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Objective: There are various detrimental effects of excessive added sugar consumption on health, but the association of added sugars with frailty remains elusive. We aimed to examine the association between added sugar intake and frailty among American adults in the present cross-sectional study., Methods: This cross-sectional study is based on the National Health and Nutrition Examination Survey (NHANES) database. Data from NHANES spanning from 2007 to 2018 on frailty, added sugars, and covariates were collected. Added sugars were categorized into quartiles according to the recommended percentages by institutions. Weighted multivariable logistic regression was used to analyze the relationship between frailty and added sugars. Subgroup analysis was conducted based on sex, age, body mass index (BMI), smoking, alcohol consumption, hypertension, and diabetes status., Results: This study included 16,381 participants, with 13,352 (81.51%) in the non-frailty group and 3,029 (18.49%) in the frailty group. We found that added sugars were positively associated with frailty, and subgroup analysis showed that participants who were male, over the age of 60, had a low BMI, had previously smoked and consumed alcohol, had no hypertension, or had diabetes mellitus (DM) were more likely to be frail. Added sugar intake was positively associated with frailty. Subgroup analysis showed that the association was strongest in males, those aged >60, those with a low BMI, former smokers, former alcohol consumers, and people with no hypertension or DM. When added sugars are classified by energy percentage, populations with more than 25% of their energy coming from added sugars have similar results, with a higher prevalence of frailty., Conclusion: Added sugars are positively associated with a higher risk of frailty, and the association is stable among different populations., 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 Ji, Qiu, Tao, Xu, Pei, Wu, Huang and Qian.)

Objective: To explore the potential pathogenic genes of intestinal metaplasia., Methods: Twenty-one patients with intestinal metaplasia admitted to the Department of Gastroenterology at the Second Affiliated Hospital of Anhui University of Chinese Medicine from January, 2022 to June, 2022, and 21 healthy subjects undergoing gastroscopic examination during the same period were enrolled in this study. All the participants underwent gastroscopy and pathological examination, and gastric tissue samples were collected for transcriptome sequencing to screen for differentially expressed genes (DEGs). The biological functions of the DEGs were analyzed using bioinformatics analysis, and qRT-PCR was used to validate the results., Results: Transcriptomic sequencing identified a total of 1373 DEGs, including 827 upregulated and 546 downregulated ones. The top 6 upregulated genes ( AGMAT , CCL25 , FABP1 , CDX1 , SPINK4 , and MUC2 ), ranked based on their significance and average expression level, were selected for validation, and qRT-PCR showed significant upregulation of their mRNAs in the gastric tissues of patients with intestinal metaplasia ( P < 0.05)., Conclusion: AGMAT , CCL25 , FABP1 , CDX1 , SPINK4 , and MUC2 participate in the occurrence and development of intestinal metaplasia, and may serve as potential biomarkers for diagnosing intestinal metaplasia.

The incidence of chronic atrophic gastritis (CAG) is on the rise due to the growing pressure in modern social life, increasing bad living habits and emotional disorders (such as anxiety and depression), and the aging of the population. Of note, digestive system diseases are the dominant diseases in the field of traditional Chinese medicine (TCM). Therefore, this study evaluated the efficacy and safety of Piwei Peiyuan Prescription, a TCM prescription, in the treatment of CAG through a multicenter, double-blind, randomized, controlled design. This research was organized by the Second Affiliated Hospital of Anhui University of TCM and simultaneously performed in 6 centers. A total of 120 CAG patients were included and randomized into 2 groups: group A (treatment with Piwei Peiyuan granules plus Weifuchun Simulant) and Group B (treatment with Weifuchun Tablets plus Piwei Peiyuan Simulant). These 2 groups were compared in terms of gastroscopy scores, TCM syndrome scores, and serological indicators at baseline and within 12 weeks after treatment. According to endoscopic biopsy for pathological observation, atrophy (2.56 ± 1.08 vs 3.00 ± 1.00, P = .028) and intestinal epithelial hyperplasia (1.00 ± 1.43 vs 1.69 ± 1.80, P = .043) scores were lower in group A than in group B. For the more, group A had higher effective rates for inflammation, atrophy, and intestinal metaplasia (IM) in various regions of the stomach, especially for atrophy/IM of the gastric angle (64%, P = .034) and atrophy/IM of the lesser curvature of gastric antrum (63%, P = .042) than group B. According to TCM syndrome scores, Piwei Peiyuan Prescription improved the scores of gastric distension (2.30 ± 1.13 vs 2.80 ± 0.99, P = .022), preference for warmth and pressure (1.44 ± 1.06 vs 1.36 ± 1.10, P = .041), and poor appetite and indigestion (0.78 ± 0.66 vs 1.32 ± 0.72, P = .018). GAS, MTL, and PGE2 expression was significantly elevated after treatment with Piwei Peiyuan Prescription (P < .001). Piwei Peiyuan Prescription is effective for CAG treatment with high safety., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Esophageal cancer (EC) is a prevalent malignancy characterized by a low 5-year survival rate, primarily attributed to delayed diagnosis and limited therapeutic options. Currently, early detection of EC heavily relies on endoscopy and pathological examination, which pose challenges due to their invasiveness and high costs, leading to low patient compliance. The detection of DNA methylation offers a non-endoscopic, cost-effective, and secure approach that holds promising prospects for early EC detection., Methods: To identify improved methylation markers for early EC detection, we conducted a comprehensive review of relevant literature, summarized the performance of DNA methylation markers based on different input samples and analytical methods in EC early detection and screening., Findings: This review reveals that blood cell free DNA methylation-based method is an effective non-invasive method for early detection of EC, although there is still a need to improve its sensitivity and specificity. Another highly sensitive and specific non-endoscopic approach for early detection of EC is the esophageal exfoliated cells based-DNA methylation analysis. However, while there are substantial studies in esophageal adenocarcinoma, further more validation is required in esophageal squamous cell carcinoma., Conclusion: In conclusion, DNA methylation detection holds significant potential as an early detection and screening technology for EC., Competing Interests: All 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 Xu, Wang, Pei, Wang, Xue and Zhao.)

Zirconium carbide (ZrC) ceramics have a high melting point, low neutron absorption cross section, and excellent resistance to the impact of fission products and are considered to be one of the best candidate materials for fourth-generation nuclear energy systems. ZrC ceramics with a high relative density of 99.1% were successfully prepared via pressureless sintering using a small amount of MoSi 2 as an additive. The influence of the MoSi 2 content on the densification behavior, microstructure, mechanical properties, and thermal properties of ZrC ceramics was systematically investigated. The results show that the densification of ZrC was significantly enhanced by the introduction of MoSi 2 due to the formation of a liquid phase during sintering. In addition, the ZrC grains were refined due to the pinning effect of the generated silicon carbide. The flexural strength and Vickers hardness of ZrC ceramics with 2.5 vol% MoSi 2 sintered at 1850 °C were 408 ± 12 MPa and 17.1 GPa, respectively, which were approximately 30% and 10% higher compared to the samples without the addition of MoSi 2 . The improved mechanical properties were mainly attributed to the high relative density (99.1%) and refined microstructure.

Accumulating evidences have indicated that lipid-lowering drugs have effect for the treatment of cancers. However, causal associations between lipid-lowering drugs and the risk of cancers are still unclear. In our study, we utilized single nucleotide polymorphisms of proprotein convertase subtilis kexin 9 (PCSK9) inhibitors and 3-hydroxy-3-methylglutaryl-assisted enzyme A reductase (HMGCR) inhibitors and performed a drug target Mendelian randomization to explore the causal association between lipid-lowering drugs and the risk of cancers. Five regression methods were carried out, including inverse variance weighted (IVW) method, MR Egger, weighted median, simple mode and weighted mode methods, of which IVW method was considered as the main analysis. Our outcome dataset contained the risk of breast cancer (BC), colorectal cancer, endometrial cancer, gastric cancer (GC), hepatocellular carcinoma (HCC), lung cancer, esophageal cancer, prostate cancer (PC), and skin cancer (SC). Our results demonstrated that PCSK9 inhibitors were significant associated with a decreased effect of GC [IVW: OR = 0.482, 95% CI: 0.264-0.879, P = .017]. Besides, genetic inhibitions of HMGCR were significant correlated with an increased effect of BC [IVW: OR = 1.421, 95% CI: 1.056-1.911, P = .020], PC [IVW: OR = 1.617, 95% CI: 1.234-2.120, P = .0005] and SC [IVW: OR = 1.266, 95% CI: 1.022-1.569, P = .031]. For GC [IVW: OR = 0.559, 95% CI: 0.382-0.820, P = .0029] and HCC [IVW: OR = 0.241, 95% CI: 0.085-0.686, P = .0077], HMGCR inhibitors had a protective risk. Our method suggested that PCSK9 inhibitors were significant associated with a protective effect of GC. Genetic inhibitions of HMGCR were significant correlated with an increased effect of BC, PC and SC. Meanwhile, HMGCR inhibitors had a protective risk of GC and HCC. Subsequent studies still needed to assess potential effects between lipid-lowering drugs and the risk of cancers with clinical trials., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: To analyse the causal associations of different physical measures with osteoarthritis knee (KOA)., Methods: Exposure factors (weight, body mass index (BMI), body fat percentage, waist circumference, hip circumference, waist-hip ratio (WHR), and basal metabolic rate (BMR)), and outcome factor KOA were analyzed by inverse-variance weighted (IVW) method, along with heterogeneity test, sensitivity and pleiotropy analyses. Meta-analysis was used to combine the effect values of IVW methods in different data sources., Results: Weight, BMI, body fat percentage, waist circumference, hip circumference and BMR analyses showed causal association with increased KOA risk, while WHR analysis indicated a reduction of the incidence of KOA. P-value for all the results was less than 0.05 and F-value large than 20. All results were negative for heterogeneity tests and sensitivity analyses, and there was pleiotropy in weight and BMR. Meta-analysis results showed that the results of Odds Ratios (95% Confidence Intervals) for Weight (1.43(1.35-1.51)), BMI (1.40(1.10-1.78)), body fat percentage (1.56(1.44-1.68)), waist circumference (1.40(1.10-1.78)), hip circumference (1.37(1.30-1.44)), WHR (0.86(0.71-1.04)) and BMR (1.36(1.27-1.46) were consistent with the ones by Mendelian randomization analyses., Conclusions: Body fat percentage may be a better indicator of KOA than BMI. In addition, weight and BMR may have a causal effect in KOA, but WHR does not have a causal relationship. BMI, body fat percentage, waist circumference, and hip circumference has a causal effect on KOA., (© 2024. The Author(s).)

