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Formate dehydrogenase (FDH) is widely applied in regeneration of redox cofactors. There are continuing interests to engineer FDH for improved catalytic activity and cofactor preference. In the crystal structure of FDH from Pseudomonas sp. 101 (pseFDH), the C terminus with 9 amino acid residues cannot be resolved. However, our earlier work showed mutations at C terminus led pseFDH variants to favor a non-natural cofactor nicotinamide cytosine dinucleotide (NCD). Here, we investigated the role of C-terminal residues on cofactor preference by truncating their corresponding C terminus of pseFDH variants. Sequence comparison analysis showed that C-terminal residues were barely conservative among different FDHs. pseFDH and mutants with their C termini truncated were constructed, and the resulted variants showed improved preference to NCD mainly because NAD-dependent activity dropped more substantially. Further structure analysis showed that these pseFDH variants had their cofactor binding domains reconstructed to favor molecular interactions with NCD. Our work indicated that C-terminal residues of pseFDH affected enzyme activity and cofactor preference, which provides a new approach for ameliorating the performance of redox enzymes., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Water scarcity is a significant constraint in agricultural ecosystems of arid regions, necessitating sustainable development of agricultural water resources. This study innovatively combines Bayesian theory and Water Footprint (WF) to construct a Bayesian Network (BN). Water quantity and quality data were evaluated comprehensively by WF in agricultural production. This evaluation integrates WF and local water resources to establish a sustainability assessment framework. Selected nodes are incorporated into a BN and continuously updated through structural and parameter learning, resulting in a robust model. Results reveal a nearly threefold increase of WF in the arid regions of Northwest China from 1989 to 2019, averaging 189.95 × 10 8  m 3 annually. The region's agricultural scale is expanding, and economic development is rapid, but the unsustainability of agricultural water use is increasing. Blue WF predominates in this region, with cotton having the highest WF among crops. The BN indicates a 70.1 % probability of unsustainable water use. Sensitivity analysis identifies anthropogenic factors as primary drivers influencing water resource sustainability. Scenario analysis underscores the need to reduce WF production and increase agricultural water supply for sustainable development in arid regions. Proposed strategies include improving irrigation methods, implementing integrated water-fertilizer management, and selecting drought-resistant, economically viable crops to optimize crop planting structures and enhance water use efficiency in current agricultural practices in arid regions. This study not only offers insights into water management in arid regions but also provides practical guidance for similar agricultural contexts. The BN model serves as a flexible tool for informed decision-making in dynamic environments., 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 B.V.)

Background: E-cigarettes have gained popularity among teenagers due to extensive marketing strategies on social media platforms. This widespread promotion is a risk factor, as it fosters more positive attitudes toward e-cigarette use among teenagers and increases the perception that using e-cigarettes is normal. Therefore, the marketing of e-cigarettes on social media is a serious global health concern, and its strategies and impact should be clearly identified., Objective: This study examined how e-cigarette companies popularize their products via Weibo and identified the specific strategies influencing the effectiveness of their marketing., Methods: In phase 1, we conducted a search on Qcc.com and identified 32 e-cigarette brands with active Weibo accounts between October 1 and December 31, 2020, along with 863 Weibo posts. The data were investigated through content analysis. The codebook was developed into four categories: (1) product and features, (2) sales and promotions, (3) social contact and interaction, and (4) restrictions and warnings. To further understand the factors influencing e-cigarette brand marketing, we conducted a multiple linear regression analysis., Results: Marketing tactics by e-cigarette companies on Chinese social media were documented, including emphasizing attractive product features, using trendy characters, implicit promotions, downplaying health concerns, and engaging with Weibo users in various ways. Out of 863 posts, 449 (52%) mentioned product characteristics. In 313 (36.3%) posts, visible figures were used to attract attention. Product promotion was absent in 762 (88.3%) posts, and purchase channels were not mentioned in 790 (98.3%) posts. Social interaction-related posts received attention (n=548, 63.5%), particularly those featuring hashtag content (n=538, 62.3%). Most posts did not include claims for restrictions on teenagers' purchases or use (n=687, 79.6%) or information on health warnings (n=839, 97.2%). Multiple linear regression analysis identified marketing strategies that effectively increase the exposure of e-cigarette posts on Weibo. Posts including engagement via posts encouraging reposts, comments, and likes (P<.001) and engagement topics related to e-cigarette brands were positively correlated with the number of reposts (P=.009). Posts highlighting nonmonetary incentives (P=.004), posts with age restriction statements (P<.001), engaging via stories and idea collection (P<.001), and engagement topics related to products (P<.001) and current affairs (P=.002) had a positive effect on the number of comments. Engagement topics related to brands (P<.001) or interactive sweepstakes (P<.001) had a positive effect on the number of likes., Conclusions: E-cigarette posts on Weibo that focus on product features and social interaction attract public attention, especially from teenagers. Stricter regulations and monitoring should be adopted to restrict the social media marketing of e-cigarettes., (©Xinyi Zhou, Xinyu Hao, Yuhang Chen, Hui Deng, Ling Fang, Lingyun Zhang, Xiaotao Yan, Pinpin Zheng, Fan Wang. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 07.11.2024.)

Background: Genomic screening uncovered interferon-gamma (IFNγ) pathway defects in tumours refractory to immune checkpoint blockade (ICB). However, its non-mutational regulation and reversibility for therapeutic development remain less understood., Objective: We aimed to identify ICB resistance-associated druggable histone deacetylases (HDACs) and develop a readily translatable combination approach for patients with hepatocellular carcinoma (HCC)., Design: We correlated the prognostic outcomes of HCC patients from a pembrolizumab trial (NCT03419481) with tumourous cell expressions of all HDAC isoforms by single-cell RNA sequencing. We investigated the therapeutic efficacy and mechanism of action of selective HDAC inhibition in 4 ICB-resistant orthotopic and spontaneous models using immune profiling, single-cell multiomics and chromatin immunoprecipitation-sequencing and verified by genetic modulations and co-culture systems., Results: HCC patients showing higher HDAC1 / 2 / 3 expressions exhibited deficient IFNγ signalling and poorer survival on ICB therapy. Transient treatment of a selective class-I HDAC inhibitor CXD101 resensitised HDAC1/2/3 high tumours to ICB therapies, resulting in CD8 + T cell-dependent antitumour and memory T cell responses. Mechanistically, CXD101 synergised with ICB to stimulate STAT1-driven antitumour immunity through enhanced chromatin accessibility and H3K27 hyperacetylation of IFNγ-responsive genes. Intratumoural recruitment of IFNγ + GZMB + cytotoxic lymphocytes further promoted cleavage of CXD101-induced Gasdermin E (GSDME) to trigger pyroptosis in a STAT1-dependent manner. Notably, deletion of GSDME mimicked STAT1 knockout in abolishing the antitumour efficacy and survival benefit of CXD101-ICB combination therapy by thwarting both pyroptotic and IFNγ responses., Conclusion: Our immunoepigenetic strategy harnesses IFNγ-mediated network to augment the cancer-immunity cycle, revealing a self-reinforcing STAT1-GSDME pyroptotic circuitry as the mechanistic basis for an ongoing phase-II trial to tackle ICB resistance (NCT05873244)., Competing Interests: Competing interests: The authors declare no conflicts of interest related to this work, except for the following declarations. SLC serves as an advisory member for AstraZeneca, MSD, Eisai, BMS, Ipsen and Hengrui, received research funds from MSD, Eisai, Ipsen, SIRTEX and Zailab, and honoraria from AstraZeneca, Eisai, Roche, Ipsen and MSD., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Due to the differences in photoresponse characteristics between photodetectors and neuromorphic vision sensors (NVS), simultaneously achieving these two powerful functionalities on a single device poses significant challenges. Here, we demonstrate a two-in-one platform based on a 28 × 28 β-Ga 2 O 3 array that seamlessly switches between photodetector and NVS modes via bias voltage control. By exploiting the differential carrier capture dynamics of deep-level oxygen vacancies in Ga 2 O 3 , our device exhibits conventional photoconductivity at low voltages and persistent photoconductivity at high voltages. This enables high-quality optoelectronic imaging as well as excellent image sensing, memory, and neuromorphic visual preprocessing capabilities within a single integrated platform. This work paves the way for multifunctional Ga 2 O 3 optoelectronic devices with applications in integrated sensing and computing.

