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A pyridine–tricarboxylic acid, 4-(6-carboxy-pyridin-3-yl)-isophthalic acid (H3cpia), was used as a versatile building block to synthesize three novel coordination polymers under hydrothermal conditions and formulated as [Mn8(μ3-Hcpia)2 (μ6-cpia)4(Hbiim)2(H2O)6]n·6nH2O (1), [Cu3(μ4-cpia)2(bipy)2(H2O)2]n·4nH2O (2), and [Ni3(μ3-cpia)2(dpe)3(H2O)2]n·4nH2O (3). Three supporting ligands, 2,2′-biimidazole (H2biim), 2,2′-bipyridine (bipy), and 1,2-di(4-pyridyl)ethane (dpe), were used in the synthesis. The structures of the studied products 1–3 varied significantly, ranging from a 1D chain (2) to 2D sheets (1 and 3). Furthermore, these compounds were evaluated as heterogeneous catalysts for the Henry reaction, achieving high product yields under optimized conditions. In addition, we investigated various reaction parameters and substrate scopes, and assessed the feasibility of catalyst recycling. This thorough investigation’s results highlight the versatility of H3cpia as a tricarboxylate building block in the formation of functional coordination polymers.

Abstract We present four open-source datasets that provide results of density functional theory (DFT) calculations of ground-state properties of refractory solid solution binary alloys niobium-tantalum (NbTa), niobium-vanadium (NbV), tantalum-vanadium (TaV), and ternary alloys NbTaV ordered in body-centered-cubic (BCC) structures with 128 Bravais lattice sites. The first-principles code used to run the calculations is the Vienna Ab-Initio Simulation Package. The calculations have been collected by uniformly sampling chemical compositions across the entire compositional range. For each chemical composition, the calculations have been run for 100 randomized arrangements of the constituents on the BCC lattice sites. This sampling methodology resulted in running DFT simulations for a total of 3,100 randomized atomic configurations over 31 chemical compositions for each of the three binary alloys Nb-Ta, Nb-V, Ta-V, and a total of 10,500 randomized atomic structures over 105 chemical compositions for the ternary alloys Nb-Ta-V. For each atomic configuration, geometry optimization has been performed, and the data released contains information about each step of geometry optimization for each atomic configuration.

Abstract To assess whether the radiomics signature of pericoronary adipose tissue (PCAT) from coronary computed tomography angiography (CCTA) can distinguish between perimenopausal women with coronary heart disease (CHD) and those without coronary artery disease (CAD). This single-center retrospective case–control study comprised 140 perimenopausal women with CHD presenting with chest pain who underwent CCTA within 48 h of admission. They were matched with 140 control patients presenting with chest pain but without CAD, based on age, risk factors, radiation dose and CT tube voltage. For all participants, PCAT around the proximal right coronary artery was segmented, from which radiomics features and the fat attenuation index (FAI) were extracted and analyzed. Subsequently, corresponding models were developed and internally validated using Bootstrap methods. Model performance was assessed through measures of identification, calibration, and clinical utility. Using logistic regression analysis, an integrated model that combines clinical features, fat attenuation index and radiomics parameters demonstrated enhanced discrimination ability for perimenopausal CHD (area under the curve [AUC]: 0.80, 95% confidence interval [CI]:0.740–0.845). This model outperformed both the combination of clinical features and PCAT attenuation (AUC 0.67, 95% CI 0.602–0.727) and the use of clinical features alone (AUC 0.66, 95% CI 0.603–0.732). Calibration curves for the three predictive models indicated satisfactory fit (all p > 0.05). Moreover, decision curve analysis demonstrated that the integrated model offered greater clinical benefit compared to the other two models. The CCTA-based radiomics signature derived from the PCAT model outperforms the FAI model in differentiating perimenopausal CHD patients from non-CAD individuals. Integrating PCAT radiomics with the FAI could enhance the diagnostic accuracy for perimenopausal CHD.

Abstract Immunotherapy confers little to no benefit in the treatment of microsatellite stable (MSS) metastatic colorectal cancer (mCRC). Mechanistic insights suggested that epidermal growth factor receptor (EGFR) antibody plus irinotecan might augment the tumor immune response in mCRC. Therefore, we conducted a proof-of-concept, single-arm, phase 2 study (ChiCTR identifier: ChiCTR2000035642) of a combination treatment regimen including tislelizumab (anti-PD-1), cetuximab (anti-EGFR) and irinotecan in 33 patients with MSS and RAS wild-type (WT) mCRC who were previously treated with ≥2 lines of therapy. The primary endpoint was met, with a confirmed objective response rate of 33%. As secondary endpoints, the disease control rate was 79%, and the median progression-free survival and overall survival were 7.3 and 17.4 months respectively. Among the 33 patients, 32 (97.0%) had treatment-related adverse events (AEs). Three (9.1%) reported grade ≥ 3 AEs, including rash (n = 1), neutropenia (n = 2). The post-hoc evaluation of dynamic circulating tumor DNA using next generation sequencing and the analysis of peripheral immune proteomics landscape using Olink revealed that lower variant allele frequency (VAF) at baseline, greater reduction in VAF on treatment, and a hot peripheral macroenvironment were associated with the treatment response independently. Our study showed the antitumor activity of tislelizumab, cetuximab, and irinotecan combination with a tolerable safety profile in previously treated MSS and RAS WT mCRC.

