel, ergothioneine accumulation was improved in ∆phy1 and ∆hk16 mutants and further increased upon attack, except in ∆os1 and ∆hk16 mutants. Additionally, fungivores attack stimulated ergosterol and dehydroergosterol production in ∆hk9 and ∆os1 mutants. Furthermore, deletion of these genes altered carotenoid accumulation, with wild-type strain, ∆hk9, ∆os1, ∆hcp1, ∆sln1, ∆phy2, and ∆dcc1mutants showing an increase in carotenoids upon attack. Taken together, HKs are involved in regulating the production of conidia and antioxidants. Thus, HKs may act as sensors of fungivores attack and effectively improve the adaptive capacity of fungi to environmental stimuli., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Cardamine violifolia is a significant Brassicaceae plant known for its high selenium (Se) accumulation capacity, serving as an essential source of Se for both humans and animals. WRKY transcription factors play crucial roles in plant responses to various biotic and abiotic stresses, including cadmium stress, iron deficiency, and Se tolerance. However, the molecular mechanism of CvWRKY in Se accumulation is not completely clear., Results: In this study, 120 WRKYs with conserved domains were identified from C. violifolia and classified into three groups based on phylogenetic relationships, with Group II further subdivided into five subgroups. Gene structure analysis revealed WRKY variations and mutations within the CvWRKYs. Segmental duplication events were identified as the primary driving force behind the expansion of the CvWRKY family, with numerous stress-responsive cis-acting elements found in the promoters of CvWRKYs. Transcriptome analysis of plants treated with exogenous Se and determination of Se levels revealed a strong positive correlation between the expression levels of CvWRKY034 and the Se content. Moreover, CvWRKY021 and CvWRKY099 exhibited high homology with AtWRKY47, a gene involved in regulating Se accumulation in Arabidopsis thaliana. The WRKY domains of CvWRKY021 and AtWRKY47 were highly conserved, and transcriptome data analysis revealed that CvWRKY021 responded to Na 2 SeO 4 induction, showing a positive correlation with the concentration of Na 2 SeO 4 treatment. Under the induction of Na 2 SeO 3 , CvWRKY021 and CvWRKY034 were significantly upregulated in the roots but downregulated in the shoots, and the Se content in the roots increased significantly and was mainly concentrated in the roots. CvWRKY021 and CvWRKY034 may be involved in the accumulation of Se in roots., Conclusions: The results of this study elucidate the evolution of CvWRKYs in the C. violifolia genome and provide valuable resources for further understanding the functional characteristics of WRKYs related to Se hyperaccumulation in C. violifolia., (© 2024. The Author(s).)

With the acceleration of population aging, disability in older adults is a growing public health problem; however, little is known about the role of specific leisure-time activities in affecting disability. This study prospectively examined the association of leisure-time activities with disability among the Chinese oldest old. A total of 14 039 adults aged 80 years or older (median age of 89.8 years) were enrolled from the Chinese Longitudinal Healthy Longevity Survey from 1998 to 2014. Disability was defined as the presence of concurrent impairment in activities of daily living and physical performance. Cox proportional hazards models were used to estimate the associations between leisure-time activities and disability. During a mean of 4.2 years (2.7 years) of follow-up, 4487 participants developed disability. Compared with participants who never engaged in leisure-time activities, participants who engaged in almost daily activities, including gardening, keeping domestic animals or pets, playing cards or mahjong, reading books or newspapers, and watching TV or listening to the radio had a lower risk of disability, with HRs of 0.78 (0.69-0.88), 0.64 (0.58-0.70), 0.74 (0.63-0.86), 0.74 (0.65-0.84), and 0.84 (0.77-0.90), respectively. Moreover, the risk of disability gradually decreased with participation in an increasing number of those leisure-time activities (P for trend <0.001). Frequent engagement in leisure-time activities was associated with a lower risk of disability among the Chinese oldest old. This study highlights the importance of incorporating a broad range of leisure-time activities into the daily lives of older adults., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Public Health Association.)