The Tibetan Plateau's distinctive high-altitude environment, marked by extreme cold and reduced oxygen levels, presents considerable survival challenges for both humans and mammals. Natural selection has led to the accumulation of adaptive mutations in Tibetan pigs, enabling them to develop distinctive adaptive phenotypes. Here, we aim to uncover the genetic mechanisms underlying the adaptation of Tibetan pigs to high-altitude hypoxia. Therefore, we conducted a systematic analysis of 140 whole-genome sequencing (WGS) data points from different representing pig populations. Our analysis identified a total of 27,614,561 mutations, including 22,386,319 single-nucleotide variants (SNVs) and 5,228,242 insertions/deletions (INDELs, size < 50 bp). A total of 11% (2,678,569) of the SNVs were newly identified in our project, significantly expanding the dataset of genetic variants in Tibetan pigs. Compared to other pig breeds, Tibetan pigs are uniquely adapted to high-altitude environments, exhibiting the highest genetic diversity and the lowest inbreeding coefficient. Employing the composite of multiple signals (CMS) method, we scanned the genome-wide Darwinian positive selection signals and identified 32,499 Tibetan pig positively selected SNVs (TBPSSs) and 129 selected genes (TBPSGs), including 213 newly discovered genes. Notably, we identified eight genes ( PHACTR1 , SFI1 , EPM2A , SLC30A7 , NKAIN2 , TNNI3K , and PLIN2 ) with strong nature selection signals. They are likely to improve cardiorespiratory function and fat metabolism to help Tibetan pigs become adapted to the high-altitude environment. These findings provide new insights into the genetic mechanisms of high-altitude adaptation and the adaptive phenotypes of Tibetan pigs.

Objective: The goal was to analyse website content of Chinese electronic (e) cigarette manufacturing enterprises and understand the marketing strategies to provide evidence for decision-makers to regulate manufacturers., Methods: Through QCC.com, one of the largest enterprise information query platforms in China, we identified 104 official manufacturer websites in 2021. A codebook including 6 sections with 31 items was developed and all webpages were coded separately by two trained researchers., Results: Over half of the websites (56.7%) did not have age verification for entry. Thirty-two (30.8%) websites had no restriction for minors to use or purchase e-cigarettes, and 79 (76.0%) had no health warning. Overall, 99 websites (95.2%) displayed their products, and 72 (69.2%) displayed e-flavours. The most frequently used descriptions of products included good taste (68.3%), positive mood (62.5%), leakage resistance (56.7%), enjoyment (47.1%), reduced harm (45.2%), alternatives to cigarettes (43.3%) and long battery life (42.3%). Additionally, 75 websites (72.1%) provided contact information on different channels, including WeChat (59.6%), Weibo (41.3%), Facebook (13.5%), Instagram (12.5%) and brand apps (2.9%). Manufacturers provided investment and franchise information (59.6%) and offline store information (17.3%). In addition, 41.3% websites included content regarding corporate social responsibility., Conclusions: Chinese e-cigarette manufacturers' official websites have become a platform for presenting product and brand information, establishing online and offline marketing loops, and displaying corporate social responsibility with weak age restrictions on access and a lack of health warnings. The Chinese government should implement strict regulatory measures on e-cigarette enterprises., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Coronary heart disease (CHD) is one of the leading causes of mortality. The current study aims to assess the association between C-reactive protein-triglyceride glucose index (CTI) and the risk of prevalent CHD and to evaluate the usefulness of CTI to refine the identification of prevalent CHD., Methods: 19,451 subjects from the National Health and Nutrition Examination Survey 1999-2010 were enrolled. CHD was ascertained according to the questionnaire., Results: The prevalent of CHD was 6.23%. After adjusting for conventional cardiovascular risk factors, each SD increase of CTI could cast a 1.357 times risk of CHD. In quartile analysis, the top quartile had a 1.807 times risk of CHD than the bottom quartile. Smooth curving fitting displayed that the association was linear in the entire range of CTI. Subgroup analysis revealed that the association was robust among several common subpopulations but stronger in subjects aged <60. Finally, both ROC and reclassification analysis demonstrated a significant improvement in identifying CHD when introducing CTI to the Framingham risk score., Conclusion: CTI has a positive, linear, and robust association with prevalent CHD in the general American population, and CTI may help to improve the detection of prevalent CHD in the general population., 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 reviewer DW declared a shared parent affiliation with the author(s) WS to the handling editor at the time of review., (© 2024 Xu, Zhang, Xu, Shi and Zhang.)

Our previous study showed that pyridoxine 5'-phosphate oxidase (PNPO) is a tissue biomarker of ovarian cancer (OC) and has a prognostic implication but detailed mechanisms remain unclear. The current study focused on PNPO-regulated lysosome/autophagy-mediated cellular processes and the potential role of PNPO in chemoresistance. We found that PNPO was overexpressed in OC cells and was a prognostic factor in OC patients. PNPO significantly promoted cell proliferation via the regulation of cyclin B1 and phosphorylated CDK1 and shortened the G2M phase in a cell cycle. Overexpressed PNPO enhanced the biogenesis and perinuclear distribution of lysosomes, promoting the degradation of autophagosomes and boosting the autophagic flux. Further, an autolysosome marker LAMP2 was upregulated in OC cells. Silencing LAMP2 suppressed cell growth and induced cell apoptosis. LAMP2-siRNA blocked PNPO action in OC cells, indicating that the function of PNPO on cellular processes was mediated by LAMP2. These data suggest the existence of the PNPO-LAMP2 axis. Moreover, silencing PNPO suppressed xenographic tumor formation. Chloroquine counteracted the promotion effect of PNPO on autophagic flux and inhibited OC cell survival, facilitating the inhibitory effect of PNPO-shRNA on tumor growth in vivo. Finally, PNPO was overexpressed in paclitaxel-resistant OC cells. PNPO-siRNA enhanced paclitaxel sensitivity in vitro and in vivo. In conclusion, PNPO has a regulatory effect on lysosomal biogenesis that in turn promotes autophagic flux, leading to OC cell proliferation, and tumor formation, and is a paclitaxel-resistant factor. These data imply a potential application by targeting PNPO to suppress tumor growth and reverse PTX resistance in OC., (© 2024. The Author(s).)

Introduction: Supervision measures in China have designated offline retail as the only legal channel for the sale and advertising of e-cigarettes. Specialty stores, exclusively selling vaping devices and e-liquids, are professionally designed to showcase company images and provide the best examples of e-cigarette marketing strategies. The goal was to analyze the retail marketing practice of e-cigarette specialty stores and provide a scientific reference for future e-cigarette point-of-sale regulation., Methods: On-site observations were conducted in specialty stores among the popular business districts of Chengdu and Shanghai, China, from January to May 2021. 'Dianping', known as 'Chinese Yelp', was used to identify 8 business districts in Shanghai and 5 in Chengdu as observation sites. Two trained observers visited each store in the identified business districts. The data were collected with a checklist, which consisted of 5 sections with 37 items, including basic information, marketing practice, age restriction and health warnings., Results: In total, 161 e-cigarette specialty stores, including 82 specialty stores in Shanghai and 79 in Chengdu, were identified. Of these stores, 156 were single-brand retailers and 5 were multi-brand retailers. Each store displayed e-cigarette products, which were visible from outside the store. The most common e-cigarette products were rechargeable kits and nicotine-containing e-liquids, which were available at all specialty stores. Frequent forms of promotion were free e-liquid samples (100%) and slogans (57.8%). Signage stating prohibition of minor use and purchase was presented at 141 (87.6%) specialty stores. Relatively few specialty stores (31.7%) displayed health warnings., Conclusions: E-cigarette specialty stores featured highly visible product displays, varied product selections, abundant marketing materials, free trial services, absent entry restrictions for minors, and a lack of health warnings. Policymakers should move to reduce youth exposure to e-cigarette products and marketing in the retail environment by strengthening regulations on product display and marketing., Competing Interests: The authors have each completed and submitted an ICMJE form for disclosure of potential conflicts of interest. The authors declare that they have no competing interests, financial or otherwise, related to the current work. All the authors report that since the initial planning of the work, this study was supported by the Bloomberg Initiative to Reduce Tobacco Use (CHINA-26-12), the National Natural Science Foundation of China (#82173635), and Shanghai Municipal Health Commission ‘Shanghai Three-year Action Plan to Strengthen the Construction of Public Health System (2023-2025)’ (GW VI-6)., (© 2024 Deng H. et al.)