Abstract The SARS-CoV-2 Omicron variant sparked the largest wave of infections worldwide. Mainland China eased its strict COVID-19 measures in late 2022 and experienced two nationwide Omicron waves in 2023. Here, we investigated lineage distribution and virus evolution in Guangdong, China, 2022-2023 by comparing 5813 local viral genomes with the datasets from other regions of China and worldwide. Additionally, we conducted three large-scale serological surveys involving 1696 participants to measure their immune response to the BA.5 and XBB.1.9 before and after the corresponding waves. Our findings revealed the Omicron variants, mainly the BA.5.2.48 lineage, causing infections in over 90% of individuals across different age groups within a month. This rapid spread led to the establishment of widespread immunity, limiting the virus’s ability to further adaptive mutation and dissemination. While similar immune responses to BA.5 were observed across all age groups after the initial wave, children aged 3 to 11 developed a stronger cross immune response to the XBB.1.9 strain, possibly explaining their lower infection rates in the following XBB.1 wave. Reinfection with Omicron XBB.1 variant triggered a more potent neutralizing immune response among older adults. These findings highlight the impact of age-specific immune responses on viral spread in potential future waves.

Abstract This study explores the association between LE8 scores and mortality risks among individuals diagnosed with cardiovascular disease (CVD). Utilizing data from the NHANES conducted between 2005 and 2018, survey-weighted multivariable Cox proportional hazards regression models were utilized. Life’s Essential 8 (LE8) scores dose–response associations were assessed using restricted cubic spline regression. Sub-analyses were performed for different categories of CVD. The study consisted of 2164 participants diagnosed with CVD, ranging in age from 20 to 80 years (weighted mean [SE] age, 61.47 [0.34] years; The average total LE8 was 64.97 [0.54]. 499 participants experienced mortality, with 350 deaths attributed to CVD. After accounting for potential covariates, LE8 score was found to be associated with a decreased both all-cause mortality (OR 0.34, CI 0.22–0.51) and CVD mortality (OR 0.40, CI 0.23–0.68). A survey-weighted multivariable Cox model with restricted cubic splines identified the lowest all-cause mortality (P

Abstract With the ongoing challenge of air pollution posing serious health and environmental threats, particularly in rapidly industrializing regions, accurate forecasting and effective pollutant identification are crucial for enhancing public health and ecological stability. This study aimed to optimize air quality management through the prediction of the Air Quality Index (AQI) and identification of air pollutants. Our study spans nine representative cities (Hohhot, Yinchuan, Lanzhou, Beijing, Taiyuan, Xi’an, Shanghai, Nanjing, Wuhan) in China, with data collected from January 1, 2015, to November 30, 2021. We proposed a new model for daily AQI prediction, termed VMD-CSA-CNN-LSTM, which employed advanced machine learning techniques, including convolutional neural networks (CNN) and long short-term memory (LSTM) networks, and leveraged the chameleon swarm algorithm (CSA) for hyperparameter optimization, integrated through a variational mode decomposition approach. The model was developed using data from Lanzhou, with a split ratio of 8:1:1 into training, validation, and test sets, achieving an RMSE of 2.25, MAPE of 0.02, adjusted R-squared of 98.91%, and training efficiency of 5.31%. The model was further externally validated in the other eight cities, yielding comparable results, with an adjusted R-squared above 96%, MAPE below 0.1, and RMSE below 7.5. Additionally, we employed a random forest algorithm to identify the primary pollutants contributing to AQI levels. Our results indicated that PM2.5 was the most significant pollutant in Beijing, Taiyuan, and Xi’an, while PM10 was dominant in Hohhot, Yinchuan, and Lanzhou. In Shanghai, Nanjing, and Wuhan, both PM2.5 and PM10 were critical, with ozone also identified as a major air pollutant. This study not only advances the predictive accuracy of AQI models but also aids policymakers by providing a reliable tool for air quality management and strategic planning aimed at pollution reduction. The integration of these advanced computational techniques into environmental monitoring practices offers a promising avenue for enhancing air quality and mitigating pollution-related risks.

Abstract Background Currently, the prevalence of obesity is on the rise annually. Bariatric surgery stands out as the most efficacious approach for addressing obesity. Obese patients are more prone to experience moderate to severe pain after surgery due to lower pain thresholds. Regional block, as an important component of multimodal analgesia in bariatric surgery, is crucial in reducing opioid consumption and alleviating postoperative pain in patients undergoing bariatric surgery. Transversus abdominis plane block (TAPB) has gained widespread utilization in bariatric surgery; however, its limitation of inadequate reduction of visceral pain in obese patients remains a significant concern. Therefore, it is imperative to explore new and more efficient strategies for analgesia. Quadratus lumborum block (QLB) has emerged as a popular nerve block in recent years, frequently utilized in conjunction with general anesthesia for abdominal surgery. In the cadaver study of QLB, it was confirmed that the dye level could reach up to T6 when using the subcostal anterior quadratus lumborum muscle approach, which could effectively reduce the incision pain and visceral pain of bariatric surgery patients during the perioperative period. However, there is currently a lack of research on the use of subcostal anterior QLB in patients undergoing bariatric surgery. Our study aims to investigate whether subcostal anterior QLB can provide superior perioperative analgesic efficacy for bariatric surgery under general anesthesia compared to TAPB, leading to reduced postoperative opioid consumption and a lower incidence of postoperative nausea and vomiting (PONV). Methods and design This study is a prospective, randomized controlled trial aiming to recruit 66 patients undergoing bariatric surgery. The participants will be randomly allocated into two groups in a 1:1 ratio: subcostal anterior QLB group (n = 33) and TAPB group (n = 33). The study aims to investigate the efficacy of subcostal anterior QLB and TAPB in obese patients who are scheduled to undergo bariatric surgery. Our primary outcome is to observe the amount of opioids used in the two groups 24 h after operation. The secondary outcomes included VAS of pain during rest/activity after operation, the type and dose of additional analgesics, the occurrence and severity of PONV, the type and dose of additional antiemetic drugs, postoperative anesthesia care unit (PACU) time, time of first postoperative exhaust, time to first out of bed activity, time to first liquid diet and postoperative admission days. Discussion Opioid analgesics are prone to causing adverse reactions such as nausea, vomiting, and respiratory depression, especially in obese patients. Multimodal analgesia, including nerve block, can effectively reduce the dose of opioids and alleviate their adverse effects. Currently, TAPB is the most prevalent nerve block analgesia method for abdominal surgery. Recent studies have indicated that subcostal anterior QLB offers advantages over TAPB, including a wider block plane, faster onset, and longer maintenance time. It is not clear which of the two nerve block analgesia techniques is better for postoperative analgesia in patients undergoing bariatric surgery. Our objective in this investigation is to elucidate the superior method between TAPB and subcostal anterior QLB for postoperative pain management in bariatric surgery. Trial registration ChiCTR ChiCTR2300070556. Registered on 17 April 2023.