Objectives: This study aimed to compare the accuracy of digital complete-arch implant impressions with prefabricated aids using three intraoral scanners (IOSs) and explore the correlation between virtual deviation measurement and physical framework misfit., Materials and Methods: Four edentulous maxillary master models with four and six parallel and angular implants were fabricated and scanned by a laboratory scanner as reference scans. Ten scans of each master model were acquired using three IOSs (IOS-T, IOS-M, and IOS-A) with and without prefabricated aids. Trueness and precision of root mean square (RMS) errors were measured. Ten aluminum alloy frameworks were fabricated, and the misfit was measured with a micro-computed tomography scan with one screw tightened., Results: Trueness and precision showed significant improvement when prefabricated aids were used for all three IOSs (p < 0.010). Median (interquartile range) RMS errors of trueness reduced from 67.5 (30.4) to 61.8 (30.3) μm, from 100.6 (35.4) to 45.9 (15.1) μm, and from 52.7 (33.2) to 41.1 (22.5) μm for scanner IOS-T, IOS-M, and IOS-A, respectively (p < 0.010). The precision of IOS-A and IOS-M was significantly better than IOS-T when using prefabricated aid (p < 0.001). RMS errors and the maximum marginal misfit of the framework were significantly correlated (p < 0.001, R 2  = 0.845)., Conclusions: With the prefabricated aids, the accuracy of IOSs enhanced significantly in digital complete-arch implant impressions. Three IOSs showed different levels of improvement in accuracy. Virtual RMS errors <62.2 μm could be the clinically acceptable threshold (150 μm) for framework passive fit., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Increasing evidence has shown that environmental factors play a crucial role in the pathogenesis of periodontitis. Humans are simultaneously exposed to a variety of environmental brominated flame retardants (BFRs). However, the relationship between BFRs in periodontitis remains unclear. This study aimed to investigate the overall association between BFRs and periodontitis in a nationally representative US population and to further identify important chemicals., Methods: Data from 3322 NHANES participants from 2009 to 2016 were used. Serum BFRs were registered, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE100, PBDE-153, PBDE-154, PBDE-183, PBDE-209 and PBB-153. Survey weighted generalized logistic regression models, restricted cubic splines (RCS) were conducted to assess single BFRs exposure with periodontitis. Meanwhile, weighted quantile sum (WQS) regression and Bayesian kernel machine regression (BKMR) were used to evaluate the overall association of BFRs mixtures with periodontitis and to identify significant chemicals., Results: A total of 3322 participants were included in the study, of whom 1795 had periodontitis. After adjusting for potential confounders, multiple logistic regression analysis revealed significant positive associations between serum levels of PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153 and the risk of periodontitis (all P < 0.05). A dose-response relationship was observed for many of these BFRs, with higher quantiles associated with an increased risk of periodontitis. WQS regression identified PBDE-183 (38.60%), PBDE-153 (21.20%), PBDE-209 (14.40%), and PBDE-99 (11.90%) as the BFRs with the largest weights contributing to the overall mixture effect on periodontitis risk. BKMR analysis further supported the positive association between serum BFRs and periodontitis, with most individual BFRs showing a positive trend, except for PBDE-153. Restricted cubic spline analysis revealed a generally increasing probability of periodontitis with increasing concentrations of BFRs, albeit with some nonlinear patterns for certain compounds., Conclusion: In conclusion, this study provides compelling evidence of a significant association between exposure to brominated flame retardants (BFRs) and an increased risk of periodontitis in a nationally representative sample of U.S. adults. Elevated serum levels of several BFRs, including PBDE-28, PBDE-47, PBDE-85, PBDE-99, PBDE-100, PBDE-154, PBDE-183, and PBB-153, were found to be positively associated with periodontitis, exhibiting a dose-response relationship., Competing Interests: Declaration of competing interest The authors declare that they have no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Blood-brain barrier (BBB) disruption is increasingly recognized as an early contributor to the pathophysiology of cerebral