Background: Colorectal cancer is the third most common cancer and the second leading cause of cancer death. There are limited therapeutic options for the treatment of locally advanced or metastatic colorectal cancers which fail first-line chemotherapy. Phase I/II studies showed that the combined application of the raltitrexed and irinotecan has significant synergistic effect and acceptable toxicity. However, most of these previous studies have relatively small sample size., Methods: This is a prospective open-label, single-arm, multi-center, Phase II trial. Brief inclusion criteria: patients were aged 18 to 75 years with locally advanced or metastatic colorectal cancer after failure of 5-FU and oxaliplatin therapy. Enrolled patients received raltitrexed (3 mg/m 2 , d1) and irinotecan (180 mg/m 2 , d1) each 21-day cycle until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, and the secondary endpoints were disease control rate, objective response rate, overall survival and safety., Results: A total of 108 patients were enrolled between September 2016 and May 2020. The median age was 61 years, ECOG 1 score accounts for 67.6%, the rest were ECOG 0. A total of 502 cycles were completed, with an average of 4.6 cycles and a median of 4 cycles. 108 patients were evaluated, with an objective response rate of 17.6%, and disease control rate of 76.9%. The median follow-up time was 27 months (range:3.1-61.0 m) at data cut-off on March 2023. Median progression-free survival was 4.9 months (95% CI 4.1-5.7) and median overall survival was 13.1 months (95% CI 12.2-15.5). The most common adverse events that were elevated are alanine aminotransferase increased, aspartate aminotransferase increased, fatigue, diarrhoea, neutrocytopenia, thrombocytopenia, hypohemoglobin, and leukocytopenia. Most of the adverse events were Grade I/II, which were relieved after symptomatic treatment, and there were no treatment-related cardiotoxicities and deaths., Conclusions: The combination of raltitrexed and irinotecan as second-line treatment for mCRC could be a reliable option after failure of standard 5-Fu-first-line chemotherapy in locally advanced or metastatic colorectal cancers, especially for patients with 5-FU intolerance (cardiac events or DPD deficiency patients)., Trial Registration: ClinicalTrials.gov identifier: NCT03053167, registration date was 14/2/2017., (© 2024. The Author(s).)

Here, a photoelectrochemical (PEC) immunosensor based on the FJU-200@CdSe heterostructure was developed for epidermal growth factor receptor (EGFR) detection. This is the first application of FJU-200 in PEC. After modification using CdSe quantum dots (QDs), FJU-200 and CdSe QDs formed an S-scheme heterostructure due to the interleaved energy band structure and the difference in Fermi energy (Ef) levels, which generated an efficient and stable PEC signal. When EGFR bound specifically to the antibody, a large spatial site resistance was generated, which hindered the electron transfer at the interface and the PEC signal was quenched. The proposed PEC sensing platform exhibited excellent detection performance for EGFR, with a good linear relationship with the photocurrent change value (ΔI) in the detection range of 10 fg/mL-100 ng/mL, and the detection limit was as low as 1.08 fg/mL. This work illustrates the potential electron transfer pathway between FJU-200 and CdSe QDs and creatively applies to the construction of PEC immunosensors, providing a new option for the detection of EGFR as well as other substances to be tested., 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.)

Purpose: The assessment of sarcoma during clinical practice is primarily based on imaging examination, with no effective biomarkers available. Although it has been established that 1,25(OH) 2 D 3 is abnormally expressed in patients with sarcoma, it remains unclear whether 1,25(OH) 2 D 3 level could be used as an evaluation marker in these patient population., Methods: This real-world study investigated 1,25(OH) 2 D 3 level and its association with clinical features in sarcoma patients. Data on 1,25(OH) 2 D 3 , parathyroid hormone, calcium, and calcitonin were collected from 331 patients with sarcoma, while the imaging results and the variation in 1,25(OH) 2 D 3 among 213 patients with sarcoma before and after treatment was further analyzed., Results: We found that the serum 1,25(OH) 2 D 3 level was predominantly decreased in patients with sarcoma, with a mean of 45.68 nmol/L. 1,25(OH) 2 D 3 was significantly correlated with the gender and age of sarcoma patients, with more substantial reductions in women and younger patients. Among sarcoma patients, those with progressive disease exhibited a 7.08 nmol/L (-13.73%) decrease in serum 1,25(OH) 2 D 3 levels compared to baseline, while patients with non-progressive disease showed a 1.11 nmol/L (+ 7.0%) increase., Conclusion: The variation of serum 1,25(OH) 2 D 3 can predict the disease status of patients with sarcoma. Decreased serum 1,25(OH) 2 D 3 levels are indicative of disease progression in sarcoma patients, suggesting its potential for application as a prognostic marker for disease assessment in this patient population., (© 2024. The Author(s).)

Background: Influenza B virus induced myocarditis is a rare complication with potentially wide variations in severity and clinical presentation, and the pathogenesis is unclear., Case Presentation: We describe a rare case of a 7-year-old boy who developed fulminant myocarditis (FM) due to influenza B virus infection. Treatment measures included mechanical ventilation, vasoactive agents, Extracorporeal membrane oxygenation (ECMO), Continuous Renal Replacement Therapy (CRRT), anti-inflammatory, antiviral, anti-infection, and enteral nutrition support. After 10 days of treatment, the patient succumbed to multiorgan failure., Conclusions: After a systematic review of the literature, we found that this disease predominantly affects females, with pediatric cases exceedingly rare. Fulminant myocarditis (FM) progresses rapidly, poses significant treatment challenges sporadic, and carries a poor prognosis. Interestingly, literature reports suggest that anti-thymocyte globulin therapy may have a positive impact in treating FM, potentially offering new insights into its pathogenesis and clinical management., (© 2024. The Author(s).)

The Qinghai-Tibet Plateau is a valuable genetic resource pool, and the high-altitude adaptation of Tibetan pigs is a classic example of the adaptive evolution of domestic animals. Here, we report the presence of Darwinian positive selection signatures in Tibetan pigs (TBPs) using 348 genome-wide datasets (127 whole-genome sequence datasets (WGSs) and 221 whole-genome single-nucleotide polymorphism (SNP) chip datasets). We characterized a high-confidence list of genetic signatures related response to high-altitude adaptation in Tibetan pigs, including 4,598 candidate SNPs and 131 candidate genes. Functional annotation and enrichment analysis revealed that 131 candidate genes are related to multiple systems and organs in Tibetan pigs. Notably, eight of the top ten novel genes, RALB, NBEA, LIFR, CLEC17A, PRIM2, CDH7, GK5 and FAM83B, were highlighted and associated with improved adaptive heart functions in Tibetan pigs high-altitude adaptation. Moreover, genome-wide association analysis revealed that 29 SNPs were involved in 13 candidate genes associated with at least one adaptive trait. In particular, among the top ten candidate genes, CLEC17A is related to a reduction in hemoglobin (HGB) in Tibetan pigs. Overall, our study provides a robust SNP/gene list involving genetic adaptation for Tibetan pig high-altitude adaptation, and it will be a valuable resource for future Tibetan pig studies., (© 2024. The Author(s).)

In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients., (© 2024. The Author(s).)

Introduction: Youth e-cigarette (EC) use has rapidly increased in the last few years. It is crucial to identify the susceptible youth and prevent them from EC uptake. This study was conducted to investigate factors that affect youth susceptibility to EC use., Methods: This study employed a cross-sectional survey design, utilizing multi-center stratified cluster sampling method to select two junior high schools and two senior high schools in Shanghai, Guangzhou, and Chengdu. One-third of classes of each grade in the selected schools were involved in this survey. After obtaining the informed consent of parents, an anonymous and self-administered questionnaire was distributed to students. Questionnaire was designed based on the Ecological Models of Health Behavior. Associations between EC susceptibility and covariates were identified using multivariate logistic regression., Results: Among 2,270 students who had never vaped, 38.0% were susceptible to ECs. Logistic regression analysis identified factors on different levels affecting the susceptibility. Individual factors included senior high school students (OR = 1.34, 95% CI: 1.08-1.65), sensation seeker (OR = 1.11, 95%CI: 1.08-1.14), poor academic performance (OR = 1.24, 95% CI: 1.01-1.54), ever cigarette user (OR = 2.27, 95% CI: 1.29-4.01), unaware of the second-hand smoke from vaping (OR = 1.56, 95% CI: 1.25-1.96), agreeable with "I do not want to hang around vapers" (OR = 0.79, 95% CI: 0.64-0.97), agreeable with "ECs are more fashionable than cigarette" (OR = 2.50, 95% CI: 1.72-3.62) and favorable attitudes toward vaping (OR = 5.09, 95% CI: 3.78-6.85) were significantly associated with susceptibility to ECs. At interpersonal level, students who believe they would not be punished by parents for vaping increased susceptibility (OR = 1.27, 95% CI:1.01-1.59). At community level, exposure of EC advertising (OR = 1.81, 95% CI:1.46-2.25), exposure to hazard information (OR = 0.76, 95% CI: 0.59-0.97) and seeing vaping in daily life (OR = 2.11, 95% CI: 1.62-2.74), were statistically significantly associated with youth susceptibility to ECs., Conclusion: EC susceptibility was observed in a substantial proportion of adolescents who had never vaped, influenced by factors on different levels. This research underscores the urgent need for comprehensive intervention strategies to prevent the youth susceptibility to ECs., 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 Deng, Fang, Zhang, Li, Wang, Wang and Zheng.)