Objective Although the advantages of postoperative braces have been verified in many fields, it is not clear whether postoperative braces can help reduce patients' adverse psychological emotions such as kinesiophobia, anxiety, and depression. This study aims to analyze whether the use of a postoperative brace helps reduce adverse psychological emotions in adolescent idiopathic scoliosis (AIS) patients undergoing spinal deformity surgeries. Methods All consecutive patients who underwent spinal corrective surgeries at our institution between April 2023 and July 2023 formed the prospective cohort. Outcome measures were collected in the preoperative period, 3 months after surgery, and 6 months after surgery. All patients were assessed using the Tampa scale for kinesiophobia (TSK), the hospital anxiety and depression scale (HADS), and the numerical rating scale (NRS). A statistical model of propensity score matching was used to eliminate potential selection bias and maintain comparability. Multivariate linear regression models were used to determine the relationship between postoperative brace and adverse psychological emotions. Results After propensity score matching, this study ultimately enrolled 150 patients. There were no significant differences between the two groups in terms of demographic and perioperative variables. The fully adjusted model showed that the TSK scores of the non‐brace group at the 3‐month (ꞵ = 2.50, 95% CI 0.80–4.20, p = 0.005) and 6‐month follow‐up (ꞵ = 2.75, 95% CI 0.75–4.74, p = 0.007) were significantly higher than those of the brace group. The HADS score of the non‐brace group at the 3‐month follow‐up was significantly higher than that of the brace group (ꞵ = 1.75, 95% CI 0.28–3.22, p = 0.019). The NRS score of the non‐brace group at the 3‐month follow‐up was significantly higher than that of the brace group (ꞵ = 0.69, 95% CI 0.05–1.33, p = 0.034). At the 6‐month follow‐up, there were no significant difference for HADS score or NRS score between the two groups. Conclusion In the early postoperative period, the postoperative brace could provide AIS patients with psychological supports and help them reduce the frequency of adverse psychological emotions. The postoperative brace could continuously improve the fear of movement within 6 months after surgery, and help reduce anxiety, depression, and pain within 3 months after surgery.

Introduction: Morphological abnormalities of erythrocytes/red blood cells (RBCs), e.g., increased acanthocytes, in Parkinson’s disease (PD) have been reported previously, although the underlying mechanisms remain to be characterized. In this study, the potential roles of α-synuclein (α-syn), a protein critically involved in PD and highly abundant in RBCs, were studied in PD patients as well as in a PD mouse model. Methods: Transgenic [PAC-Tg (SNCAA53T), A53T] mice overexpressing A53T mutant α-syn and SNCA knockout mice were employed to characterize the effect of α-syn on RBC morphology. In addition to A53T and SNCA knockout mice, the morphology of RBCs of PD patients was also examined using scanning electron microscopy. The potential roles of α-syn were further investigated in cultured RBCs and mice. Results: Morphological abnormalities of RBCs and increased accumulation of aggregated α-syn on the RBC membrane were observed in PD patients. A similar phenomenon was also observed in A53T mice. Furthermore, while mice lacking α-syn expression showed a lower proportion of acanthocytes, treating RBCs derived from SNCA knockout mice with aggregated α-syn resulted in a higher percentage of acanthocytes. In a follow-up proteomic investigation, several major classes of proteins were identified as α-syn-associated proteins on the RBC membrane, seven of which were calcium-binding proteins. Applying aggregated α-syn to the RBC membrane directly induced extracellular calcium influx along with morphological changes; both observations were adequately reversed by blocking calcium influx. Conclusions: This study demonstrated that α-syn plays a critical role in PD-associated morphological abnormalities of RBCs, at least partially via a process mediated by extracellular calcium influx.

Low carbon medium manganese steel with chromium and molybdenum addition (4MnCM), alongside a control group without these additions (4Mn), was developed. The quenching (860 °C) and tempering (620 °C) heat treatment process was applied to both steel groups. The influence of Cr and Mo on the microstructure evolution and mechanical properties was examined. The findings revealed that, the low−temperature impact energy values (KV2) of 4MnCM at −60 and −84 °C were enhanced by 104 and 107 J, in comparison to 4Mn. The yield and tensile strength saw an increase of 100 MPa. The higher low-temperature toughness of 4MnCM is attributed, on one hand, to the addition of Cr and Mo, which inhibiting deformation twinning through enhances the stacking fault energy (SFE) of reversed austenite. On the other hand, it is due to the absence of coarse ε−martensite (ε−m) along the crack propagation path. Additionally, the phase transformation of reversed austenite occurs at the crack nucleation stage during the impact process of both steels, which helps alleviate stress concentration and increases the energy required for crack formation. The primary reason for the higher strength of 4MnCM lies in the significant enhancement of precipitation strengthening effects through the precipitation of M6C, M23C6 and Nb/TiC co-precipitation with M6C.