ischemia/reperfusion (I/R) injury, and is also a key event in triggering secondary damage to the central nervous system. Recently, long non-coding RNA (lncRNA) have been found to be associated with ischemic stroke. However, the roles of lncRNA in BBB homeostasis remain largely unknown. Here, we report that long intergenic non-coding RNA-p21 (lincRNA-p21) was the most significantly down-regulated lncRNA in human brain microvascular endothelial cells (HBMECs) after oxygen and glucose deprivation/reoxygenation (OGD/R) treatment among candidate lncRNA, which were both sensitive to hypoxia and involved in atherosclerosis. Exogenous brain-endothelium-specific overexpression of lincRNA-p21 could alleviate BBB disruption, diminish infarction volume and attenuate motor function deficits in middle cerebral artery occlusion/reperfusion (MCAO/R) mice. Further results showed that lincRNA-p21 was critical to maintain BBB integrity by inhibiting the degradation of junction proteins under MCAO/R and OGD/R conditions. Specifically, lincRNA-p21 could inhibit autophagy-dependent degradation of occludin by activating PI3K/AKT/mTOR signaling pathway. Besides, lincRNA-p21 could inhibit VE-cadherin degradation by binding with miR-101-3p. Together, we identify that lincRNA-p21 is critical for BBB integrity maintenance, and endothelial lincRNA-p21 overexpression could alleviate cerebral I/R injury in mice, pointing to a potential strategy to treat cerebral I/R injury., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

As ethnic medicine, the whole grass of plants in Cirsium was used as antimicrobial. This review focuses on the antimicrobial activity of plants in Cirsium, including antimicrobial components, against different types of microbes and bacteriostatic mechanism. The results showed that the main antimicrobial activity components in Cirsium plants were flavonoids, triterpenoids and phenolic acids, and the antimicrobial ability varied according to the species and the content of chemicals. Among them, phenolic acids showed a strong antibacterial ability against Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterococcus faecium. The antibacterial mechanisms include: (1) damaging the cell membrane, cell walls, mitochondria and nucleus of bacteria; (2) inhibiting the synthesis of proteins and nucleic acids; (3) suppressing the synthesis of enzymes for tricarboxylic acid cycle pathways and glycolysis, and then killing the bacteria via inhibition of energy production. Totally, most research results on antimicrobial activity of Cirsium plants are reported based on in vitro assays. The evidence from clinical data and comprehensive evaluation are needed., (© 2024. The Chinese Journal of Integrated Traditional and Western Medicine Press and Springer-Verlag GmbH Germany, part of Springer Nature.)

While spatial and time-resolved anti-counterfeiting technologies have gained increasing attention owing to their excellent tunable photoluminescence, achieving high-security-level anti-counterfeiting remains a challenge. Herein, we developed a spatial-time-dual-resolved anti-counterfeiting system using zero-dimensional (0D) organic-inorganic Mn(II) metal halides: (EMMZ) 2 MnBr 4 (named M-1, EMMZ=1-Ethyl-3-Methylimidazolium Bromide) and (EDMMZ) 2 MnBr 4 (named M-2, EDMMZ=1-Ethyl-2,3-Dimethylimidazolium Bromide). M-1 shows a bright green emission with a quantum yield of 78 %. It undergoes a phase transformation from the crystalline to molten state with phosphorescence quenching at 350 K. Reversible phase and luminescent conversion was observed after cooling down for 15 s. Notably, M-2 exhibits green light emission similar to M-1 but undergoes phase conversion and phosphorescence quenching at 390 K, with reversible conversion observed after cooling down for 5 s. The photoluminescence switching mode of on(green)-off-on(green) can be achieved by temperature control, demonstrating excellent performance with short response times and ultra-high cyclic reversibility. By leveraging the different quenching temperatures and reversible PL conversion times of M-1 and M-2, we propose a spatial-time-dual-resolved photoluminescence (PL) switching system that combines M-1 and M-2. This system enables multi-fold tuning of the PL switch for encryption and decryption through cationic engineering strategies by modulating temperature and cooling time. This work presents a novel and feasible design strategy for advanced-level anti-counterfeiting technology based on a spatial-time-dual-resolved system., 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.)