In the present study, the debatable prognostic value of Ki67 in patients with non-small cell lung cancer (NSCLC) was attributed to the heterogeneity between lung adenocarcinoma (LUAD) and lung squamous carcinoma (LUSC). Based on meta-analyses of 29 studies, a retrospective immunohistochemical cohort of 1479 patients from our center, eight transcriptional datasets and a single-cell datasets with 40 patients, we found that high Ki67 expression suggests a poor outcome in LUAD, but conversely, low Ki67 expression indicates worse prognosis in LUSC. Furthermore, low proliferation in LUSC is associated with higher metastatic capacity, which is related to the stronger epithelial-mesenchymal transition potential, immunosuppressive microenvironment and angiogenesis. Finally, nomogram model incorporating clinical risk factors and Ki67 expression outperformed the basic clinical model for the accurate prognostic prediction of LUSC. With the largest prognostic assessment of Ki67 from protein to mRNA level, our study highlights that Ki67 also has an important prognostic value in NSCLC, but separate evaluation of LUAD and LUSC is necessary to provide more valuable information for clinical decision-making in NSCLC., (© 2024 The Author(s). Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Immunotherapy is becoming increasingly important, but the overall response rate is relatively low in the treatment of gastric cancer (GC). The application of tumor mutational burden (TMB) in predicting immunotherapy efficacy in GC patients is limited and controversial, emphasizing the importance of optimizing TMB-based patient selection. By combining TMB and major histocompatibility complex (MHC) related hub genes, we established a novel TM-Score. This score showed superior performance for immunotherapeutic selection (AUC = 0.808) compared to TMB, MSI status, and EBV status. Additionally, it predicted the prognosis of GC patients. Subsequently, a machine learning model adjusted by the TM-Score further improved the accuracy of survival prediction (AUC > 0.8). Meanwhile, we found that GC patients with low TM-Score had a higher mutation frequency, higher expression of HLA genes and immune checkpoint genes, and higher infiltration of CD8 + T cells, CD4 + helper T cells, and M1 macrophages. This suggests that TM-Score is significantly associated with tumor immunogenicity and tumor immune environment. Notably, based on the RNA-seq and scRNA-seq, it was found that AKAP5, a key component gene of TM-Score, is involved in anti-tumor immunity by promoting the infiltration of CD4 + T cells, NK cells, and myeloid cells. Additionally, siAKAP5 significantly reduced MHC-II mRNA expression in the GC cell line. In addition, our immunohistochemistry assays confirmed a positive correlation between AKAP5 and human leukocyte antigen (HLA) expression. Furthermore, AKAP5 levels were higher in patients with longer survival and those who responded to immunotherapy in GC, indicating its potential value in predicting prognosis and immunotherapy outcomes. In conclusion, TM-Score, as an optimization of TMB, is a more precise biomarker for predicting the immunotherapy efficacy of the GC population. Additionally, AKAP5 shows promise as a therapeutic target for GC., 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.)

Pervaporation (PV), as an energy-efficient mixture separation technology, plays an important role in the chemical industry. In this work, no organic templates were needed to produce high-performance ZSM-5 membranes with an extremely low Si/Al ratio of 3.3 on α-Al 2 O 3 tubular supports using 100 nm nanoseeds. The effects of preparation parameters on the crystalline phase structures, micromorphologies, and PV separation performance of ZSM-5 membranes were comprehensively investigated. The results revealed that the Si/Al ratio of gels significantly affected both the Si/Al ratio and the crystal orientation of the final ZSM-5 membrane. The optimized ZSM-5 membrane with a thickness of 1.8 μm was utilized to dehydrate various organic solvents via PV, and the influence of the operating parameters on PV dehydration performance was evaluated and is described herein. Furthermore, the permeation behaviors of single gases and PV were examined using permeate molecules within a similar size range to reveal the PV mechanism of the ZSM-5 membrane. The results demonstrated that gas permeation followed Knudsen diffusion, while PV permeation was decreased with decreases in the affinity of molecules, revealing an adsorption-diffusion mechanism that dominated PV dehydration through the ZSM-5 membrane. Moreover, the as-synthesized ZSM-5 membrane had good water permselectivity for water/acetone (e.g., total flux = 1.03 kg/(m 2  h), α = 307) and for water/isopropanol (e.g., total flux = 1.49 kg/(m 2 h), α = 1070) mixtures compared with other membranes reviewed in the literature. The synthesized ZSM-5 membrane also exhibited excellent reproducibility, high stability, and attractive PV separation performance, demonstrating its significant potential application in the PV dehydration of organic solvents., 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.)

Seed development and yield depend on the transport and supply of sugar. However, an insufficient supply of nutrients from maternal tissues to embryos results in seed abortion and yield reduction in Camellia oleifera . In this study, we systematically examined the route and regulatory mechanisms of sugar import into developing C. oleifera seeds using a combination of histological observations, transcriptome profiling, and functional analysis. Labelling with the tracer carboxyfluorescein revealed a symplasmic route in the integument and an apoplasmic route for postphloem transport at the maternal-filial interface. Enzymatic activity and histological observation showed that at early stages [180-220 days after pollination (DAP)] of embryo differentiation, the high hexose/sucrose ratio was primarily mediated by acid invertases, and the micropylar endosperm/suspensor provides a channel for sugar import. Through Camellia genomic profiling, we identified three plasma membrane-localized proteins including CoSWEET1b, CoSWEET15, and CoSUT2 and one tonoplast-localized protein CoSWEET2a in seeds and verified their ability to transport various sugars via transformation in yeast mutants and calli. In situ hybridization and profiling of glycometabolism-related enzymes further demonstrated that CoSWEET15 functions as a micropylar endosperm-specific gene, together with the cell wall acid invertase CoCWIN9, to support early embryo development, while CoSWEET1b , CoSWEET2a , and CoSUT2 function at transfer cells and chalazal nucellus coupled with CoCWIN9 and CoCWIN11 responsible for sugar entry in bulk into the filial tissue. Collectively, our findings provide the first comprehensive evidence of the molecular regulation of sugar import into and within C. oleifera seeds and provide a new target for manipulating seed development., Competing Interests: There are no competing interests in this paper, and the authors do not have any possible conflict of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nanjing Agricultural University.)

Background: Myosteatosis is correlated with poor prognosis in some malignancies. The creatinine-to-cystatin ratio (CCR) is revealed to predict gastric cancer prognosis. However, the prognostic abilities of CCR and the combination of CCR and myosteatosis in patients with pancreatic cancer (PC) who underwent radical surgery remains unclear., Methods: The retrospective cohort study included 215 patients with PC who underwent radical surgery (January 2016-October 2021). Clinicopathological and serological data were collected on admission. Myosteatosis and other body composition indices were assessed by using computed tomography. The cutoff value of CCR was determined by using the Youden index. Risk factors responsible for poor overall survival (OS) and disease-free survival (DFS) were determined by the Cox proportional hazards model., Results: The myosteatosis group included 104 patients (average age, 61.3 ± 9.1 years). The best cutoff value for CCR was 1.09. CCR ≤ 1.09 was an independent predictive biomarker inversely corelated with OS (P = 0.036). Myosteatosis was an independent risk factor associated with OS and DFS (P = 0.032 and P = 0.004, respectively). Patients with concomitant myosteatosis and CCR ≤ 1.09 had the worst OS (P = 0.016)., Conclusions: Myosteatosis and CCR are prognostic biomarkers for survival in PC patients who underwent radical surgery. Patients with the coexistence of myosteatosis and CCR ≤ 1.09 deserve more attention., (© 2024. Society of Surgical Oncology.)