Growing evidences of recent studies have shown that gut microbrome are causally related to digestive system diseases (DSDs). However, causal relationships between the gut microbiota and the risk of DSDs still remain unclear. We utilized identified gut microbiota based on class, family, genus, order and phylum information and digestive system diseases genome-wide association study (GWAS) dataset for two-sample Mendelian randomization (MR) analysis. The inverse variance weighted (IVW) method was used to evaluate causal relationships between gut microbiota and 7 DSDs, including chronic gastritis, colorectal cancer, Crohn's disease, gastric cancer, gastric ulcer, irritable bowel syndrome and esophageal cancer. Finally, we verified the robustness of MR results based on heterogeneity and pleiotropy analysis. We discovered 15 causal associations with genetic liabilities in the gut microbiota and DSDs, such as genus Victivallis, genus RuminococcaceaeUCG005, genus Ruminococcusgauvreauiigroup, genus Oxalobacter and so on. Our MR analysis revealed that the gut microbiota is causally associated with DSDs. Further researches of the gut microbiota and the pathogenesis of DSDs are still significant and provide new methods for the prevention and treatment of DSDs., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Visceral pain induced by pancreatic cancer seriously affects patients' quality of life, and there is no effective treatment, because the mechanism of its neural circuit is unknown. Therefore, the aim of this study is to explore the main neural circuit mechanism regulating visceral pain induced by pancreatic cancer in mice., Methods: The mouse model of pancreatic cancer visceral pain was established on C57BL/6N mice by pancreatic injection of mPAKPC-luc cells. Abdominal mechanical hyperalgesia and hunch score were performed to assess visceral pain; the pseudorabies virus (PRV) was used to identify the brain regions innervating the pancreas; the c-fos co-labeling method was used to ascertain the types of activated neurons; in vitro electrophysiological patch-clamp technique was used to record the electrophysiological activity of specific neurons; the calcium imaging technique was used to determine the calcium activity of specific neurons; specific neuron destruction and chemogenetics methods were used to explore whether specific neurons were involved in visceral pain induced by pancreatic cancer., Results: The PRV injected into the pancreas was detected in the paraventricular nucleus of the hypothalamus (PVN). Immunofluorescence staining showed that the majority of c-fos were co-labeled with glutamatergic neurons in the PVN. In vitro electrophysiological results showed that the firing frequency of glutamatergic neurons in the PVN was increased. The calcium imaging results showed that the calcium activity of glutamatergic neurons in the PVN was enhanced. Both specific destruction of glutamatergic neurons and chemogenetics inhibition of glutamatergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer., Conclusions: Glutamatergic neurons in the PVN participate in the regulation of visceral pain induced by pancreatic cancer in mice, providing new insights for the discovery of effective targets for the treatment of pancreatic cancer visceral pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-23-442/coif). The authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

The advent of tumor immunotherapy in patients has revolutionized the treatment of tumors and significantly improved survival rates for a wide range of tumors. However, the full therapeutic potential of immune checkpoint inhibitors (ICIs) has yet to be realized, as not all patients have a lasting survival benefit from them, and a significant proportion of patients show primary or acquired resistance to immunotherapy. Bifidobacterium is one of the most common probiotics, and its antitumor and immunomodulatory effects have been demonstrated in recent years, but its immunomodulatory effects in tumors, especially on ICIs and in combination, have not been extensively studied in clinical practice, and its effects on the immune system and the mechanisms that modulate immunotherapy are largely unknown. Therefore, this review will focus on the immunomodulatory effects of Bifidobacteria in malignancies and the possible mechanisms of action of Bifidobacteria on immunotherapy in the hope of providing a basis for further research and better application of Bifidobacteria in clinical practice., (© 2024. The Author(s).)

The effects of Ti doping on the microstructure and properties of SiC p /Al composites fabricated by pressureless infiltration were comprehensively investigated using first-principles calculations and experimental analyses. First-principles calculations revealed that the interface wetting and bonding strength in an Al/SiC system could be significantly enhanced by Ti doping. Subsequently, the Ti element was incorporated into SiC preforms in the form of TiO 2 and TiC to verify the influence of Ti doping on the pressureless infiltration performance of SiC p /Al composites. The experimental results demonstrated that the pressureless infiltration of molten Al into SiC preforms was promoted by adding TiC or TiO 2 due to the improved wettability. However, incorporating TiO 2 leads to the growth of AlN whiskers under a N 2 atmosphere, thereby hindering the complete densification of the composites. On the other hand, TiC doping can improve wettability and interface strength without deleterious reactions. As a consequence, the TiC-doped SiC p /Al composites exhibited excellent properties, including a high relative density of 99.4%, a bending strength of 287 ± 18 MPa, and a thermal conductivity of 142 W·m -1 ·K -1 .

Liquefied petroleum gas (LPG) is widely used for its cleanliness and high efficiency in industry and city life. In order to improve the suppression effect on LPG explosion, a constant volume combustion bomb was used to investigate the synergistic influence of N 2 /ultrafine water mist on the explosion and combustion characteristics of 6% premixed LPG/air gas. The results showed that (1) the effect of a single ultrafine water mist on suppressing LPG explosion is unstable. When the concentration of ultrafine water mist is low, the flame acceleration in the initial stage of explosion is promoted, and when the ultrafine water mist with a mass fraction of 420 g/m 3 is introduced, the maximum pressure rise rate increases. (2) The combination of N 2 /ultrafine water mist has a synergistic effect on LPG explosion. Compared to the individual suppression effects, the combination of N 2 /ultrafine water mist showed more effective suppression on the explosion pressure, flame propagation, and flame instability of LPG explosion. (3) Through the mechanism analysis, it is found that the combined action of N 2 / ultrafine water mist can better reduce the mole fraction and ROP peak of active free radicals such as H, O, and OH by inhibiting the main reaction of generating H, O, and OH radicals during the explosion of LPG, resulting in the reduction of flame free radicals in the explosion system, thus effectively inhibiting the chain reaction of ignition and explosion of LPG. This research can provide guidance for a better understanding and implementation of gas-liquid two-phase suppression technology for LPG explosion., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

MicroRNAs (miRNAs) are increasingly recognized as promising biomarkers for early disease diagnosis and prognosis. Therefore, the need for rapid, robust methods for multiplex miRNA detection in biological research and clinical diagnosis is crucial. This study introduces a novel multiplex miRNA detection method, SMOS-qPCR (Sensitive and Multiplexed One-Step RT-qPCR). The method integrates multiplexed reverse transcription and TaqMan-based qPCR into a single tube, employing a one-step operation on a real-time PCR system. We investigated the effect of 3' end phosphorylation of the Linker, Linker concentration and probe concentration on the SMOS-qPCR, resulted in a wide linear range from 1 fM to 0.1 zM (R 2  ≥ 0.99 for each miRNA), surpassing the capabilities of stem-loop RT-qPCR and SYBR Green One-step RT-qPCR. The method showed excellent performance in distinguishing mature miRNA from miRNA precursor, and successfully detected four miRNAs in a single tube without cross-interference. Its high specificity enables precise differentiation of less than 1% nonspecific signal. Finally, we demonstrated the effectiveness of the SMOS-qPCR system in detecting circulating miRNAs in serum samples, distinguishing between esophageal cancers and health individuals with high AUC values (>0.940). In conclusion, the proposed SMOS-qPCR system offers a straightforward and promising approach for miRNA profiling in future clinical applications., Competing Interests: Declaration of competing interest Authors Guodong Zhao, Kai Wang and Xiaoyu Liu are employed by Suzhou VersaBio Technologies Co. Ltd. The remaining 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 Elsevier B.V. All rights reserved.)