For texture control in plant-meat alternatives, the interrelationship between apparent characteristics and chemical bonds in high-fiber formulations remains unclear. The influence of mulberry leaf powder on apparent characteristics and chemical bonds of raw materials, block and strip products at addition amounts of 0.5-25% was analyzed. The results showed that 8% addition significantly increased the chewiness of the block by 98.12%. The strips' texture shows a downward trend, and the processing produced more redness and color difference. Additives promoted the formation of voids, lamellar and filamentous structures, and the strip produced more striped structures. Disulfide bonds significantly increased in the block, and the β-turn in the secondary structure enhanced by 12.20%. The β-turn transformed into a β-sheet in strips. Principal component analysis revealed that the texture improvement was associated with producing disulfide bonds and β-turn, providing a basis for high-fiber components to improve products' apparent characteristics by chemical bonds., 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 the paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Acute kidney injury (AKI) is a prevalent and potentially life-threatening complication characterized by a high incidence and mortality. A large number of studies have emphasized the role of ferroptosis in AKI. Moreover, FBXW7, a ubiquitin ligase, has been implicated in acute organ injury. Analysis of the GEO database (GSE98622) revealed increased FBXW7 mRNA levels in the kidney following ischemia‒reperfusion (IR). However, the role of FBXW7 in AKI has not been elucidated. Therefore, this study aimed to investigate the role of FBXW7 in IR-AKI and its underlying mechanisms. Here, we found that IR could induce AKI and increase FBXW7 expression, while the ferroptosis inhibitor Fer-1 alleviated AKI and decreased FBXW7 expression. Furthermore, we treated HK-2 cells with hypoxia for 12 h and reoxygenation for 4 h (H12R4) to simulate IR-AKI and investigated the impact of modulating FBXW7 expression on ferroptosis by employing ferroptosis-related agonists or inhibitors. Our findings revealed that H12R4 induced HK2 ferroptosis and increased the expression of FBXW7. FBXW7 overexpression in control cells exacerbated erastin-induced ferroptosis, and FBXW7 knockdown inhibited ferroptosis in H12R4-treated cells. Mechanistically, we confirmed that FBXW7 can bind to GPX4, a key molecule that inhibits ferroptosis. The half-life of the GPX4 protein decreased after FBXW7 overexpression, GPX4 ubiquitination increased after H12R4, and GPX4 degradation decreased after FBXW7 knockdown. In conclusion, our results indicated that FBXW7 plays an important role in the development of IR-AKI by promoting ferroptosis through the downregulation of GPX4 expression. This study provides new insight into FBXW7 as a potential target for treating AKI., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background and Objective: Breast cancer is a leading cause of morbidity and mortality among women worldwide. This study aimed to assess the global burden of breast cancer and identify attributable risk factors across 204 countries and territories from 1990 to 2021., Methods: Using data from the Global Burden of Disease Study 2021, we analyzed the incidence, mortality, disability-adjusted life years (DALYs), and risk factors associated with breast cancer. We obtained and analyzed the age-standardized incidence rate (ASIR), age-standardized death rate (ASDR), and age-standardized DALYs rate from 1990 to 2021. We assessed geographical variations and the impact of the Socio-demographic Index (SDI) using regression analysis and stratification by SDI quintiles. Additionally, we estimated the risk factors attributable to breast cancer deaths and DALYs using the comparative risk assessment framework of the GBD study., Results: Globally, breast cancer incident cases increased from 875,657 in 1990 to 2,121,564 in 2021. The ASIR rose from 16.42 to 26.88 per 100,000 (95% CI: 1.54-1.60). High SDI regions showed the highest ASIR (66.89 per 100,000 in 2021), while Low SDI regions had the lowest (6.99 per 100,000 in 2021). The global ASDR decreased from 10.42 to 8.54 per 100,000, and the age-standardized DALYs rate decreased from 313.36 to 261.5 per 100,000 between 1990 and 2021. However, these improvements were not uniform across SDI regions. Risk factors included high body-mass index, alcohol use, tobacco, and high fasting plasma glucose, with variations across SDI regions., Conclusion: The global burden of breast cancer has increased significantly from 1990 to 2021, with disparities observed across SDI regions. While high SDI areas show improvements in mortality and DALYs, lower SDI regions face increasing burdens. Targeted interventions addressing modifiable risk factors and improving healthcare access in less developed regions are crucial for reducing the global impact of breast cancer., (© 2024. The Author(s).)