Abstract Elymus species, belonging to Triticeae tribe, is a tertiary gene pool for improvement of major cereal crops. Elymus sibiricus, a tetraploid with StH genome, is a typical species in the genus Elymus, which is widely utilized as a high-quality perennial forage grass in template regions. In this study, we report the construction of a chromosome-scale reference assembly of E. sibiricus line Gaomu No. 1 based on PacBio HiFi reads and chromosome conformation capture. Subgenome St and H were well phased by assisting with kmer and subgenome-specific repetitive sequence. The total assembly size was 6.929 Gb with a contig N50 of 49.518 Mb. In total, 89,800 protein-coding genes were predicted. The repetitive sequences accounted for 82.49% of the genome in E. sibiricus. Comparative genome analysis confirmed a major species-specific 4H/6H reciprocal translocation in E. sibiricus. The E. sibiricus assembly will be much helpful to exploit genetic resource of StH species in genus Elymus, and provides an important tool for E. sibiricus domestication.

Abstract Circulating cell-free DNA (cfDNA) in the peripheral blood is a promising biomarker for cancer diagnosis and prognosis. Somatic mutations identified in cancers have been used to detect therapeutic targets for clinical transformation and individualize drug selection, while germline variants can predict a patient’s risk of developing cancer and drug sensitivity. However, no platform has been developed to analyze, calculate, integrate, and friendly visualize these pan-cancer cfDNA mutations deeply. In this work, we performed panel sequencing encompassing 1,115 cancer-related genes across 16,659 cancer patients, spanning 27 cancer types. We detected 496 germline variants in leukocytes and 11,232 somatic mutations in the cfDNA of all patients. CPGV (Cancer Peripheral blood Gene Variations), a database constructed from this dataset, is the first pan-cancer cfDNA database that encompasses somatic mutations, germline variants, and further comparative analyses of mutations across different cancer types. It bears great promise to serve as a valuable resource for cancer research.

Abstract To the best of our knowledge, N6-Methyladenosine (m6A) exerts a significant role in the occurrence and development of various tumors. Gastric cancer (GC), originating from the mucosal epithelium in the digestive tract, is the fifth most common cancer and the third most common cause of cancer death around the world. Therefore, it is urgent to explore the specific mechanism of tumorigenesis of GC. As we all know, m6A modification as the most common RNA modification, is involved in the modification of mRNA and ncRNA at the post-transcriptional level, which played a regulatory role in various biological processes. As identified by numerous studies, the m6A modification are able to influence the proliferation, apoptosis, migration, and invasion of GC. What’s more, m6A modification are associated with EMT, drug resistance, and aerobic glycolysis in GC. m6A related-ncRNAs may be a valuable biomarker used by the prediction of GC diagnosis in the future. This review summarizes the role of m6A modification in the mechanism of gastric cancer, with the aim of identifying biological progress.

Abstract In this work, we test the cosmic distance duality relation (CDDR) by comparing the angular diameter distance (ADD) derived from the transverse Baryon Acoustic Oscillations (BAO) data with the luminosity distance (LD) from the Pantheon type Ia supernova (SNIa) sample. The binning method and Gaussian process are employed to match ADD data with LD data at the same redshift. First, we use nonparametric and parametric methods to investigate the impact of the specific prior values of the absolute magnitude $$M_\textrm{B}$$ M B from SNIa observations and the sound horizon scale $$r_\textrm{s}$$ r s from transverse BAO measurements on the CDDR tests. The results obtained from the parametric and non-parametric methods indicate that specific prior values of $$M_\textrm{B}$$ M B and $$r_\textrm{s}$$ r s lead to significant biases on the CDDR test. Then, to avoid these biases, we propose a method independent of $$M_\textrm{B}$$ M B and $$r_\textrm{s}$$ r s to test CDDR by considering the fiducial value of $$\kappa \equiv 10^{M_\textrm{B} \over 5}r_\textrm{s}$$ κ ≡ 10 M B 5 r s as a nuisance parameter and then marginalizing its influence with a flat prior in the analysis. No violation of the CDDR is found, and the transverse BAO measurement can be used as a powerful tool to verify the validity of CDDR in the cosmological-model-independent method.

Abstract NOP2, a member of the NOL1/NOP2/SUN domain (NSUN) family, is responsible for catalyzing the posttranscriptional modification of RNA through 5-methylcytosine (m5C). Dysregulation of m5C modification has been linked to the pathogenesis of various malignant tumors. Herein, we investigated the expression of NOP2 in lung adenocarcinoma (LUAD) tissues and cells, and found that it was significantly upregulated. Moreover, lentivirus-mediated overexpression of NOP2 in vitro resulted in enhanced migration and invasion capabilities of lung cancer cells, while in vivo experiments demonstrated its ability to promote the growth and metastasis of xenograft tumors. In contrast, knockdown of NOP2 effectively inhibited the growth and metastasis of lung cancer cells. RNA-sequencing was conducted to ascertain the downstream targets of NOP2, and the findings revealed a significant upregulation in EZH2 mRNA expression upon overexpression of NOP2. Subsequent validation experiments demonstrated that NOP2 exerted an m5C-dependent influence on the stability of EZH2 mRNA. Additionally, our investigations revealed a co-regulatory relationship between NOP2 and the m5C reader protein ALYREF in modulating the stability of EZH2 mRNA. Notably, the NOP2/EZH2 axis facilitated the malignant phenotype of lung cancer cells by inducing epithelial–mesenchymal transition (EMT) both in vitro and in vivo. Mechanistically, ChIP analysis proved that EZH2 counteracted the impact of NOP2 on the occupancy capacity of EZH2 and H3K27me3 in the promoter regions of E-cadherin, a gene crucial for regulating EMT. In a word, our research highlights the significant role of NOP2 in LUAD and offers novel mechanistic insights into the NOP2/ALYREF/EZH2 axis, which holds promise as a potential target for lung cancer therapy.