Traditional growing rod (TGR) provides a corrective moment for deformed segments to straighten the spine, whose clinical efficacy has proven positive and growth-friendly. However, an insufficient understanding of orthopedic mechanisms can affect the development of clinical strategies. This research attempts to analyze the spine that has undergone four distraction operations: exploring the spinal orthopedic mechanism, including alignment, growth, and morphology. In this study, the spinal morphology curves were illustrated in three human planes to exhibit the changes in spinal alignment. The spinal growth characteristics were measured to discuss the unsynchronized and diminishing growth rate. The spinal deformations were evaluated to indicate asymmetric growth. As a result, the spinal alignment changes indicated the orthopedic process improved, but the re-unbalance occurred after multiple distractions. Then, unsynchronized growth existed in the superior and inferior segments, and the growth rate over every distraction diminished. Finally, asymmetric growth was indicated as the axial/circumferential growth ratio getting greater and the cuneate level approaching normal. Accordingly, a TGR is growth-friendly, but combining the osteotomy fusion of lumbar segments for severe early-onset scoliosis may be an excellent choice to solve the insufficient corrective stimulation. Regarding the distraction process, reshaping before the final fusion can fix the balance loss, and a prolonged distraction frequency fits the law of diminishing return. In conclusion, studying orthopedic mechanisms based on morphological measurement can guide clinical strategy optimization., (© 2023 Orthopaedic Research Society.)

Background: Given the pivotal role of neuroinflammation in chronic pain and that the paraventricular nucleus of the hypothalamus (PVN) is a crucial brain region involved in visceral pain regulation, we sought to investigate whether the targeted modulation of microglia and astrocytes in the PVN could ameliorate pancreatic cancer-induced visceral pain (PCVP) in mice., Methods: Using a mouse model of PCVP, achieved by tumor cell injection at the head of the pancreas, we measure the number of glial cells, and at the same time we employed minocycline to inhibit microglia and chemogenetic methods to suppress astrocytes in order to investigate the respective roles of microglia and astrocytes within the PVN in PCVP., Results: Mice exhibited visceral pain at 12, 15 and 18 days post-tumor cell injection. We observed a significant increase in the population of both microglia and astrocytes. Inhibition of microglial activity through minocycline microinjection into the PVN resulted in alleviation of visceral pain within 30 and 60 min. Similarly, chemogenetic inhibition of astrocyte function at 14 and 21 days post-injection also led to relief from visceral pain., Conclusions: This study found that PVN microglia and astrocytes were involved in regulating PCVP. Our results suggest that targeting glia may be a potential approach for alleviating visceral pain in patients with pancreatic cancer., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-42/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

Background: For patients with pancreatic cancer, visceral pain is a debilitating symptom that significantly compromises their quality of life. Unfortunately, the lack of effective treatment options can be attributed to our limited understanding of the neural circuitry underlying this phenomenon. The primary objective of this study is to elucidate the fundamental mechanisms governing visceral pain induced by pancreatic cancer in murine models., Methods: A mouse model of pancreatic cancer visceral pain was established in C57BL/6N mice through the intrapancreatic injection of mPA KPC -luc cells. Abdominal mechanical hyperalgesia and hunch score were employed to evaluate visceral pain, whereas the in vitro electrophysiological patch-clamp technique was utilized to record the electrophysiological activity of GABAergic neurons. Specific neuron ablation and chemogenetics methods were employed to investigate the involvement of GABAergic neurons in pancreatic cancer-induced visceral pain., Results: In vitro electrophysiological results showed that the firing frequency of GABAergic neurons in the paraventricular nucleus of the hypothalamus (PVN) was decreased. Specific destruction of GABAergic neurons in the PVN exacerbated visceral pain induced by pancreatic cancer. Chemogenetics activation of GABAergic neurons in the PVN alleviated visceral pain induced by pancreatic cancer., Conclusions: GABAergic neurons located in PVN play a crucial role in precipitating visceral pain induced by pancreatic cancer in mice, thereby offering novel insights for identifying effective targets to treat pancreatic cancer-related visceral pain., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://jgo.amegroups.com/article/view/10.21037/jgo-24-50/coif). The authors have no conflicts of interest to declare., (2024 Journal of Gastrointestinal Oncology. All rights reserved.)

To explore the association between lipid markers and osteoarthritis (OA). First, the National Health and Nutrition Examination Survey (NHANES) database was used to screen participants with lipid markers, OA and relevant covariates, and logistic regression was used to analyze the association between lipid markers and OA; Then, under the theoretical framework of Mendelian randomization (MR), two-sample MR was performed using GWAS data of lipid markers and OA to explore the causal association between the two, which was analyzed by inverse variance weighting (IVW) method. Heterogeneity test, sensitivity analysis and pleiotropy analysis were also performed. The NHANES database screened a total of 3706 participants, of whom 836 had OA and 2870 did not have OA. When lipid markers were used as continuous variables, multivariate logistic results showed an association between HDL, LDL and OA (HDL, OR (95%):1.01 (1.00, 1.01); LDL, OR (95%):1.00 (0.99, 1.00)). When lipid markers were used as categorical variables, multivariate logistic results showed the fourth quartile result of 0.713 (0.513, 0.992) for LDL relative to the first quartile. In MR study, the results of the IVW method for TG, TL, HDL and LDL showed OR (95% CI) of 1.06 (0.97-1.16), 0.95 (0.85-1.06), 0.94 (0.86-1.02) and 0.89 (0.80-0.998) with P-values of 0.21, 0.37. 013, 0.046. The heterogeneity tests and multiplicity analyses showed P-values greater than 0.05, and sensitivity analyses showed no abnormal single nucleotide polymorphisms. Through NHANES database and MR analyses, LDL was found to be a protective factor for OA, while HDL still needs further study. Our results provide new biomarkers for preventive and therapeutic strategies for OA., (© 2024. The Author(s).)

Background: Low back pain is highly prevalent and the main cause of years lived with disability, but data on the burden and trends of low back pain (LBP) in adolescents and young adults (AYAs) are sparse., Objective: To assess trends in the burden of LBP among AYAs aged 15-39 years at the global, regional and national levels from 1990 to 2019., Methods: Data from the Global Burden of Disease (GBD) 2019 were used to analyze incidence, prevalence and Disability-adjusted life year (DALY) due to LBP at global, regional, and national levels. Joinpoint regression analysis calculated the average annual percentage changes (AAPC). Then analyse the association between incidence, prevalence and DALYs and socioeconomic development using the GBD Socio-demographic Index (SDI). Finally, projections were made until 2030 and calculated in Nordpred., Results: The incidence, prevalence and DALYs rates (95%UI) were 2252.78 (1809.47-2784.79), 5473.43 (4488.62-6528.15) and 627.66 (419.71-866.97) in 2019, respectively. From 1990 to 2019, the incidence, prevalence, and DALYs rates AAPC (95%CI) were -0.49 (-0.56 to -0.42), -0.58 (-0.65 to -0.51) and -0.57 (-0.64 to -0.5), respectively. Incidence, prevalence, and DALYs rates in South Asia, East Asia, High-income North America, Western Europe, and Australasia decreased with SDI. Incidence, prevalence, and DALYs rates in Central Asia, Central Europe, and Eastern Europe decreased and then increased with SDI. At the national level, the incidence, prevalence, and DALYs rates are high in the United States and low in India and China. From the 2020 to 2030, most regions is predicted to decline., Conclusion: LBP in AYAs is a major global public problem with a high burden. There are large differences in incidence, prevalence and DALYs across SDIs, regions and countries. there is still a need to focus on LBP in AYAs and tailor interventions to reduce the future burden of this condition.