Objective: The present study aimed to explore the potential causal relationship between childhood asthma and chronic obstructive pulmonary disease (COPD) in European and East Asian populations with Mendelian randomization (MR) analysis., Methods: Based on summary data from genome-wide association studies, single nucleotide polymorphisms (SNPs) associated with childhood asthma were used as instrumental variables. The MR analysis employed the inverse variance weighting, MR-Egger regression and weighted median method to estimate the causal effect between childhood asthma and COPD in European and East Asian populations. Cochran's Q test, MR-PRESSO method and MR-Egger intercept were used to detect heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis applied to assess the effect of removing individual SNP on the estimate of causal association., Results: The MR analysis showed no genetic causal relationship between childhood asthma and COPD. The results of Cochran's Q test, MR-PRESSO and MR-Egger regression indicated the absence of heterogeneity, outliers and horizontal pleiotropy, respectively. Leave-one-out analysis showed no significant difference in the statistical results after exclusion of single SNPs., Conclusions: The MR analysis revealed that there is no causal relationship between childhood asthma and COPD at the genetic level in both European and East Asian populations. Additionally, due to the presence of shared confounding factors and pathogenic genes, further research is needed to comprehensively assess the relationship between childhood asthma and COPD., Competing Interests: None., (© 2024 The Author(s).)

Recently the FDA conducted a risk investigation and labeled the Boxed Warning for all BCMA- and CD19-directed CAR-T cell therapy, so does it mean that the public must take risk of secondary cancer to receive cell therapy? Here, without lentivirus and professional antigen presenting cell application, a novel tumor-specific T-cell therapy was successfully developed only by co-culturing MHC + cancer cells and Naïve-T cells under the CD28 co-stimulatory signals. These tumor-specific T-cells could be separated through cell size and abundantly produced from peripheral blood, and would spontaneously attack target cells that carrying the same tumor antigen while avoiding others in vitro test. Moreover, it markedly decreased 90% tumor nodules companying with greatly improving overall survival (76 days vs 30 days) after twice infusion back to mice. This work maximally avoided the risks of secondary cancer and non-specific killing, and might open a revolutionary beginning of natural tumor-specific T-cell therapy., (© 2024. The Author(s).)

Background: Major depressive disorder (MDD) becomes one of the psychiatric disorders characteristic of a combination of cognitive, emotional, and somatic symptoms. Additionally, cognitive impairment has the most significant impact on functional results. However, the evaluation of cognitive level is still based on various subjective questionnaires as there is no objective standard assessment yet. This research focuses on resting-state alpha activity to identify cognition in MDD patients using electroencephalography (EEG) signals., Methods: Ninety-two subjects were recruited: 44 patients with MDD and 48 healthy individuals as controls. Functional outcome and cognition were assessed using standardized instruments, and the EEG resting state signal of open and closed eyes was recorded. The comparison and correlation of cognitive levels with alpha power in the bilateral frontal region, bilateral central region, bilateral occipital region, and middle line was evaluated., Results: The relative alpha power in MDD group was significantly lower than that in the control group (P < 0.05). Through correlation analysis, it was shown that the bilateral frontal and occipital alpha power of MDD patients in the closed-eyes state was positively correlated with information processing rate, verbal learning, working memory, and attention retention. The alpha power of the bilateral frontal region in the open-eyes state was positively correlated with information processing rate, working memory, and attention retention (P < 0.05)., Conclusion: The research indicates that the changes in frontal and occipital alpha activities may be a promising neurophysiological indicator of cognitive level to diagnose and treat response prediction., Competing Interests: The authors have no conflicts of interest to declare in this work., (© 2024 Xie et al.)