Background & Aims: Recent studies demonstrated the importance of fibrosis in promoting an immunosuppressive liver microenvironment and thereby aggressive hepatocellular carcinoma (HCC) growth and resistance to immune checkpoint blockade (ICB), particularly via monocyte-to-monocytic myeloid-derived suppressor cell (M-MDSC) differentiation triggered by hepatic stellate cells (HSCs). We thus aimed to identify druggable targets in these immunosuppressive myeloid cells for HCC therapy., Methods: M-MDSC signature genes were identified by integrated transcriptomic analysis of a human HSC-monocyte culture system and tumor-surrounding fibrotic livers of patients with HCC. Mechanistic and functional studies were conducted using in vitro -generated and patient-derived M-MDSCs. The therapeutic efficacy of a M-MDSC targeting approach was determined in fibrosis-associated HCC mouse models., Results: We uncovered over-expression of protein phosphatase 1 regulatory subunit 15A ( PPP1R15A ), a myeloid cell-enriched endoplasmic reticulum stress modulator, in human M-MDSCs that correlated with poor prognosis and ICB non-responsiveness in patients with HCC. Blocking TGF-β signaling reduced PPP1R15A expression in HSC-induced M-MDSCs, whereas treatment of monocytes by TGF-β upregulated PPP1R15A, which in turn promoted ARG1 and S100A8/9 expression in M-MDSCs and reduced T-cell proliferation. Consistently, lentiviral-mediated knockdown of Ppp1r15a in vivo significantly reduced ARG1 + S100A8/9 + M-MDSCs in fibrotic liver, leading to elevated intratumoral IFN-γ + GZMB + CD8 + T cells and enhanced anti-tumor efficacy of ICB. Notably, pharmacological inhibition of PPP1R15A by Sephin1 reduced the immunosuppressive potential but increased the maturation status of fibrotic HCC patient-derived M-MDSCs., Conclusions: PPP1R15A + M-MDSC cells are involved in immunosuppression in HCC development and represent a novel potential target for therapies., Impact and Implications: Our cross-species analysis has identified PPP1R15A as a therapeutic target governing the anti-T-cell activities of fibrosis-associated M-MDSCs (monocytic myeloid-derived suppressor cells). The results from the preclinical models show that specific inhibition of PPP1R15A can break the immunosuppressive barrier to restrict hepatocellular carcinoma growth and enhance the efficacy of immune checkpoint blockade. PPP1R15A may also function as a prognostic and/or predictive biomarker in patients with hepatocellular carcinoma., (© 2024 The Authors.)

Hepatocellular carcinoma (HCC) is a common malignancy worldwide. Herein, we investigated the role of nicotinamide mononucleotide (NMN) in HCC progression. HCC cells were treated with NMN (125, 250, and 500 μM), and then nicotinamide adenine dinucleotide (NAD + ) and NADH levels in HCC cells were measured to calculate NAD + /NADH ratio. Cell proliferation, apoptosis, autophagy and ferroptosis were determined. AMPK was knocked down to confirm the involvement of AMPK/mTOR signaling. Furthermore, tumor-inhibitory effect of NMN was investigated in xenograft models. Exposure to NMN dose-dependently increased NAD + level and NAD + /NADH ratio in HCC cells. After NMN treatment, cell proliferation was inhibited, whereas apoptosis was enhanced in both cell lines. Additionally, NMN dose-dependently enhanced autophagy/ferroptosis and activated AMPK/mTOR pathway in HCC cells. AMPK knockdown partially rescued the effects of NMN in vitro. Furthermore, NMN treatment restrained tumor growth in nude mice, activated autophagy/ferroptosis, and promoted apoptosis and necrosis in tumor tissues. The results indicate that NMN inhibits HCC progression by inducing autophagy and ferroptosis via AMPK/mTOR signaling. NMN may serve as a promising agent for HCC treatment., (© 2024 Wiley Periodicals LLC.)

Objective: The purpose of this study was to evaluate the association between the single nucleotide polymorphisms (SNPs) ( EGR3 rs1996147; EGR4 rs3813226, rs6747506; ERBB3 rs2292238; and ERBB4 rs707284, rs7560730) and the risk of schizophrenia (SZ) in a Chinese population. Materials and Methods: We conducted a case-control study, including 248 patients with SZ and 236 healthy controls matched for age and sex. The Mass-array platform was used to detect all the genotypes of the SNPs. Results: The results revealed that the EGR3 rs1996147 AA genotype was associated with borderline decreased SZ risk (AA vs. GG: adjusted OR = 0.43, 95% CI: 0.18-1.02, p = 0.06). However, no significant correlation was found between the other SNPs and overall SZ risk. Subgroup analysis also failed to show any significant association between all SNPs and the risk of SZ. Conclusion: In summary, this study revealed that the EGR3 rs1996147 AA genotype was associated with a borderline risk for SZ.

γδ T cells are evolutionarily conserved T lymphocytes that manifest unique antitumor efficacy independent of tumor mutation burden (TMB) and conventional human leukocyte antigen (HLA) recognition. However, the dynamic changes in their T cell receptor (TCR) repertoire during cancer progression and treatment courses remain unclear. Here, a comprehensive characterization of γδTCR repertoires are performed in thyroid cancers with divergent differentiation states through cross-sectional studies. The findings revealed a significant correlation between the differentiation states and TCR repertoire diversity. Notably, highly expanded clones are prominently enriched in γδ T cell compartment of dedifferentiated patients. Moreover, by longitudinal investigations of the γδ T cell response to various antitumor therapies, it is found that the emergence and expansion of the Vδ2 neg subset may be potentially associated with favorable clinical outcomes after post-radiotherapeutic immunotherapy. These findings are further validated at single-cell resolution in both advanced thyroid cancer patients and a murine model, underlining the importance of further investigations into the role of γδTCR in cancer immunity and therapeutic strategies., (© 2024 The Authors. Advanced Science published by Wiley‐VCH GmbH.)

Tea grey blight disease is one of the most destructive diseases that infects tea and is caused by the pathogen Pestalotiopsis theae (Sawada) Steyaert. L-theanine is a unique non-protein amino acid of the tea plant. Different concentrations of L-theanine exhibit significant inhibitory effects on the growth and sporulation ability of the pathogen causing tea grey blight disease. To understand the effect mechanism of L-theanine on P. theae , transcriptome profiling was performed on the pathogenic mycelium treated with three different concentrations of L-theanine: no L-theanine treatment (TH0), 20 mg/mL theanine treatment (TH2), and 40 mg/mL theanine treatment (TH4). The colony growths were significantly lower in the treatment with L-theanine than those without L-theanine. The strain cultured with a high concentration of L-theanine produced no spores or only a few spores. In total, 2344, 3263, and 1158 differentially expressed genes (DEGs) were detected by RNA-sequencing in the three comparisons, Th2 vs. Th0, Th4 vs. Th0, and Th4 vs. Th2, respectively. All DEGs were categorized into 24 distinct clusters. According to GO analysis, low concentrations of L-theanine primarily affected molecular functions, while high concentrations of L-theanine predominantly affected biological processes including external encapsulating structure organization, cell wall organization or biogenesis, and cellular amino acid metabolic process. Based on KEGG, the DEGs of Th2 vs. Th0 were primarily involved in pentose and glucuronate interconversions, histidine metabolism, and tryptophan metabolism. The DEGs of Th4 vs. Th0 were mainly involved in starch and sucrose metabolism, amino sugar, and nucleotide sugar metabolism. This study indicated that L-theanine has a significant impact on the growth and sporulation of the pathogen of tea grey blight disease and mainly affects amino acid metabolism, carbohydrate metabolism, and cellular structure-related biosynthesis processes of pathogenic fungi. This work provides insights into the direct control effect of L-theanine on pathogenic growth and also reveals the molecular mechanisms of inhibition of L-theanine to P. theae ., Competing Interests: The authors declare no conflicts of interest.

The NAC family of transcription factors (TFs) regulate plant development and abiotic stress. However, the specific function and response mechanism of NAC TFs that increase drought resistance in Picea wilsonii remain largely unknown. In this study, we functionally characterized a member of the PwNAC family known as PwNAC31 . PwNAC31 is a nuclear-localized protein with transcriptional activation activity and contains an NAC domain that shows extensive homology with ANAC072 in Arabidopsis . The expression level of PwNAC31 is significantly upregulated under drought and ABA treatments. The heterologous expression of PwNAC31 in atnac072 Arabidopsis mutants enhances the seed vigor and germination rates and restores the hypersensitive phenotype of atnac072 under drought stress, accompanied by the up-regulated expression of drought-responsive genes such as DREB2A (DEHYDRATION-RESPONSIVE ELEMENT BINDING PROTEIN 2A) and ERD1 (EARLY RESPONSIVE TO DEHYDRATION STRESS 1) . Yeast two-hybrid and bimolecular fluorescence complementation assays confirmed that PwNAC31 interacts with DREB2A and ABF3 (ABSCISIC ACID-RESPONSIVE ELEMENT-BINDING FACTOR 3). Yeast one-hybrid and dual-luciferase assays showed that PwNAC31, together with its interaction protein DREB2A, directly regulated the expression of ERD1 by binding to the DRE element of the ERD1 promoter. Collectively, our study provides evidence that PwNAC31 activates ERD1 by interacting with DREB2A to enhance drought tolerance in transgenic Arabidopsis .