Background : Immunotherapy plays a significant role in the treatment of hepatocellular carcinoma (HCC). Members of the S100 protein family (S100s) have been widely implicated in the pathogenesis and progression of tumors. However, the exact mechanism by which S100s contribute to tumor immunity remains unclear. Methods: To explore the role of S100s in HCC immune cells, we collected and comparatively analyzed single-cell RNA sequencing (scRNA-seq) data of HCC and hepatitis B virus-associated HCC. By mapping cell classification and searching for S100s binding targets and downstream targets. Results: S100A6/S100A11 was differentially expressed in tumor T cells and involved in the nuclear factor (NF) κB pathway. Further investigation of the TCGA dataset revealed that patients with low S100A6/S100A11 expression had a better prognosis. Temporal cell trajectory analysis showed that the activation of the NF-κB pathway is at a critical stage and has an important impact on the tumor microenvironment. Conclusion: Our study revealed that S100A6/S100A11 could be involved in regulating the differentiation and cellular activity of T-cell subpopulations in HCC, and its low expression was positively correlated with prognosis. It may provide a new direction for immunotherapy of HCC and a theoretical basis for future clinical applications., Competing Interests: Declaration of Conflicting InterestThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: Selecting the optimal tracheal tube size is critically important for pediatric patients. Age-based formulas are often used, but still have limitations. The aim of this prospective study was to investigate whether middle finger measurements correlate with cuffed tracheal tube size and to further develop a prediction model based on these measurements., Methods: Patients under 12 years of age scheduled for elective surgery involving tracheal intubation were enrolled in the study. The length was determined from the tip of the distal metacarpal to the palm's root on the palm side, while the circumference was measured at the base of the palm using a soft tape measure. The appropriate cuffed tracheal tube size was determined based on specific criteria. If the tube encountered resistance during insertion or required an airway pressure >25 cmH 2 O to detect an audible leak, it was replaced with a tube 0.5 mm smaller. Conversely, if an audible leak occurred at an airway pressure <10 cmH 2 O, or peak pressure >25 cmH 2 O, or the cuff pressure >25 cmH 2 O to achieve a seal, the tube was exchanged for one with a 0.5 mm larger. Linear regression analysis was used to examine the association between middle finger circumference and length with the cuffed tracheal tube size. Subsequently, regression equations were constructed based on the results of the linear regression analysis and their predictive performance was compared to the conventional age-based formulas, including the Khine formula and Motoyama formula. The predictive performance was evaluated by mean absolute error (MAE), root mean square error (RMSE), and prediction accuracy., Results: A total of 261 patients were analyzed in our study. The mean age of the patients was 46.19±35.83 months. The linear relationship was observed between the cuffed tracheal tube size and the middle finger circumference and middle finger length with R 2 values of 0.77 and 0.73, respectively. In comparison to conventional age-based formulas, both middle finger circumference and middle finger length demonstrated superior predictive performance, characterized by lower MAE and RMSE, as well as higher prediction accuracy. Notably, the regression equation based on the middle finger circumference obtained the higher predictive accuracy of 0.590, with an MAE of 0.259 and an RMSE of 0.333 as opposed to the predictive accuracy of 0.391, MAE of 0.349, and RMSE of 0.473 derived from conventional age-based formulas. Based on the regression coefficients of linear regression, simplified formulas were proposed, with the middle finger circumference-based formula emerging as the most accurate and simple option., Conclusions: The appropriate cuffed tracheal tube size could be predicted by the middle finger circumference. Our proposed formula 'cuffed tracheal tube internal diameter (mm) = middle finger circumference (cm) - 0.2' has the potential to improve the selection of the cuffed tracheal tube size in pediatric patients., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tp.amegroups.com/article/view/10.21037/tp-23-502/coif). T.E. received grants or contracts from National Institutes of Health (NIH). The other authors have no conflicts of interest to declare., (2023 Translational Pediatrics. All rights reserved.)

Lung cancer is one of the most server mortality in the world and remains a huge threat to human health. Recently, cisplatin-based chemotherapy represented a common therapeutic strategy, however, cisplatin resistance greatly limits the therapy efficacy. We investigated whether KIAA0101 plays a role in cisplatin resistance of lung cancer cells and its mechanisms of action. The expression of KIAA0101 was evaluated based on comprehensive bioinformatic analysis. KIAA0101 knockdown and overexpression A549 cells were constructed to investigate its effects on cell proliferation and apoptosis induced by cisplatin treatment. Western blot analysis was performed to measure the levels of p53-related apoptosis proteins. We found that KIAA0101 was greatly increased in lung cancer tissues and cells. Knockdown of KIAA0101 suppressed cell proliferation and increased cisplatin-induced apoptosis. Knockdown of KIAA0101 also augmented the cisplatin-induced cell apoptosis signaling pathway. Then p53 was found to account for the role of KIAA0101 in cisplatin resistance. In conclusion, our findings provide a novel factor of KIAA0101 in lung cancer resistance, which suggests as a novel target for lung cancer therapy.

Background: Lung adenocarcinoma (LUAD) is a common cancer with a poor prognosis. Pyroptosis is an important process in the development and progression of LUAD. We analyzed the risk factors affecting the prognosis of patients and constructed a nomogram to predict the overall survival of patients based on different pyroptosis-related genes (PRGs) subtypes., Methods: The genomic data of LUAD were downloaded from the TCGA and GEO databases, and all data were filtered and divided into TCGA and GEO cohorts. The process of data analysis and visualization was performed via R software. The data were classified based on different PRGs subtypes using the K-means clustering method. Then, the differentially expressed genes were identified between two different subtypes, and risk factors analysis, survival analysis, functional enrichment analysis, and immune cells infiltration landscape analysis were conducted. The COX regression analysis was used to construct the prediction model., Results: Based on the PRGs of LUAD, the patients were divided into two subtypes. We found the survival probability of patients in subtype 1 is higher than that in subtype 2. The results of the logistics analysis showed that gene risk score was closely associated with the prognosis of LUAD patients. The results of GO analysis and KEGG analysis revealed important biological processes and signaling pathways involved in the differentially expressed proteins between the two subtypes. Then we constructed a prediction model of patients' prognosis based on 13 genes, including IL-1A, P2RX1, GSTM2, ESYT3, ZNF682, KCNF1, STK32A, HHIPL2, GDF10, NDC80, GSTA1, BCL2L10, and CCR2. This model was strongly related to the overall survival (OS) and also reflects the immune status in patients with LUAD., Conclusion: In our study, we examined LUAD heterogeneity with reference to pyroptosis and found different prognoses between the two subtypes. And a novel prediction model was constructed to predict the OS of LUAD patients based on different PRGs signatures. The model has shown excellent predictive efficiency through validation., (© 2023. The Author(s).)

Background: Although it is critical to understand the accelerated degeneration of adjacent segments after fusion, the biomechanical properties of the spine have not been thoroughly studied after various fusion techniques. This study investigates whether four Roussouly's sagittal alignment morphotypes have different biomechanical characteristics after different single- or double-level spinal fixations., Methods: The parametric finite element (FE) models of Roussouly's type (1-4) were developed based on the radiological data of 625 Chinese community population. The four Roussouly's type models were reassembled into four fusion models: single-level L4-5 Coflex fixation model, single-level L4-5 Fusion (pedicle screw fixation) model, double-level Coflex (L4-5) + Fusion (L5-S1) model, and double-level Fusion (L4-5) + Fusion (L4-5) model. A pure moment of 7.5 Nm was applied to simulate the physiological activities of flexion, extension, lateral bending and axial rotation., Results: Both single-level and double-level spinal fixation had the greatest effect on lumbar range of motion, disc pressure, and annulus fibrosis stress in flexion, followed by lateral bending, extension, and axial rotation. In all models, the upper adjacent segment was the most influenced by the implantation and bore the most compensation from the fixed segment. For Type 2 lumbar, the L4-L5 Coflex effectively reduced the disc pressure and annulus fibrosis stress in adjacent segments compared to the L4-L5 Fusion. Similarly, the L4-L5 Coflex offered considerable advantages in preserving the biomechanical properties of adjacent segments for Type 1 lumbar. For Type 4 lumbar, the L4-L5 Coflex did not have superiority over the L4-L5 Fusion, resulting in a greater increase in range of motion at adjacent segments in flexion and extension. The difference between the two fixations was not apparent in Type 3 lumbar. Compared to the single-level Fusion, the changes in motion and mechanics of the lumbar increased after both the double-level Coflex + Fusion and Fusion + Fusion fixations, while the differences between two double-level fixation methods on adjacent segments of the four lumbar models were similar to that of the single-level fixation., Conclusion: Type 3 and Type 4 lumbar have good compensatory ability and therefore allow for a wider range of surgical options, whereas surgical options for small lordotic Type 1 and Type 2 lumbar are more limited and severe., (© 2023. The Author(s).)