Abstract Objectives To investigate the clinical features and risk factors of Sjogren’s Syndrome (SS) patients suffering from oral candidiasis and to provide a foundation for the prevention and treatment of oral candidiasis in SS patients. Methods The medical records of 479 SS patients admitted to the Second Hospital of Shanxi Medical University from 2018 to 2020 were analysed to determine the clinical characteristics and risk factors that influence the occurrence of oral candidiasis infection in SS patients. Results Patients with oral candidiasis were older than those without oral candidiasis (P

Abstract. Background:. Psychological stress has been reported to be a potential risk factor for hypertension among females, but it remains unclear whether spousal chronic stress levels alter the risk of hypertension among women. We examined the associations between stress within the family and hypertension among married women. Methods:. Reproductive-aged women who were planning for pregnancy and their husbands were recruited from the National Free Pre-pregnancy Checkup Projects (NFPCP) across 31 provinces in China in 2016 and 2017. Perceived stress of wives or husbands was measured with a 5-point Likert-type scale, and assessed from three domains: work/life-related stress, economic stress, and overall stress. Multivariable-adjusted logistic regression models were used to assess the associations between stress status and the prevalence of hypertension. Results:. Of 10,027,644 couples, 261,098 (2.60%) women had hypertension. The results showed that higher stress levels among themselves or their husbands were associated with a higher prevalence of hypertension in women (Pfor trend

Abstract Background The occurrence, development, and outbreak of tea diseases and pests pose a significant challenge to the quality and yield of tea, necessitating prompt identification and control measures. Given the vast array of tea diseases and pests, coupled with the intricacies of the tea planting environment, accurate and rapid diagnosis remains elusive. In addressing this issue, the present study investigates the utilization of transfer learning convolution neural networks for the identification of tea diseases and pests. Our objective is to facilitate the accurate and expeditious detection of diseases and pests affecting the Yunnan Big leaf kind of tea within its complex ecological niche. Results Initially, we gathered 1878 image data encompassing 10 prevalent types of tea diseases and pests from complex environments within tea plantations, compiling a comprehensive dataset. Additionally, we employed data augmentation techniques to enrich the sample diversity. Leveraging the ImageNet pre-trained model, we conducted a comprehensive evaluation and identified the Xception architecture as the most effective model. Notably, the integration of an attention mechanism within the Xeption model did not yield improvements in recognition performance. Subsequently, through transfer learning and the freezing core strategy, we achieved a test accuracy rate of 98.58% and a verification accuracy rate of 98.2310%. Conclusions These outcomes signify a significant stride towards accurate and timely detection, holding promise for enhancing the sustainability and productivity of Yunnan tea. Our findings provide a theoretical foundation and technical guidance for the development of online detection technologies for tea diseases and pests in Yunnan.

Dielectric capacitors with high power density and fast charge-discharge speed play an essential role in the development of pulsed power systems. The increased demands for miniaturization and practicality of pulsed power equipment also necessitate the development of dielectric materials that possess high energy density while maintaining ultrahigh efficiency (η). In particular, ultrahigh efficiency signifies minimal energy loss, which is essential for practical applications but challenging to effectively mitigate. Here, we demonstrate a strategy of incorporating heterovalent elements into Ba(Zr0·1Ti0.9)O3, which contributes to achieving relaxor ferroelectric ceramics and reducing lattice strain, thereby improving the comprehensive energy storage performance. Finally, optimal energy storage performance is attained in 0.85Ba(Zr0·1Ti0.9)O3-0.15Bi(Zn2/3Ta1/3)O3 (BZT-0.15BiZnTa), with an ultrahigh η of 97.37% at 440 kV/cm (an advanced level in the lead-free ceramics) and an excellent recoverable energy storage density (Wrec) of 3.74 J/cm3. Notably, the BZT-0.15BiZnTa ceramics also exhibit exceptional temperature stability, maintaining fluctuations in Wrec within ∼10% and η consistently exceeding 90% across the wide temperature range of −55 °C to160 °C, and under a high electric field of 250 kV/cm. All these features demonstrate that the relaxor and lattice strain engineering strategies have been successful in achieving high-performance lead-free ceramics, paving the way for designing high-efficiency dielectric capacitors with a wide temperature range.

Bacterial infection of cutaneous wounds can easily lead to occurrence of chronic wounds and even more serious diseases. Therefore, multifunctional, biodegradable, and reusable wound dressings that can quickly manage wound infection and promote wound healing are urgently desired. Herein, inspired by the “capturing and killing” action of Drosera peltata Thunb., a biomimetic cellulose film was constructed to capture the bacteria (via the rough structure of the film) and kill them (via the combination of photodynamic therapy and chemotherapy) to promote wound tissue remodeling. The film (termed OBC-PR) was simply prepared by chemically crosslinking the oxidized bacterial cellulose (OBC) with polyhexamethylene guanidine hydrochloride (PHGH) and rose bengal (RB). Notably, it could effectively capture Escherichia coli and Staphylococcus aureus bacterial cells with capture efficiencies of ∼99 % and ∼96 %, respectively, within 10 min. Furthermore, the in vivo experiments showed that OBC-PR could effectively promote the macrophage polarization toward the M2 phenotype and adequately induce the reconstruction of blood vessels and nerves, thus promoting wound healing. This study provides a potential direction for designing multifunctional wound dressings for managing infected skin wounds in the future.