The emerging cloud storage technology has significantly improved efficiency and productivity in the traditional electronic healthcare field. However, it has also brought about many security concerns. Ciphertext policy attribute-based encryption (CP-ABE) holds immense potential in achieving fine-grained access control, providing robust security for electronic healthcare data in the cloud. However, current CP-ABE schemes still face issues such as inflexible attribute revocation, relatively lower computational capabilities, and key management. To address these issues, this paper introduces a revocable and traceable undeniable ciphertext policy attribute-based encryption scheme (MA-RUABE). MA-RUABE not only enables fast and accurate data traceability, effectively preventing malicious user key leakage, but also includes a direct revocation feature, significantly enhancing computational efficiency. Furthermore, the introduction of a multi-permission mechanism resolves the issue of centralization of power caused by single-attribute permissions. Furthermore, a security analysis demonstrates that our system ensures resilience against chosen plaintext attacks. Experimental results demonstrate that MA-RUABE incurs lower computational overhead, effectively enhancing system performance and ensuring data-sharing security in cloud-based electronic healthcare systems.

Soil salinity is a major environmental factor constraining growth and productivity of highbush blueberry (Vaccinium corymbosum). Leaf Na+ content is associated with variation in salt tolerance among blueberry cultivars; however, the determinants and mechanisms conferring leaf Na+ exclusion are unknown. Here, we observed that the blueberry cultivar 'Duke' was more tolerant than 'Sweetheart' and accumulated less Na+ in leaves under salt stress conditions. Through transcript profiling, we identified a member of the high-affinity K+ transporter (HKT) family in blueberry, VcHKT1;1, as a candidate gene involved in leaf Na+ exclusion and salt tolerance. VcHKT1;1 encodes a Na+-preferential transporter localized to the plasma membrane and is preferentially expressed in the root stele. Heterologous expression of VcHKT1;1 in Arabidopsis (Arabidopsis thaliana) rescued the salt hypersensitivity phenotype of the athkt1 mutant. Decreased VcHKT1;1 transcript levels in blueberry plants expressing antisense-VcHKT1;1 led to increased Na+ concentrations in xylem sap and higher leaf Na+ contents compared with wild-type plants, indicating that VcHKT1;1 promotes leaf Na+ exclusion by retrieving Na+ from xylem sap. A naturally occurring 8-bp insertion in the promoter increased the transcription level of VcHKT1;1, thus promoting leaf Na+ exclusion and blueberry salt tolerance. Collectively, we provide evidence that VcHKT1;1 promotes leaf Na+ exclusion and propose natural variation in VcHKT1;1 will be valuable for breeding Na+-tolerant blueberry cultivars in the future., Competing Interests: Conflict of interest statement. None declared., (© American Society of Plant Biologists 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Advanced LUAD shows limited response to treatment including immune therapy. With the development of sequencing omics, it is urgent to combine high-throughput multi-omics data to identify new immune checkpoint therapeutic response markers. Using GSE72094 (n = 386) and GSE31210 (n = 226) gene expression profile data in the GEO database, we identified genes associated with lung adenocarcinoma (LUAD) death using tools such as "edgeR" and "maftools" and visualized the characteristics of these genes using the "circlize" R package. We constructed a prognostic model based on death-related genes and optimized the model using LASSO-Cox regression methods. By calculating the cell death index (CDI) of each individual, we divided LUAD patients into high and low CDI groups and examined the relationship between CDI and overall survival time by principal component analysis (PCA) and Kaplan-Meier analysis. We also used the "ConsensusClusterPlus" tool for unsupervised clustering of LUAD subtypes based on model genes. In addition, we collected data on the expression of immunomodulatory genes and model genes for each cohort and performed tumor microenvironment analyses. We also used the TIDE algorithm to predict immunotherapy responses in the CDI cohort. Finally, we studied the effect of PRKCD on the proliferation and migration of LUAD cells through cell culture experiments. The study utilized the TCGA-LUAD cohort (n = 493) and identified 2,901 genes that are differentially expressed in patients with LUAD. Through KEGG and GO enrichment analysis, these genes were found to be involved in a wide range of biological pathways. The study also used univariate Cox regression models and LASSO regression analyses to identify 17 candidate genes that were best associated with mortality prognostic risk scores. By comparing the overall survival (OS) outcomes of patients with different CDI values, it was found that increased CDI levels were significantly associated with lower OS rates. In addition, the study used unsupervised cluster analysis to divide 115 LUAD patients into two distinct clusters with significant differences in OS timing. Finally, a prognostic indicator called CDI was established and its feasibility as an independent prognostic indicator was evaluated by Cox proportional risk regression analysis. The immunotherapy efficacy was more sensitive in the group with high expression of programmed cell death models. Relationship between programmed cell death (PCD) signature models and drug reactivity. After evaluating the median inhibitory concentration (IC50) of various drugs in LUAD samples, statistically significant differences in IC50 values were found in cohorts with high and low CDI status. Specifically, Gefitinib and Lapatinib had higher IC50 values in the high-CDI cohort, while Olaparib, Oxaliplatin, SB216763, and Axitinib had lower values. These results suggest that individuals with high CDI levels are sensitive to tyrosine kinase inhibitors and may be resistant to conventional chemotherapy. Therefore, this study constructed a gene model that can evaluate patient immunotherapy by using programmed cell death-related genes based on muti-omics. The CDI index composed of these programmed cell death-related genes reveals the heterogeneity of lung adenocarcinoma tumors and serves as a prognostic indicator for patients., Competing Interests: The authors declare that they have no conflicts of interest to report regarding the present study., (© 2024 Liang et al.)

In this paper, an angular position sensor (APS) designed for a resonant miniaturized scanning mirror (M-SM) is presented. The APS operates based on the principle of differential variable capacitance, significantly expanding the detectable bandwidth from a few hertz to several kilohertz. By modeling the motion characteristics, the sampling rates of the biaxial scanning angles are 1473.6 times and 539.4 times higher than those of conventional sensors. Initially, the motion characteristics model is presented as a simple harmonic motion, converting sampled capacitance into continuous capacitance. Subsequently, the nonparallel state of the M-SM and sensor is transformed into a parallel state through the space coordinate system transformation. Furthermore, a 2D nonlinear angle transfer function is developed to convert the differential capacitance into an angle, thereby mitigating the nonlinear errors resulting from large angles. Achieving an accuracy better than 0.014°, the measuring range expands from ±0.5729° (±10 mrad) to ±5.026° ( ± 87 mrad). Additionally, the capturing mode and tracking mode are proposed to monitor real-time angular changes of the M-SM with an accuracy of 0.017°. High-precision APSs have enhanced beam pointing accuracy and resolution and can thereby be used to advance the development of laser components, including light detection and ranging (LiDAR)., Competing Interests: Conflict of interestThe authors declare no competing interests., (© The Author(s) 2023.)

Dendritic cells (DCs) are the most potent antigen-presenting cells in the human body. They detect and process environmental signals and communicate with T cells to bridge innate and adaptive immunity. Cell activation, function, and survival are closely associated with cellular metabolism. An increasing number of studies have revealed that lipid metabolism affects DC activation as well as innate and acquired immune responses. Combining lipid metabolic regulation with immunotherapy can strengthen the ability of antigen-presentation and T-cell activation of DCs, improve the existing anti-tumor therapy, and overcome the defects of DC-related therapies in the current stage, which has great potential in cancer therapy. This review summarizes the lipid metabolism of DCs under physiological conditions, analyzes the role of reprogramming the lipid metabolism of DCs in tumor immune regulation, and discusses potential immunotherapeutic strategies., 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 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

In this study, high-performance FAU (NaY type) zeolite membranes were successfully synthesized using small-sized seeds of 50 nm, and their gas separation performance was systematically evaluated. Employing nano-sized NaY seeds and an ultra-dilute reaction solution with a molar composition of 80 Na 2 O: 1Al 2 O 3 : 19 SiO 2 : 5000H 2 O, the effects of synthesis temperature, crystallization time, and porous support (α-Al 2 O 3 or mullite) on the formation of FAU membranes were investigated. The results illustrated that further extending the crystallization time or increasing the synthesis temperature led to the formation of a NaP impurity phase on the FAU membrane layer. The most promising FAU membrane with a thickness of 2.7 µm was synthesized on an α-Al 2 O 3 support at 368 K for 8 h and had good reproducibility. The H 2 permeance of the membrane was as high as 5.34 × 10 -7 mol/(m 2 s Pa), and the H 2 /C 3 H 8 and H 2 / i -C 4 H 10 selectivities were 183 and 315, respectively. The C 3 H 6 /C 3 H 8 selectivity of the membrane was as high as 46, with a remarkably high C 3 H 6 permeance of 1.35 × 10 -7 mol/(m 2 s Pa). The excellent separation performance of the membrane is mainly attributed to the thin, defect-free membrane layer and the relatively wide pore size (0.74 nm).