Microsporidia are a group of obligate intracellular parasites that infect almost all animals, causing serious human diseases and major economic losses to the farming industry. Nosema bombycis is a typical microsporidium that infects multiple lepidopteran insects via fecal-oral and transovarial transmission (TOT); however, the underlying TOT processes and mechanisms remain unknown. Here, we characterized the TOT process and identified key factors enabling N. bombycis to invade the ovariole and oocyte of silkworm Bombyx mori. We found that the parasites commenced with TOT at the early pupal stage when ovarioles penetrated the ovary wall and were exposed to the hemolymph. Subsequently, the parasites in hemolymph and hemolymph cells firstly infiltrated the ovariole sheath, from where they invaded the oocyte via two routes: (I) infecting follicular cells, thereby penetrating oocytes after proliferation, and (II) infecting nurse cells, thus entering oocytes following replication. In follicle and nurse cells, the parasites restructured and built large vacuoles to deliver themselves into the oocyte. In the whole process, the parasites were coated with B. mori vitellogenin (BmVg) on their surfaces. To investigate the BmVg effects on TOT, we suppressed its expression and found a dramatic decrease of pathogen load in both ovarioles and eggs, suggesting that BmVg plays a crucial role in the TOT. Thereby, we identified the BmVg domains and parasite spore wall proteins (SWPs) mediating the interaction, and demonstrated that the von Willebrand domain (VWD) interacted with SWP12, SWP26 and SWP30, and the unknown function domain (DUF1943) bound with the SWP30. When disrupting these interactions, we found significant reductions of the pathogen load in both ovarioles and eggs, suggesting that the interplays between BmVg and SWPs were vital for the TOT. In conclusion, our study has elucidated key aspects about the microsporidian TOT and revealed the key factors for understanding the molecular mechanisms underlying this transmission., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Target gastrointestinal cancers (GICs), encompassing esophageal cancer (EC), gastric cancer (GC), and colorectal cancer (CRC), originate within a single readily accessible luminal organ system and are diagnosable using endoscopy. However, endoscopy is an invasive procedure with low compliance and no plasma-based DNA methylation assay for the early detection of GICs., Methods: Nine potential DNA methylation markers were identified and evaluated in tissue (n=60) and plasma (n=155) cohorts to select the most suitable markers. A training cohort (n=244) and a validation cohort (n=199), including GICs patients, benign tumors, gastrointestinal polyps, and controls, were enrolled to develop and validate a DNA methylation panel. An independent prospective cohort (n=158) was used to validate the panel's performance and compare it with blood protein tumor markers., Results: Six out of nine candidate methylation markers with excellent discrimination abilities in both tissue and plasma cohorts were selected for the DNA methylation panel. The panel demonstrated high AUC values of 0.937 (EC), 0.968 (GC), and 0.987 (CRC) in training cohort, and achieved AUC values of 0.921 (EC), 0.921 (GC), and 0.959 (CRC) in validation cohort. Notably, it achieved impressive AUC values of 0.971 and 0.843 for identifying stage I GICs in the training and validation cohorts, respectively. In the prospective cohort, the six-marker panel showed comparable AUC values to CEA, AFP, and CA19-9 (0.935, 0.769, 0.663, and 0.668, respectively)., Conclusion: This study successfully developed and validated a novel, robust, sensitive, and specific plasma-based DNA methylation panel, offering a promising strategy for the early detection of GICs., Competing Interests: Declaration of Competing Interest Authors Guodong Zhao, Lishuang Song, Kai Wang and Shangmin Xiong are employed by Suzhou VersaBio Technologies Co. Ltd. The remaining 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Scanning probe lithography (SPL) is a promising technology to fabricate high-resolution, customized and cost-effective features at the nanoscale. However, the quality of nano-fabrication, particularly the critical dimension, is significantly influenced by various SPL fabrication techniques and their corresponding process parameters. Meanwhile, the identification and measurement of nano-fabrication features are very time-consuming and subjective. To tackle these challenges, we propose a novel framework for process parameter optimization and feature segmentation of SPL via machine learning (ML). Different from traditional SPL techniques that rely on manual labeling-based experimental methods, the proposed framework intelligently extracts reliable and global information for statistical analysis to fine-tune and optimize process parameters. Based on the proposed framework, we realized the processing of smaller critical dimensions through the optimization of process parameters, and performed direct-write nano-lithography on a large scale. Furthermore, data-driven feature extraction and analysis could potentially provide guidance for other characterization methods and fabrication quality optimization., Competing Interests: Conflict of interestY. L. and Z. Z. applied for two patents related to this work in China (nos. 202211125769.7 and 202310202321.9)., (© Aerospace Information Research Institute, Chinese Academy of Sciences 2023.)

Previous studies reported inconsistent results regarding the association between keratinocyte carcinoma (KC) and exogenous hormone therapy. This study aimed to investigate the association between the use of exogenous sex hormones and the risk of KC among women. The databases of PubMed, Ovid Medline, Cochrane, and Web of Science were searched until May 2023. A total of 5293 patients with KC and 106,424 controls were included for analysis. The meta-analysis indicated that oral contraceptives (OC) and hormonal replacement therapy (HRT) use were associated with an increased risk of squamous cell carcinoma (SCC) (OR/RR = 1.25, 95% CI 1.10 to 1.43, I 2  = 41.6%, p = 0.080). Subgroup analysis showed that OC use increased the risk of SCC (OR/RR = 1.37, 95% CI 1.15 to 1.63), whereas no significant association was shown between HRT use and risk of SCC (OR/RR = 1.13, 95% CI 0.93 to 1.37). Additionally, OC and HRT use were linked to an increased risk of basal cell carcinoma (BCC) (OR/RR = 1.16, 95% CI 1.09 to 1.25, I 2  = 30.1%, p = 0.188). Further subgroup analysis suggested both OC and HRT use were associated with an increased risk of BCC (OC: OR/RR = 1.13, 95% CI 1.01 to 1.25; HRT: OR/RR = 1.19, 95% CI 1.09 to 1.30). In conclusion, our findings support the hypothesis that the risk of KC among women may be affected by the use of exogenous hormones., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Esophageal cancer (EC) is a leading cause of cancer-related deaths in China, with the 5-year survival rate reaching less than 30%, because most cases were diagnosed and treated at the advanced stage. However, there is still a lack of low-cost, efficient, and accurate non-invasive methods for the early detection of EC at present. Methods: A total of 48 EC plasma and 101 control plasma samples were collected in a training cohort from 1 January 2021 to 31 December 2021, and seven cancer-related DNA methylation markers ( ELMO1 , ZNF582 , FAM19A4 , PAX1 , C13orf18 , JAM3 and TERT ) were tested in these samples to select potential markers. In total, 20 EC, 10 gastric cancer (GC), 10 colorectal cancer (CRC), and 20 control plasma samples were collected in a validation cohort to evaluate the two-gene panel. Results: ZNF582 , FAM19A4 , JAM3 , or TERT methylation in plasma was shown to significantly distinguish EC and control subjects ( p < 0.05), and the combination of ZNF582 and FAM19A4 methylation was the two-gene panel that exhibited the best performance for the detection of EC with 60.4% sensitivity (95% CI: 45.3%-73.9%) and 83.2% specificity (95% CI: 74.1%-89.6%) in the training cohort. The performance of this two-gene panel showed no significant difference between different age and gender groups. When the two-gene panel was combined with CEA, the sensitivity for EC detection was further improved to 71.1%. In the validation cohort, the sensitivity of the two-gene panel for detecting EC, GC, and CRC was 60.0%, 30.0%, and 30.0%, respectively, with a specificity of 90.0%. Conclusion: The identified methylation marker panel provided a potential non-invasive strategy for EC detection, but further validation should be performed in more clinical centers., Competing Interests: Authors GZ, YW, XW, and SX were employed by Suzhou VersaBio Technologies Co., Ltd. The remaining 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 Pei, Zhao, Geng, Wang, Wang, Wang, Xiong and Zheng.)

In recent years, bone tissue engineering (BTE) has played an essential role in the repair of bone tissue defects. Although bioactive factors as one component of BTE have great potential to effectively promote cell differentiation and bone regeneration, they are usually not used alone due to their short effective half-lives, high concentrations, etc. The release rate of bioactive factors could be controlled by loading them into scaffolds, and the scaffold microstructure has been shown to significantly influence release rates of bioactive factors. Therefore, this review attempted to investigate how the scaffold microstructure affected the release rate of bioactive factors, in which the variables included pore size, pore shape and porosity. The loading nature and the releasing mechanism of bioactive factors were also summarized. The main conclusions were achieved as follows: i) The pore shapes in the scaffold may have had no apparent effect on the release of bioactive factors but significantly affected mechanical properties of the scaffolds; ii) The pore size of about 400 μm in the scaffold may be more conducive to controlling the release of bioactive factors to promote bone formation; iii) The porosity of scaffolds may be positively correlated with the release rate, and the porosity of 70%-80% may be better to control the release rate. This review indicates that a slow-release system with proper scaffold microstructure control could be a tremendous inspiration for developing new treatment strategies for bone disease. It is anticipated to eventually be developed into clinical applications to tackle treatment-related issues effectively., 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 Pei, Hu, Wu, Lu, Zhang, Zhang and Wu.)

Esophageal, gastric, liver, and colorectal cancers represent four prevalent gastrointestinal cancers that pose substantial threats to global health due to their high morbidity and mortality rates. Peroxiredoxin 1 (PRDX1), a significant component of the PRDXs family, primarily functions to counteract the peroxides produced by metabolic activities in the body, thereby maintaining the dynamic equilibrium of peroxides in vivo . Intriguingly, PRDX1 expression correlates strongly with cancer's onset, progression, and prognosis. This study mainly applied bioinformatics methods to analyze PRDX1's expression, diagnosis, and prognosis in gastrointestinal cancers and to summarize current research advancements. Evidence from the bioinformatics database suggested that the high expression of PRDX1 was a prominent characteristic of these four gastrointestinal cancers, with this observation reaching statistical significance. The high expression of PRDX1 in gastrointestinal cancer cells also confirms this result. Notably, the primary alteration in PRDX1 within these cancers is the presence of genetic mutations. PRDX1 demonstrated the highest diagnostic efficacy for colorectal cancer. Nevertheless, elevated PRDX1 levels only significantly diminished the survival time of liver cancer patients, exerting no statistically significant impact on the survival duration of patients afflicted by the other three types of gastrointestinal cancers. Recent research has indicated variability in PRDX1 expression across different cancer types, with high expression being predominantly observed in these four gastrointestinal cancers and, in most instances, unfavorable prognosis. These findings broadly align with the results derived from bioinformatics. This research underscores the high expression of PRDX1 in gastrointestinal cancers, its relevance to the diagnosis and prognosis monitoring of these cancers, and its potential to guide clinical treatment for these cancers., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