Abstract Background Hypertension (HT) is one of the most common manifestations in patients with catecholamine-secreting neuroendocrine tumors. Although the cardiovascular manifestations of these tumors have been described, there have been no large-scale investigations of the profile of HT and changes in cardiac structure and function that occur in patients with pheochromocytomas and paragangliomas (PPGL). Materials and methods In this study, we investigated the prevalence of HT and left ventricular remodeling (LVR) in a cohort of 598 patients who underwent surgery for PPGL at our center between January 2001 and April 2022. Information on demographics, reason for hospitalization, medical history, biochemical parameters, findings on echocardiography, and tumor characteristics were recorded. The LVR index was compared according to whether or not there was a history of HT. Results The average age was 47.07 ± 15.07 years, and 277 (46.32%) of the patients were male. A history of HT was found in 423 (70.74%) of the 598 patients. Paraganglioma was significantly more common in the group with HT (26.00% vs. 17.71%, P = 0.030) and significantly less likely to be found incidentally during a health check-up in this group (22.93% vs. 59.43%, P

Abstract Background and aims Electrophysiological characteristics and radiofrequency catheter ablation (RFCA) of premature ventricular contractions (PVCs) originating from the superior septal left ventricle (SSLV) have not yet been fully characterized. Methods and results This study included 247 patients who underwent RFCA for PVCs arising from the ventricular outflow tract between February 2020 and August 2022. The successful ablation site was on the SSLV in 37 of the 247 patients. In 12 (32.4%) of those 37 patients, a low amplitude and high frequency spiky potential (SP) was recognized. Five patients showed a narrow QRS duration (86.8 ± 4.6 ms), with a discrete SP observed in PVCs and sinus rhythm, which showed an isoelectric line with the ventricular electrogram at the earliest activation site. Seven patients showed a wide QRS duration (131.6 ± 4.5 ms), with SP observed in PVCs without an isoelectric line with the ventricular electrogram. RFCA was successful at the site of the earliest SP in all 12 patients. The time from SP onset at the successful ablation site to the QRS onset (local activation time) was 30 ± 12 ms, which differed significantly from that for the remaining 25 patients withoutSP(22.1 ± 7.1 ms, P

Abstract Bacteriophages (phages) represent a unique category of viruses with a remarkable ability to selectively infect host bacteria, characterized by their assembly from proteins and nucleic acids. Leveraging their exceptional biological properties and modifiable characteristics, phages emerge as innovative, safe, and efficient delivery vectors. The potential drawbacks associated with conventional nanocarriers in the realms of drug and gene delivery include a lack of cell-specific targeting, cytotoxicity, and diminished in vivo transfection efficiency. In contrast, engineered phages, when employed as cargo delivery vectors, hold the promise to surmount these limitations and attain enhanced delivery efficacy. This review comprehensively outlines current strategies for the engineering of phages, delineates the principal types of phages utilized as nanocarriers in drug and gene delivery, and explores the application of phage-based delivery systems in disease therapy. Additionally, an incisive analysis is provided, critically examining the challenges confronted by phage-based delivery systems within the domain of nanotechnology. The primary objective of this article is to furnish a theoretical reference that contributes to the reasoned design and development of potent phage-based delivery systems. Graphical abstract

Abstract Steering on the intrinsic active site of an electrode material is essential for efficient electrochemical biomass upgrading to valuable chemicals with high selectivity. Herein, we show that an in-situ surface reconstruction of a two-dimensional layered CdPS 3 nanosheet electrocatalyst, triggered by electrolyte, facilitates efficient 5-hydroxymethylfurfural (HMF) hydrogenation to 2,5-bis(hydroxymethyl)furan (BHMF) under ambient condition. The in-situ Raman spectroscopy and comprehensive post-mortem catalyst characterizations evidence the construction of a surface-bounded CdS layer on CdPS3 to form CdPS 3 /CdS heterostructure. This electrocatalyst demonstrates promising catalytic activity, achieving a Faradaic efficiency for BHMF reaching 91.3 ± 2.3 % and a yield of 4.96 ± 0.16 mg/h at − 0.7 V versus reversible hydrogen electrode. Density functional theory calculations reveal that the in-situ generated CdPS 3 /CdS interface plays a pivotal role in optimizing the adsorption of HMF* and H* intermediate, thus facilitating the HMF hydrogenation process. Furthermore, the reconstructed CdPS 3 /CdS heterostructure cathode, when coupled with MnCo 2 O 4.5 anode, enables simultaneous BHMF and formate synthesis from HMF and glycerol substrates with high efficiency.

Abstract Background The prevalence of hyperuricaemia (HUA), a metabolic disorder characterized by elevated levels of uric acid, is on the rise and is frequently associated with renal injury. Gut microbiota and gut-derived uremic toxins are critical mediators in the gut-kidney axis that can cause damage to kidney function. Gut dysbiosis has been implicated in various kidney diseases. However, the role and underlying mechanism of the gut microbiota in HUA-induced renal injury remain unknown. Results A HUA rat model was first established by knocking out the uricase (UOX). HUA rats exhibited apparent renal dysfunction, renal tubular injury, fibrosis, NLRP3 inflammasome activation, and impaired intestinal barrier functions. Analysis of 16S rRNA sequencing and functional prediction data revealed an abnormal gut microbiota profile and activation of pathways associated with uremic toxin production. A metabolomic analysis showed evident accumulation of gut-derived uremic toxins in the kidneys of HUA rats. Furthermore, faecal microbiota transplantation (FMT) was performed to confirm the effects of HUA-induced gut dysbiosis on renal injury. Mice recolonized with HUA microbiota exhibited severe renal injury and impaired intestinal barrier functions following renal ischemia/reperfusion (I/R) surgery. Notably, in NLRP3-knockout (NLRP3−/−) I/R mice, the deleterious effects of the HUA microbiota on renal injury and the intestinal barrier were eliminated. Conclusion Our results demonstrate that HUA-induced gut dysbiosis contributes to the development of renal injury, possibly by promoting the production of gut-derived uremic toxins and subsequently activating the NLRP3 inflammasome. Our data suggest a potential therapeutic strategy for the treatment of renal diseases by targeting the gut microbiota and the NLRP3 inflammasome. Video Abstract Graphical Abstract