Background: Lung cancer (LC) is one of the most common malignancies globally. Besides early detection and surgical resection, there is currently no effective curative treatment for metastatic advanced LC. Exosomes are endogenous nano-extracellular vesicles produced by somatic cells that play an important role in the development and maintenance of normal physiology. Exosomes can carry proteins, peptides, lipids, nucleic acids, and various small molecules for intra- and intercellular material transport or signal transduction. LC cells can maintain their survival, proliferation, migration, invasion, and metastasis, by producing or interacting with exosomes. Basic and clinical data also show that exosomes can be used to suppress LC cell proliferation and viability, induce apoptosis, and enhance treatment sensitivity. Due to the high stability and target specificity, good biocompatibility, and low immunogenicity of exosomes, they show promise as vehicles of LC therapy., Conclusion: We have written this comprehensive review to communicate the LC treatment potential of exosomes and their underlying molecular mechanisms. We found that overall, LC cells can exchange substances or crosstalk with themselves or various other cells in the surrounding TME or distant organs through exosomes. Through this, they can modulate their survival, proliferation, stemness, migration, and invasion, EMT, metastasis, and apoptotic resistance., (© 2023. Springer Nature Switzerland AG.)

Despite tremendous efforts to exploit effective therapeutic strategies, most glioblastoma (GBM) inevitably relapse and become resistant to therapies, including radiotherapy and immunotherapy. The tumor microenvironment (TME) of recurrent GBM (rGBM) is highly immunosuppressive, dominated by tumor-associated macrophages (TAMs). TAMs consist of tissue-resident microglia and monocyte-derived macrophages (MDMs), which are essential for favoring tumor growth, invasion, angiogenesis, immune suppression, and therapeutic resistance; however, restricted by the absence of potent methods, the heterogeneity and plasticity of TAMs in rGBM remain incompletely investigated. Recent application of single-cell technologies, such as single-cell RNA-sequencing has enabled us to decipher the unforeseen diversity and dynamics of TAMs and to identify new subsets of TAMs which regulate anti-tumor immunity. Here, we first review hallmarks of the TME, progress and challenges of immunotherapy, and the biology of TAMs in the context of rGBM, including their origins, categories, and functions. Next, from a single-cell perspective, we highlight recent findings regarding the distinctions between tissue-resident microglia and MDMs, the identification and characterization of specific TAM subsets, and the dynamic alterations of TAMs during tumor progression and treatment. Last, we briefly discuss the potential of TAM-targeted strategies for combination immunotherapy in rGBM. We anticipate the comprehensive understanding of the diversity and dynamics of TAMs in rGBM will shed light on further improvement of immunotherapeutic efficacy in rGBM., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Zhang, Jiang, Zhang and Wei.)

Lung cancer (LC) incidence and mortality continue to increase annually worldwide. LC is insidious and readily metastasizes and relapses. Except for its early diagnosis and surgical resection, there is no effective cure for advanced metastatic LC, and the prognosis remains dismal. Exosomes, a class of nano-sized extracellular vesicles produced by healthy or diseased cells, are coated with a bilayer lipid membrane and contain various functional molecules such as proteins, lipids, and nucleic acids. They can be used for intracellular or intercellular signaling or the transportation of biological substances. A growing body of evidence supports that exosomes play multiple crucial roles in the occurrence and metastatic progression of many malignancies, including LC. The elucidation of the potential roles of exosomes in the initiation, invasion, and metastasis of LC and their underlying molecular mechanisms may contribute to improved early diagnosis and 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 © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

To elucidate the molecular mechanisms underlying the differential metabolism of albino (white), green, and purple pericarp coloration, biochemical profiling and transcriptome sequencing analyses were performed on three different tea pericarps, Zhongbaiyihao ( Camellia sinensis L. var. Zhongbai), Jinxuan ( Camellia sinensis L. var. Jinxuan), and Baitangziya ( Camellia sinensis L. var. Baitang). Results of biochemical analysis revealed that low chlorophyll content and low chlorophyll/carotene ratio may be the biochemical basis for albino characteristics in the 'Zhongbaiyihao' pericarp. The differentially expressed genes (DEGs) involved in anthocyanin biosynthesis, including DFR, F3'5'H, CCoAOMT, and 4-coumaroyl-CoA, were highly expressed in the purple 'Baitangziya' pericarp. In the chlorophyll synthesis of white pericarp, GUN5 (Genome Uncoupled 5) and 8-vinyl-reductase both showed high expression levels compared to the green one, which indicated that albino 'Zhongbaiyihao' pericarp had a higher chlorophyll synthesis capacity than 'Jinxuan'. Meanwhile, chlorophyllase (CLH, CSS0004684) was lower in 'Baitang' than in 'Jinxuan' and 'Zhongbaiyihao' pericarp. Among the differentially expressed transcription factors, MYB59, WRKY41-like2 (CS ng17509), bHLH62 like1 (CS ng6804), and bHLH62-like3 (CSS0039948) were downregulated in Jinxuan pericarp, suggesting that transcription factors played a role in regulating tea pericarp coloration. These findings provide a better understanding of the molecular mechanisms and theoretical basis for utilizing functional components of tea pericarp.

The Agrobacterium tumefaciens-mediated transformation for blueberries remains less efficient than is desirable. A new leaf callus regeneration and genetic transformation system was investigated in blueberries in this study. The leaf explants of cv. 'Legacy' and 'Northland' were used to establish the stable callus induction system when placed on the woody plant medium (WPM) supplemented with 1.0 mg·L -1 2, 4-D, 0.4 mg·L -1 6-BA for 30 d; then, the callus was sub-cultured in the proliferation medium supplemented with 1.5 mg·L -1 2, 4-D, 0.4 mg·L -1 6-BA in the darkness at 25 °C every 30 days. The co-cultivation of callus with A. tumefaciens was operated on WPM plus 100 μM acetosyringone for 4 days; then, the transferred callus was grown in WPM supplemented with 1.5 mg·L -1 2,4-D, 0.4 mg·L -1 6-BA, 50 mg·L -1 hygromycin, and 200 mg·L -1 cefotaxime. The VcCHS transgenic blueberry callus with both GFP signal and Hyg resistance was obtained from the transformed callus of cv. 'Northland'. The rate of GFP signal detected in the transformed callus was as high as 49.02%, which was consistent with the PCR assay. Collectively, this study provides a highly efficient genetic transformation system in blueberry callus and a powerful approach for the molecular breeding of blueberries.

Cascaded metasurfaces can exhibit powerful dynamic light manipulation by mechanically tuning the far-field interactions in the layers. However, in most current designs, the metasurfaces are separated by gaps smaller than a wavelength to form a total phase profile, representing the direct accumulation of the phase profiles of each layer. Such small gap sizes may not only conflict with the far-field conditions but also pose great difficulties for practical implementations. To overcome this limitation, a design paradigm taking advantage of a ray-tracing scheme that allows the cascaded metasurfaces to operate optimally at easily achievable gap sizes is proposed. Enabled by the relative lateral translation of two cascaded metasurfaces, a continuous two-dimensional (2D) beam-steering device for 1064 nm light is designed as a proof of concept. Simulation results demonstrate tuning ranges of ±45° for biaxial deflection angles within ±3.5 mm biaxial translations, while keeping the divergence of deflected light less than 0.007°. The experimental results agree well with theoretical predictions, and a uniform optical efficiency is observed. The  generializeddesign paradigm can pave a way towards myriad tunable cascaded metasurface devices for various applications, including but not limited to light detection and ranging (LiDAR) and free space optical communication., (© 2023 The Authors. Advanced Science published by Wiley-VCH GmbH.)