Background: Inflammatory bowel disease (IBD) is a global disease with a growing public health concern and is associated with a complex interplay of factors, including the microbiota and immune system. Resveratrol, a natural anti-inflammatory and antioxidant agent, is known to relieve IBD but the mechanism involved is largely unexplored., Methods: This study examines the modulatory effect of resveratrol on intestinal immunity, microbiota, metabolites, and related functions and pathways in the BALB/c mice model of IBD. Mouse RAW264.7 macrophage cell line was used to further explore the involvement of the macrophage-arginine metabolism axis. The treatment outcome was assessed through qRT-PCR, western blot, immunofluorescence, immunohistochemistry, and fecal 16S rDNA sequencing and UHPLC/Q-TOF-MS., Results: Results showed that resveratrol treatment significantly reduced disease activity index (DAI), retained mice weight, repaired colon and spleen tissues, upregulated IL-10 and the tight junction proteins Occludin and Claudin 1, and decreased pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. Resveratrol reduced the number of dysregulated metabolites and improved the gut microbial community structure and diversity, including reversing changes in the phyla Bacteroidetes, Proteobacteria, and Firmicutes, increasing 'beneficial' genera, and decreasing potential pathogens such as Lachnoclostridium, Acinobacter, and Serratia. Arginine-proline metabolism was significantly different between the colitis-treated and untreated groups. In the colon mucosa and RAW264.7 macrophage, resveratrol regulated arginine metabolism towards colon protection by increasing Arg1 and Slc6a8 and decreasing iNOS., Conclusion: This uncovers a previously unknown mechanism of resveratrol treatment in IBD and provides the microbiota-macrophage-arginine metabolism axis as a potential therapeutic target for intestinal inflammation., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Airway management failure is associated with increased perioperative morbidity and mortality. Airway-related complications can be significantly reduced if difficult laryngoscopy is predicted with high accuracy. Currently, there are no large-sample studies on difficult airway assessments in Chinese populations. An airway assessment model based on the Chinese population is urgently needed to guide airway rescue strategy., Methods: This prospective nested case-control study took place in a tertiary hospital in Shanghai, China. Information on 10,549 patients was collected, and 8,375 patients were enrolled, including 7,676 patients who underwent successful laryngoscopy and 699 patients who underwent difficult laryngoscopy. The baseline characteristics, medical history, and bedside examinations were included as predictor variables. Laryngoscopy was defined as 'successful laryngoscopy' based on a Cormack-Lehane Grades of 1-2 and as 'difficult laryngoscopy' based on a Cormack-Lehane Grades of 3-4. A model was developed by incorporating risk factors and was presented in the form of a nomogram by univariate logistic regression, least absolute shrinkage and selection operator, and stepwise logistic regression. The main outcome measures were area under the curve (AUC), sensitivity, and specificity of the predictive model., Result: The AUC value of the prediction model was 0.807 (95% confidence interval [CI]: 0.787-0.828), with a sensitivity of 0.730 (95% CI, 0.690-0.769) and a specificity of 0.730 (95% CI, 0.718-0.742) in the training set. The AUC value of the prediction model was 0.829 (95% CI, 0.800-0.857), with a sensitivity of 0.784 (95% CI, 0.73-0.838) and a specificity of 0.722 (95% CI, 0.704-0.740) in the validation set., Conclusion: Our model had accurate predictive performance, good clinical utility, and good robustness for difficult laryngoscopy in the Chinese 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., (Copyright © 2023 Jin, Pei, Cao, Ji, Xia and Jiang.)

Midkine plays a critical role in angiogenesis by regulating the vascular endothelial growth factor (VEGF) signalling pathway, which is known to be associated with psoriasis pathogenesis. However, research on midkine-psoriasis relationship remains limited. The objective of this study was to detect midkine expression in psoriasis and investigate its potential role in the disease. Midkine expression was measured using immunohistochemistry and ELISA. Effects of midkine on HaCaT cell proliferation, VEGF-A production and signalling pathways were assessed using CCK8, RT-PCR and WB. Scratch and in vitro tube formation tests were used to evaluate the effects of HaCaT-cell-activated midkine on the migration and tube formation of human dermal microvascular endothelial cells. Murine psoriasiform models were injected with midkine recombinant protein and midkine monoclonal antibody to investigate skin lesions, tissue sections and dermal microvessel density. Levels of midkine significantly increased in both lesions and serum of patients with psoriasis. Serum expression of midkine decreased after treatment and a positive correlation was found between midkine and disease severity. Midkine promoted HaCaT cell proliferation and VEGF-A production. The Notch2/HES1/JAK2-STAT5A pathway expression increased after midkine treatment of HaCaT cells. The supernatant of HaCaT cells treated with midkine promoted HMEC-1 migration and angiogenesis in vitro. Recombinant midkine protein exacerbated psoriasiform lesions with increased expressions of VEGF-A and microvessel density, while midkine monoclonal antibody alleviated psoriasis lesions. Midkine may have a significant impact on psoriasis angiogenesis by regulating VEGF-A expression through the Notch2/HES1/JAK2-STAT5A pathway, highlighting a potential therapeutic target for psoriasis treatment., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Background: Growing evidence has shown that gut microbiome composition is associated with breast cancer (BC), but the causality remains unknown. We aimed to investigate the link between BC prognosis and the gut microbiome at various oestrogen receptor (ER) statuses., Methods: We performed a genome-wide association study (GWAS) to analyse the gut microbiome of BC patients, the dataset for which was collected by the Breast Cancer Association Consortium (BCAC). The analysis was executed mainly via inverse variance weighting (IVW); the Mendelian randomization (MR) results were verified by heterogeneity tests, sensitivity analysis, and pleiotropy analysis., Results: Our findings identified nine causal relationships between the gut microbiome and total BC cases, with ten and nine causal relationships between the gut microbiome and ER-negative (ER-) and ER-positive (ER+) BC, respectively. The family Ruminococcaceae and genus Parabacteroides were most apparent among the three categories. Moreover, the genus Desulfovibrio was expressed in ER- BC and total BC, whereas the genera Sellimonas, Adlercreutzia and Rikenellaceae appeared in the relationship between ER + BC and total BC., Conclusion: Our MR inquiry confirmed that the gut microbiota is causally related to BC. This further explains the link between specific bacteria for prognosis of BC at different ER statuses. Considering that potential weak instrument bias impacts the findings and that the results are limited to European females due to data constraints, further validation is crucial., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Introduction: The aim of the study was to examine the association between frailty and osteoarthritis., Methods: We conducted a cross-sectional study in the National Health and Nutrition Examination Survey, while logistic regression was used to explore the association of the two. Mendelian randomization (MR) study was used to explore the causal relationship between the two., Results: In the cross-sectional study, logistic regression analysis showed that odds ratio (OR) (95% CI) value was 1.07 (1.05, 1.08). In the MR study, the inverse-variance weighting (IVW) results showed OR (95% CI) value of 1.69 (1.01-2.83)., Conclusions: There is both a correlation and a causal relationship between frailty and osteoarthritis, and frailty may be a potentially better response than age to osteoarthritis., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2023 Termedia & Banach.)

Background: Unanticipated difficult mask ventilation (DMV) is a potentially life-threatening event in anesthesia. Nevertheless, predicting DMV currently remains a challenge. This study aimed to verify whether three dimensional (3D) facial scans could predict DMV in patients scheduled for general anesthesia., Methods: The 3D facial scans were taken on 669 adult patients scheduled for elective surgery under general anesthesia. Clinical variables currently used as predictors of DMV were also collected. The DMV was defined as the inability to provide adequate and stable ventilation. Spatially dense landmarks were digitized on 3D scans to describe sufficient details for facial features and then processed by 3D geometric morphometrics. Ten different machine learning (ML) algorithms, varying from simple to more advanced, were introduced. The performance of ML models for DMV prediction was compared with that of the DIFFMASK score. The area under the receiver operating characteristic curves (AUC) with its 95% confidence interval (95% CI) as well as the specificity and sensitivity were used to evaluate the predictive value of the model., Results: The incidence of DMV was 35/669 (5.23%). The logistic regression (LR) model performed best among the 10 ML models. The AUC of the LR model was 0.825 (95% CI, 0.765-0.885). The sensitivity and specificity of the model were 0.829 (95% CI, 0.629-0.914) and 0.733 (95% CI, 0.532-0.819), respectively. The LR model demonstrated better predictive performance than the DIFFMASK score, which obtained an AUC of 0.785 (95% CI, 0.710-0.860) and a sensitivity of 0.686 (95% CI, 0.578-0.847). Notably, we identified a significant morphological difference in the mandibular region between the DMV group and the easy mask ventilation group., Conclusion: Our study indicated a distinct morphological difference in the mandibular region between the DMV group and the easy mask ventilation group. 3D geometric morphometrics with ML could be a rapid, efficient, and non-invasive tool for DMV prediction to improve anesthesia safety., 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 Pei, Jin, Cao, Ji, Xia and Jiang.)