Abstract Background Intra-operative anaesthesia management should be optimised to reduce the occurrence of postoperative nausea and vomiting in high-risk patients; however, a single intervention may not effectively reduce postoperative nausea and vomiting in such patients. This study assessed the effect of an optimised anaesthetic protocol versus a conventional one on postoperative nausea and vomiting in patients who underwent laparoscopic sleeve gastrectomy. Methods A single-centre randomised trial was conducted at Peking University Shenzhen Hospital from June 2021 to December 2022. Among 168 patients who underwent laparoscopic sleeve gastrectomy, 116 qualified, and 103 completed the study with available data. Patients were categorized into the conventional group (received sevoflurane and standard fluids) and the optimised group (underwent propofol-based anaesthesia and was administered goal-directed fluids). The primary endpoints were postoperative nausea and vomiting incidence and severity within 24 h. Results Postoperative nausea and vomiting assessment at 0–3 h post-surgery revealed no significant differences between groups. However, at 3–24 h, the optimised anaesthetic protocol group showed lower postoperative nausea and vomiting incidence and severity than those of the conventional group (P = 0.005). In the conventional group, 20 (37.04%) patients experienced moderate-to-severe postoperative nausea and vomiting, compared to six (12.25%) patients in the optimised group (odds ratio = 0.237; 95% CI = 0.086, 0.656; P = 0.006). No significant differences were noted in antiemetic treatment, moderate-to-severe pain incidence, anaesthesia recovery, post-anaesthetic care unit stay, or postoperative duration between the groups. While the total intra-operative infusion volumes were comparable, the optimised group had a significantly higher colloidal infusion volume (500 mL vs. 0 mL, P = 0.014) than that of the conventional group. Conclusions The incidence and severity of postoperative nausea and vomiting 3–24 h postoperatively in patients who underwent laparoscopic sleeve gastrectomy were significantly lower with propofol-based total intravenous anaesthesia and goal-directed fluid therapy than with sevoflurane anaesthesia and traditional fluid management. Total intravenous anaesthesia is an effective multimodal antiemetic strategy for bariatric surgery. Trial registration This trial was registered with the Chinese Clinical Trial Registry (ChiCTR-TRC- 2,100,046,534, registration date: 21 May 2021).

Glutamine, one of the most abundant amino acids in the body, has been shown to exert various beneficial effects in pigs. However, knowledge regarding the role of dietary glutamine in low-protein diet-fed piglets remains scarce. The present study aimed to investigate the effects of different levels of L-glutamine on growth performance, serum biochemistry parameters, redox status, amino acids, and fecal microbiota in low-protein diet-fed piglets. A total of 128 healthy crossbred piglets (Landrace × Yorkshire) were randomly allocated into 4 groups of 4 replicate pens, with 8 piglets per pen. Piglets in the 4 groups were fed with corn and soybean meal-based low-protein diets (crude protein level, 17%) that contained 0%, 1%, 2%, and 3% L-glutamine, respectively, for 28 d. Pigs administered 1% L-glutamine had greater body weight on d 28 and average daily gain (ADG, P

The recycling of graphite from spent lithium-ion batteries (LIBs) is overlooked due to its relatively low added value and the lack of efficient recovering methods. To reuse the spent graphite anodes, we need to eliminate their useless components (mainly the degraded solid electrolyte interphase, SEI) and reconstruct their damaged structure. Herein, a facile and efficient strategy is proposed to recycle the spent graphite on the basis of the careful investigation of the composition of the cycled graphite anodes and the rational design of the regeneration processes. The regenerated graphite, which is revitalized by calcination treatment and acid leaching, delivers superb rate performance and a high specific capacity of 370 mAh g−1 (∼99% of its theoretical capacity) after 100 cycles at 0.1 C, superior to the commercial graphite anodes. The improved electrochemical performance could be attributed to unchoked Li+ transport channels and enhanced charge transfer reaction due to the effective destruction of the degraded SEI and the full recovery of the damaged structure of the spent graphite. This work clarifies that the electrochemical performance of the regenerated graphite could be deteriorated by even a trace amount of the residual “impurity” and provides a facile method for the efficient regeneration of graphite anodes.

The leading design for plasma-facing high heat flux components in proposed fusion reactors involves joining plasma-facing tungsten tiles to underlying reduced activation ferritic-martensitic (RAFM) steel structures. Due to significant differences in the physical properties between W and steel, an effective method for joining them while preserving the mechanical and microstructural properties under service thermo-mechanical load is yet to be demonstrated. A transitional multilayer consisting of three layers (VCrTi, VCrAl, and FeCrAl) between W and steel is designed with the help of thermodynamic simulation and diffusion kinetics in an attempt to form solid solution bonding without forming brittle intermetallic phases. The solid solution bonding is desirable to mitigate the drastically different thermal expansion between W and steels. The multilayer structure was fabricated using spark plasma sintering (SPS). The microstructure of the bonded transition layers was analyzed after long-term annealing at 620 °C up to 1000h, through scanning electron microscope, energy dispersive spectroscopy and electron backscattering diffraction. Interdiffusion kinetics between layers and reliability of mobility database were also analyzed. This work provides a good understanding of thermal stability as well as the efficacy of multilayer functionally graded transition layer for joining W to ferritic/martensitic steel.