Purpose: Postoperative cancer recurrence and metastasis have always been huge challenges in cancer therapy. The concurrent cisplatin (CDDP)-based chemoradiotherapy regimen is a standard therapeutic strategy in some cancer treatments after surgical resection. However, severe side effects and unsatisfactory local tumor concentrations of CDDP have hampered the application of this concurrent chemoradiotherapy. Therefore, a superior option that can enhance CDDP-based chemoradiotherapy efficacy with milder concurrent therapy-related toxicity is highly desirable., Methods and Materials: We developed a platform based on fibrin gel (Fgel) loaded with CDDP to be implanted into the tumor bed after surgery combined with concurrent radiation therapy for the prevention of postoperative local cancer recurrence and distant metastasis. The postoperative subcutaneous tumor mouse models established by incomplete resection of primary tumors were used to evaluate the therapeutic advantages of this chemoradiotherapy regimen for postsurgical treatment., Results: The local and sustained release of CDDP from Fgel could enhance the antitumor efficacy of radiation therapy in the residual tumor with lower systemic toxicity. The therapeutic benefits of this approach are demonstrated in breast cancer, anaplastic thyroid carcinoma, and osteosarcoma mouse models., Conclusions: Our work offers a general platform for concurrent chemoradiotherapy to prevent postoperative cancer recurrence and metastasis., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Sugar transport from the source leaf to the sink organ is critical for seed development and crop yield, as well as for responding to abiotic stress. SWEETs (sugar will eventually be exported transporters) mediate sugar efflux into the reproductive sink and are therefore considered key candidate proteins for sugar unloading during seed development. However, the specific mechanism underlying the sugar unloading to seeds in Camellia oleifera remains elusive. Here, we identified a SWEET gene named CoSWEET10, which belongs to Clade III and has high expression levels in the seeds of C. oleifera . CoSWEET10 is a plasma membrane-localized protein. The complementation assay of CoSWEET10 in SUSY7/ura3 and EBY.VW4000 yeast strains showed that CoSWEET10 has the ability to transport sucrose, glucose, and fructose. Through the C. oleifera seeds in vitro culture, we found that the expression of CoSWEET10 can be induced by hexose and sucrose, and especially glucose. By generating the restoration lines of CoSWEET10 in Arabidopsis atsweet10 , we found that CoSWEET10 restored the seed defect phenotype of the mutant by regulating soluble sugar accumulation and increased plant drought tolerance. Collectively, our study demonstrates that CoSWEET10 plays a dual role in promoting seed development and enhancing plant drought resistance as a sucrose and hexose transporter.

Environmentally persistent free radicals (EPFRs) in PM 2.5 can pose significant health risks by generating reactive oxygen species (ROS). In this study, Beijing and Yuncheng were chosen as two representative northern cities of China that mainly relied on natural gas and coal respectively as the energy source for domestic heating in winter. The pollution characteristics and exposure risks of EPFRs in PM 2.5 around the heating season of 2020 were investigated and compared between the two cities. Through laboratory simulation experiments, the decay kinetics and secondary formation of EPFRs in PM 2.5 collected in both cities were also studied. EPFRs in PM 2.5 collected in Yuncheng in the heating period showed longer lifetime and lower reactivity, suggesting that EPFRs originated from coal combustion were more stable in the atmosphere. However, the generation rate of hydroxyl radical (·OH) by the newly formed EPFRs in PM 2.5 in Beijing under ambient conditions was 4.4 times of that in Yuncheng, suggesting higher oxidative potential of EPFRs from the atmospheric secondary processes. Accordingly, the control strategies of EPFRs and their health risks were raised for the two cities, which would also have direct implication for the control of EPFRs in other areas of similar atmospheric emission and reaction patterns., 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. Competing interests The authors declare that they have no conflict of interest., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Introduction: Human papillomavirus (HPV) infection, an important pathogenic factor for cervical cancer, can be prevented by the HPV vaccine. Health care provider (HCP) recommendations contribute to improve HPV vaccination coverage. The aim of this study was to assess the frequency of HCP recommendations for HPV vaccination and associated factors., Methods: From Nov 8 to Dec 6 in 2018, a cross-sectional study was conducted through online questionnaires among HCPs ( n  = 1,371) from hospitals in three large cities in China (Shanghai, Guangzhou, and Shenzhen). Data on demographic characteristics, the frequency of HPV vaccination recommendations, HPV knowledge and related attitudes were collected through the questionnaires., Results: Among 1,371 participants, only 30.2% reported that they frequently recommended HPV vaccination. Multivariate analyses indicated that female sex, being employed in obstetrics or gynecology departments and community health service centers, and having higher self-reported and actual knowledge of HPV were factors associated with a higher recommendation frequency. Factors including a self-perceived non-obligation to provide recommendations and difficulties in discussing sexual topics were significantly correlated with less frequent recommendations. Employment in a community health service center (OR = 2.068, 95% CI: 1.070-3.999) was the strongest factor associated with the frequency of HCPs' recommendations for HPV vaccination., Discussion: The frequency of HCPs' recommendations for HPV vaccination in China was much lower than that in many developed countries. To enhance the recommendation frequency, medical institutions should help HCPs gain more knowledge of HPV and master communication skills. At the same time, the government should take measures to enhance the accessibility of HPV vaccines. The media should help to alleviate people's concerns and encourage them to face up sexual health., 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 Mao, Zhao, Zhang, Li, Abdullah, Zheng and Wang.)

The aim of the present study was to examine the function of transgelin (TAGLN) and its underlying mechanism in the ferroptosis of esophageal squamous cell carcinoma (ESCC) cells. To meet this aim, the association between TAGLN expression and the prognosis of patients with ESCC was determined using tissue samples and clinical data. Gene Expression Omnibus databank and Gene Set Enrichment Analysis data were used to examine which genes were co‑expressed with TAGLN, as well as the influence of TAGLN on ESCC. Subsequently, Transwell chamber, wound healing, Cell Counting Kit‑8 viability and colony formation assays were performed to observe the effects of TAGLN on the migration, invasion, viability and proliferation of Eca‑109 and KYSE‑150 cells. The interaction between TAGLN and p53 in the regulation of ferroptosis was detected using reverse transcription‑quantitative PCR, co‑immunoprecipitation and fluorescence co‑localization assays, and a xenograft tumor model was established to examine the effect of TAGLN on tumor growth. The level of TAGLN expression in patients with ESCC was found to be low, compared with normal esophageal tissue, and a positive association was identified between the prognosis of ESCC and TAGLN expression. The expression of the ferroptosis marker protein, glutathione peroxidase 4, was found to be high, whereas that of acyl‑CoA synthetase long‑chain family member 4 was lower in patients with ESCC compared with expression levels in healthy patients. The overexpression of TAGLN resulted in a significant decrease in the invasive and proliferative capabilities of Eca‑109 and KYSE‑150 cells in vitro compared with the control group; in vivo , TAGLN overexpression was found to significantly decrease tumor size, volume and weight after one month of growth. In addition, the proliferation, migration and invasion of Eca‑109 cells in vivo was stimulated by the knockdown of TAGLN. The results of the transcriptome analysis further demonstrated that TAGLN was able to induce ferroptosis‑associated cell functions and pathways. Finally, TAGLN overexpression was found to promote ferroptosis in ESCC through its interaction with p53. Taken together, the findings of the present study suggested that the malignant development of ESCC may be inhibited by TAGLN through the manifestation of ferroptosis.

Objective: The aim of the article is to introduce a novel laser-based frameless stereotactic device that can locate intracranial lesions quickly and with computed tomograph (CT)/magnetic resonance imaging (MRI) films. Preliminary experiences of application in 416 cases are also summarized., Methods: From August in 2020 to October in 2022, a total of 416 cases of new minimalist laser stereotactic surgery have been performed on 415 patients. Of the 415 patients, 377 had intracranial hematomas, while the remaining cases were brain tumors or brain abscesses. Postoperative CT was used to evaluate the accuracy of catheterization of 405 patients according to the MISTIE study. The duration time of locating was recorded. Rebleeding refers to the definition: Compared with preoperative CT, the relative volume of postoperative hematoma increases by >33% or absolute volume increase >12.5 mL., Results: According to postoperative CT, the accuracy of 405 stereotactic catheterization cases was good in 346 cases (85.4%) and suboptimal in 59 cases (14.6%), with no poor results. Postoperative rebleeding occurred in 4 spontaneous cerebral hemorrhage cases and 1 brain biopsy case. The average localization time of supratentorial lesions was 13.2 minutes in the supine position, 21.5 minutes in the lateral position, and 27.6 minutes in the prone position., Conclusions: The new laser-based frameless stereotactic device is simple in principle and convenient in positioning operation of brain hematoma and abscess puncture, brain biopsy and tumor surgery, and appropriate to the precision requirements in most craniocerebral surgery., (Copyright © 2023 Elsevier Inc. All rights reserved.)