The associations between social isolation, loneliness and the risk of mortality from all causes, cardiovascular disease (CVD) and cancer are controversial. We systematically reviewed prospective studies on the association between social isolation, loneliness and mortality outcomes in adults aged 18 years or older, as well as studies on these relationships in individuals with CVD or cancer, and conducted a meta-analysis. The study protocol was registered with PROSPERO (reg. no. CRD42022299959). A total of 90 prospective cohort studies including 2,205,199 individuals were included. Here we show that, in the general population, both social isolation and loneliness were significantly associated with an increased risk of all-cause mortality (pooled effect size for social isolation, 1.32; 95% confidence interval (CI), 1.26 to 1.39; P < 0.001; pooled effect size for loneliness, 1.14; 95% CI, 1.08 to 1.20; P < 0.001) and cancer mortality (pooled effect size for social isolation, 1.24; 95% CI, 1.19 to 1.28; P < 0.001; pooled effect size for loneliness, 1.09; 95% CI, 1.01 to 1.17; P = 0.030). Social isolation also increased the risk of CVD mortality (1.34; 95% CI, 1.25 to 1.44; P < 0.001). There was an increased risk of all-cause mortality in socially isolated individuals with CVD (1.28; 95% CI, 1.10 to 1.48; P = 0.001) or breast cancer (1.51; 95% CI, 1.34 to 1.70; P < 0.001), and individuals with breast cancer had a higher cancer-specific mortality owing to social isolation (1.33; 95% CI, 1.02 to 1.75; P = 0.038). Greater focus on social isolation and loneliness may help improve people's well-being and mortality risk., (© 2023. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: Non-communicable diseases have become a major threat to public health, with cardiovascular diseases (CVDs) and cancer being the top two causes of death each year., Objective: Our objective is to evaluate the balanced association between the effect of red and processed meat intake on the risk of death and the effect of physical activity on the risk of mortality, where the risk of death includes all causes, CVDs, and cancers., Methods: We searched electronic databases, including PubMed, ISI Web of Science, Embase, and the Cochrane Library, for prospective studies reporting risk estimates for the association between the intake of red and processed meat, walking, and muscle-strengthening activity (MSA) and the risk of mortality from all causes, CVDs, and cancer. We extracted fully adjusted effect estimates from original studies and performed a summary analysis using the fixed and random-effect models., Results: A conventional meta-analysis showed that red meat and processed meat were positively associated with the risk of mortality, and daily steps and MSA were negatively associated with the risk of death. Further analysis of the dose-response relationship showed that a risk reduction (20%) from 39.5 min/week of MSA or 4100 steps/d was equivalent to an increased risk of all-cause mortality from a daily intake of 103.4 g/d of red meat or 50 g/d of processed meat. The risk was further decreased as the number of steps per day increased, but the risk reversed when the MSA exceeded the threshold (39.5 min/week)., Conclusions: Adherence to physical activity is an effective way to reduce the risk of mortality due to meat intake. However, the total intake of red meat and processed meat should be controlled, especially the latter. Walking is recommended as the main daily physical activity of choice, while MSAs are preferred when time is limited, but it should be noted that longer MSAs do not provide additional benefits.

Background: Gastric cancer (GC) is one of the most common malignancies, with a low 5-year survival rate. However, if diagnosed at an early stage, it can be cured by endoscopic treatment and has a good prognosis. While gastrointestinal X-ray and upper endoscopy are used as national GC screening methods in some GC high-risk countries, such as Japan and Korea, their radiation exposure, invasiveness, and high cost suggest that they are not the optimal tools for early detection of GC in many countries. Therefore, a cost-effective, and highly accurate method for GC early detection is urgently needed in clinical settings. DNA methylation plays a key role in cancer progression and metastasis and has been demonstrated as a promising marker for cancer early detection. Aims and methods: This review provides a comprehensive overview of the current status of DNA methylation markers associated with GC, the assays developed for GC early detection, challenges in methylation marker discovery and application, and the future prospects of utilizing methylation markers for early detection of GC. Through our analysis, we found that the currently reported DNA methylation markers related to GC are mainly in the early discovery stage. Most of them have only been evaluated in tissue samples. The majority of non-invasive assays developed based on blood lack standardized sampling protocols, pre-analytical procedures, and multicenter validation, and they exhibit insufficient sensitivity for early-stage GC detection. Meanwhile, the reported GC DNA methylation markers are generally considered pan-cancer markers. Conclusion: Therefore, future endeavors should focus on identifying additional methylation markers specific to GC and establishing non-invasive diagnostic assays that rely on these markers. These assays should undergo multicenter, large-scale prospective validation in diverse populations., 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 Xue, Huang, Pei, Wang and Dai.)

Background: Unsuccessful airway management is associated with increased perioperative morbidity and mortality. Difficult laryngoscopy is a leading cause of unanticipated difficult airways and presents a challenge for anesthesiologists. Airway ultrasound assessment can be used as a priority diagnostic strategy for difficult laryngoscopy because of its diagnostic performance in difficult airways. This study was designed to develop a comprehensive model based on multivariate statistical analysis (including bedside examination tests and ultrasonography) for difficult laryngoscopy., Methods: This study was conducted from December 27, 2021, to September 16, 2022. All patients underwent an airway ultrasonographic measurement with a standard operating procedure. The baseline characteristics and bedside examination tests were also recorded. Laryngoscopy with a Cormack-Lehane (CL) grade of 1-2 was defined as "easy laryngoscopy", whereas "difficult laryngoscopy" was based on a CL grade of 3-4. The prediction model was built by using baseline characteristics, bedside examination tests, and ultrasonographic measurements as independent variables and easy/difficult laryngoscopy as the dependent variable., Results: A total of 516 patients were eligible, and 456 patients were finally enrolled in the study. A 4-variable analysis, including inter-incisor gap (IIG), thyromental distance (TMD), the distance from the skin to the tongue root, and airway-related diseases, was performed to construct the optimum prediction model. The area under curve (AUC) value of the prediction model was 0.933 [95% confidence interval (CI): 0.770 to 0.935] in the training set and 0.956 (95% CI: 0.915 to 0.997) in the validation set., Conclusions: The comprehensive model and nomogram, especially the integration of tongue root thickness, can predict the risk of difficult laryngoscopy more accurately and reliably than any other screening method alone, allowing for reasonable individualized regimen decision-making., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-23-95/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

In recent years, immune checkpoint blockade (ICB) therapy has become an important treatment strategy for gastrointestinal tumors, however, it only benefits about 1/3 of patients. Since the microbiome has been shown to play an important role in the human body for a long time, a growing number of studies are focusing on its relationship to ICB therapy in cancer, specifically how intestinal microbes affect the efficacy of immune checkpoint inhibitors (ICIs) therapy in patients. On this basis, probiotic interventions, fecal microbiota transplantation (FMT), dietary interventions, and other methods which improve or maintain the structure of the intestinal flora have attracted widespread attention. This article discusses the four aspects of the microbiome, ICB, combined treatment of gastrointestinal tumors, and regulation of gut microbiome. Particularly, the discussion focuses on the contribution of probiotic intervention in improving the therapeutic effect of ICIs to prolong the survival time of patients and reduce the severity of immune-related adverse effects (irAEs)., (Copyright ©2023 Chinese Journal of Cancer Research. All rights reserved.)

Embelin is a natural benzoquinone compound that displays a beneficial effect in various inflammatory-related diseases. However, the effect of embelin on degeneration of intervertebral disc (IDD), a chronic inflammatory disorder, has not been reported. This study was attempted to explore the therapeutic action of embelin on IDD in vitro. Network pharmacology analysis was performed for evaluating the link between embelin and IDD. The human nucleus pulposus cells (NPCs) were stimulated with IL-1β to induce inflammation. Cell viability of NPCs was assessed by CCK-8 assay. Western blotting was conducted to detect the expression levels of PI3K, p-PI3K, Akt, p-Akt, cleaved caspase-3, caspase-3, Bax, Bcl-2, p65 and p-p65. Apoptotic deaths of NPCs were examined by TUNEL assay. The production of COX-2, IL-6, IL-8, and TNF-α was examined by ELISA. It can be seen that 16 overlapping genes were selected from 109 possible targets of embelin and 342 possible targets of IDD. KEGG pathway enrichment analysis showed that the PI3K/Akt signaling pathway was a close link between embelin and IDD. We found that embelin dose-dependently improved the cell viability in IL-1β-stimulated NPCs. Embelin elevated the relative levels of p-PI3K/PI3K and p-Akt/Akt in IL-1β-stimulated NPCs. IL-1β induced a significant increase in apoptotic deaths of NPCs, which was attenuated by embelin treatment. IL-1β-induced alternations in expression levels of apoptotic-related proteins including cleaved caspase-3, Bax and Bcl-2 were prevented by embelin treatment. Pretreatment with LY294002 (an inhibitor of PI3K) reversed the inhibitory effect of embelin on IL-1β-induced apoptosis in NPCs. Embelin treatment caused inhibitory effects on the IL-1β-stimulated production of COX-2, IL-6, IL-8, and TNF-α, which were abolished by LY294002 treatment. Furthermore, embelin treatment prevented IL-1β-induced phosphorylation of p65 in NPCs, while LY294002 elevated the embelin-caused decrease in p-p65/p65 level. Overall, embelin protected human NPCs against IL-1β-stimulated apoptosis and inflammation by regulating the PI3K/Akt signaling pathway. These findings provided new ideas for the clinical usage of embelin in the prevention and treatment of IDD., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Introduction: The study aimed at screening indicators with differential diagnosis values and investigating the characteristics of laboratory tests in COVID-19 patients., Methodology: All the laboratory tests from COVID-19 patients and non-COVID-19 patients in this cohort were included. Test values from the groups during the course, days 1-7, and days 8-14 were analyzed. Mann-Whitney U test, univariate logistic regression analysis, and multivariate regression analysis were performed. Regression models were established to verify the diagnostic performance of indicators., Results: 302 laboratory tests were included in this cohort, and 115 indicators were analyzed; the values of 61 indicators had significant differences (p < 0.05) between groups, and 23 indicators were independent risk factors of COVID-19. During days 1-7, the values of 40 indicators had significant differences (p < 0.05) between groups, while 20 indicators were independent risk factors of COVID-19. During days 8-14, the values of 45 indicators had significant differences (p < 0.05) between groups, and 23 indicators were independent risk factors of COVID-19. About 10, 12, and 12 indicators showed significant differences (p < 0.05) in multivariate regression analysis in different courses respectively, and the diagnostic performance of the model from them was 74.9%, 80.3%, and 80.8% separately., Conclusions: The indicators obtained through systematic screening have preferable differential diagnosis values. Compared with non-COVID-19 patients, the screened indicators indicated that COVID-19 patients had more severe inflammatory responses, organ damage, electrolyte and metabolism disturbance, and coagulation disorders. This screening approach could find valuable indicators from a large number of laboratory test indicators., Competing Interests: No Conflict of Interest is declared, (Copyright (c) 2023 Lei Chen, Gaojing Qu, Guoxin Huang, Meiling Zhang, Junwen Chen, Dengru Wang, Ying Liu, Bin Pei.)

Background: Clinical rehabilitation for brachial plexus injury is difficult in terms of chronic pain and dysfunction. Physiotherapy is considered a routine intervention for rehabilitation. Common physical therapy may require a variety of instruments. One approach that does not need instruments, but belongs to the field of complementary and alternative medicine, is naprapathy. Naprapathy, also called Tuina in China, has been applied in rehabilitation after brachial plexus injury for a long time. Naprapathy can relieve chronic neuropathic pain, promote local blood circulation, and improve body edema. Naprapathy can passively help improve motor functions in patients with peripheral nerve injury. However, the efficacy of naprapathy in improving rehabilitation after brachial plexus injury is unclear., Objective: This study aims to evaluate the additional value of naprapathy when combined with conventional physical therapy for the treatment of brachial plexus injury., Methods: This will be a single-center randomized controlled trial. A total of 116 eligible patients with brachial plexus injury will be randomly divided into an experimental group (naprapathy plus physical therapy group) or a control group (physical therapy group). The participants will be followed up for 4 weeks of treatment. Observation outcomes will include the visual analog scale score, upper limb index, electromyography findings, and adverse reactions, among others. The measuring points for outcomes will be the baseline and the completion of treatment. In addition, a quality control group independent from the research team will be set up to control the quality of the trial. Finally, the data will be analyzed using SPSS software (version 21.0; IBM Corp)., Results: The study is recruiting participants. The first participant was enrolled in September 2021. As of January 2023, a total of 100 participants have been enrolled. The trial is expected to be completed by September 2023. The study protocol was approved by the Ethics Review Committee of Yue Yang Hospital affiliated with the Shanghai University of Traditional Chinese Medicine (2021-012)., Conclusions: One limitation of this trial is that we will be unable to achieve strict double-blinding because of the features of naprapathy. The trial aims to contribute reliable evidence for decision-making in naprapathy for treating brachial plexus injury., Trial Registration: Chinese Clinical Trial Registry ChiCTR2100043515; http://www.chictr.org.cn/showproj.aspx?proj=122154., International Registered Report Identifier (irrid): DERR1-10.2196/46054., (©Bin Xiao, Lishu Zhao, Yong Huang, Anqi Ma, Baoshun Pei, Zhengyu Li, Fei Gu. Originally published in JMIR Research Protocols (https://www.researchprotocols.org), 29.05.2023.)

Uncoordinated 51-like kinase 1 (ULK1) is an essential part involved in autophagy to maintain cell viability and homeostasis. Herein, the expression levels of ULK1 in colon cancer (CC) were investigated, and its clinicopathological features and potential function were analyzed. Data of ULK1 were obtained from a public database. UCSC XENA RNAseq data were uniformly processed by using the Toil process. STRING was employed for identification of co-expression genes and development of PPI networks whose interaction scores exceeded 0.4. The level of immune cells for tumor infiltration was calculated by means of single-sample GSEA (ssGSEA) on the basis of mRNA data of CC. The ULK1 expression was upregulated compared with both paired and unpaired normal tissues. The mRNA expression of ULK1 was upregulated in CC patients with lymph node metastasis, lymphatic invasion, and pathological stages of 3 and 4. The disease-specific survival (DSS), progression-free interval (PFI), and the overall survival (OS) of patients with upregulated mRNA expression of ULK1 were drastically reduced. Functionally, any changes related to the biological process of ULK1 may be related to macroautophagy, autophagosome organization and autophagosome assembly. As a co-expressed gene (CEG), ATG101 was up-regulated in CC tissues and indicated poor survival. ULK1 is closely related to immune cells. ULK1 expression is upregulated in CC cells and upregulation of ULK1 may serve as an accurate prognostic factor, thereby providing novel intervention targets for therapy.

This paper introduces a new type of steel-concrete composite pylon that has been applied to Nanjing Fifth Yangtze River Bridge (a three-pylon cable-stayed bridge with a main span of 600 m). For this new type of pylon, the steel shells are connected with concrete through PBL shear connectors and studs, and the inner steel shells are connected with the outer steel shells by angle steels. Numerical analysis and full-scale model tests show that the pylon structure exhibits excellent mechanical properties and construction performance. The application of BIM technology, the research and development of special spreaders and construction platforms ensure the precise installation of structures. Highly factory-manufactured modular assembly of the reinforced steel shell structure can effectively reduce the intensity and difficulty of on-site operations, and improve the quality of the project, with low construction risks. Whereas, the successful application of this steel-concrete-steel sandwich composite pylon marks the formation of a complete set of construction technology of steel-concrete-steel sandwich composite pylon, which can be widely used in similar bridges., (© 2023. The Author(s).)

Background: Gastric intestinal metaplasia (IM) is the key link of gastric precancerous lesions. Ferroptosis is a novel form of programmed cell death. However, its impact on IM is unclear. The focus of this study is to identify and verify ferroptosis-related genes (FRGs) that may be involved in IM by bioinformatics analysis. Materials and methods: Differentially expressed genes (DEGs) were obtained from microarray dataset GSE60427 and GSE78523 downloaded from Gene Expression Omnibus (GEO) database. Differentially expressed ferroptosis-related genes (DEFRGs) were obtained from overlapping genes of DEGs and FRGs got from FerrDb. DAVID database was used for functional enrichment analysis. Protein-protein interaction (PPI) analysis and Cytoscape software were used to screen hub gene. In addition, we built a receiver operating characteristic (ROC) curve and verified the relative mRNA expression by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Finally, the CIBERSORT algorithm was used to analyze the immune infiltration in IM. Results: First, a total of 17 DEFRGs were identified. Second, a gene module identified by Cytoscape software was considered as hub gene: PTGS2, HMOX1, IFNG, and NOS2. Third, ROC analysis showed that HMOX1 and NOS2 had good diagnostic characteristics. qRT-PCR experiments confirmed the differential expression of HMOX1 in IM and normal gastric tissues. Finally, immunoassay showed that the proportion of T cells regulatory (Tregs) and macrophages M0 in IM was relatively higher, while the proportion of T cells CD4 memory activated and dendritic cells activated was lower. Conclusion: We found significant associations between FRGs and IM, and HMOX1 may be diagnostic biomarkers and therapeutic targets for IM. These results may enhance our understanding of IM and may contribute to its treatment., 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 Song, Li, Zhang, Yang, Pei, Liu, Wang, Dong, Sun, Fan and Li.)

Phytoplasmas are insect-borne bacterial pathogens capable of secreting effectors into host cells and interfering with host plant defense response processes. Previous studies have found that the Candidatus Phytoplasma tritici effector SWP12 binds to and destabilizes the wheat transcription factor TaWRKY74, increasing wheat susceptibility to phytoplasmas. Here, we used a Nicotiana benthamiana transient expression system to identify two key functional sites of SWP12 and screened a series of truncated mutants and amino acid substitution mutants to determine whether they inhibit Bax-induced cell death. Using a subcellular localization assay and online structure analysis websites, we found that structure rather than intracellular localization probably affects the function of SWP12. D33A and P85H are two inactive substitution mutants, neither of which interacts with TaWRKY74, and P85H does not inhibit Bax-induced cell death, suppress flg22-triggered reactive oxygen species (ROS) bursts, degrade TaWRKY74, or promote phytoplasma accumulation. D33A can weakly suppress Bax-induced cell death and flg22-triggered ROS bursts and degrade a portion of TaWRKY74 and weakly promote phytoplasma accumulation. S53L, CPP, and EPWB are three SWP12 homolog proteins from other phytoplasmas. Sequence analysis revealed that D33 was conserved in these proteins, and they exhibited the same polarity at P85. Transient expression in N. benthamiana showed that these proteins could inhibit Bax-induced cell death and suppress ROS bursts. Our findings clarified that P85 and D33 of SWP12 play critical and minor roles, respectively, in suppressing the plant defense response and that they play a preliminary role in determining the functions of homologous proteins., Competing Interests: Conflict of interest The authors declare that they have no conflicts of interest with the contents of this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)