Background and objective Targeted therapies are ineffective in lung squamous cancer (LUSC), and the low response rate of immunotherapy hampers its application in LUSC, so it is urgent to explore new strategies for LUSC treatment. Ferroptosis plays an important role in tumour suppression. The aim of this study was to investigate the role and mechanism of targeting 3-hydroxy-3-methylglutaryl-CoA synthase 1 (HMGCS1) in regulating ferroptosis in LUSC cells, in order to provide a new research direction for LUSC therapy. Methods The expression of HMGCS1 in LUSC was analysed by The Cancer Genome Atlas (TCGA) and Clinical Proteomic Tumor Analysis Consortium (CPTAC) online databases; the relationship between HMGCS1 and survival time of lung cancer was analysed by the Kaplan-Meier Plotter online survival database; the expression level of HMGCS1 in LUSC tissues was verified by immunohistochemistry. After interfering with HMGCS1 expression by small interfering RNA (siRNA), cell activity and cell migration ability were detected by CCK8 and Transwell assay; apoptosis was detected by flow cytometry after interfering with HMGCS1 or after treatment with the HMGCS1 inhibitor of hymeglusin; Fe2+, reactive oxygen species (ROS) and lipid peroxidation levels were detected by flow cytometry and high-content confocal fluorescence imaging systems, respectively in SKMES cells after inhibition of HMGCS1; and Western blot was performed to detect the expression of ACSL4, GPX4 and SLC7A11, which are markers of the ferroptosis pathway after inhibition of HMGCS1. Results HMGCS1 mRNA and protein levels were significantly high in LUSC; siRNA interference with HMGCS1 expression inhibited the proliferative activity and migration ability of LUSC cells, but had no significant effect on apoptosis. Interference with HMGCS1 or treatment with the HMGCS1 inhibitor of hymeglusin significantly promoted intracellular Fe2+, ROS and lipid peroxidation levels in SKMES cells, and induced ferroptosis in LUSC cells; Western blot assay showed that inhibition of HMGCS1 significantly promoted the expression of ACSL4. Conclusion Inhibition of HMGCS1, a target of LUSC, promotes ferroptosis in lung cancer cells and provides a research basis for screening new therapeutic targets for LUSC.

Abstract Accumulating evidence indicates that exosomal proteins are critical in diagnosing malignant tumors. To identify novel exosomal biomarkers for lung cancer diagnosis, we isolated plasma exosomes from 517 lung cancer patients and 168 healthy controls (NLs)—186 lung adenocarcinoma (LUAD) patients (screening (SN): 20, validation (VD): 166), 159 lung squamous carcinoma (LUSC) patients (SN: 20, VD: 139), 172 benign nodules (LUBN) patients (SN: 20, VD: 152) and 168 NLs (SN: 20, VD: 148)—and randomly assigned them to the SN or VD group. Proteomic analysis by LC–MS/MS and PRM were performed on all groups. The candidate humoral markers were evaluated and screened by a machine learning method. All selected biomarkers were identified in the VD groups. For LUAD, a 7-protein panel had AUCs of 97.9% and 87.6% in the training and test sets, respectively, and 89.5% for early LUAD. For LUSC, an 8-protein panel showed AUCs of 99.1% and 87.0% in the training and test sets and 92.3% for early LUSC. For LUAD + LUSC (LC), an 8-protein panel showed AUCs of 85.9% and 80.3% in the training and test sets and 87.1% for early LC diagnosis. The characteristics of the exosomal proteome make exosomes potential diagnostic tools.

Abstract We present the Manatee variational autoencoder model to predict transcription factor (TF) perturbation-induced transcriptomes. We demonstrate that the Manatee in silico perturbation analysis recapitulates target transcriptomic phenotypes in diverse cellular lineage transitions. We further propose the Manatee in silico screening analysis for prioritizing TF combinations targeting desired transcriptomic phenotypes.

Abstract Background A growing body of research suggests that heat shock proteins (HSPs) may serve as diagnostic biomarkers for hepatocellular carcinoma (HCC), but their results are still controversial. This meta-analysis endeavors to evaluate the diagnostic accuracy of HSPs both independently and in conjunction with alpha-fetoprotein (AFP) as novel biomarkers for HCC detection. Methods Pooled statistical indices, including sensitivity, specificity, diagnostic odds ratio (DOR), positive likelihood ratio (PLR), and negative likelihood ratio (NLR) with 95% confidence intervals (CI), were computed to assess the diagnostic accuracy of HSPs, AFP, and their combinations. Additionally, the area under the summary receiver operating characteristic (SROC) curve (AUC) was determined. Results A total of 2013 HCC patients and 1031 control subjects from nine studies were included in this meta-analysis. The summary estimates for HSPs and AFP are as follows: sensitivity of 0.78 (95% CI: 0.69–0.85) compared to 0.73 (95% CI: 0.65–0.80); specificity of 0.89 (95% CI: 0.81–0.95) compared to 0.86 (95% CI: 0.77–0.91); PLR of 7.4 (95% CI: 3.7–14.9) compared to 5.1 (95% CI: 3.3–8.1); NLR of 0.24 (95% CI: 0.16–0.37) compared to 0.31 (95% CI: 0.24–0.41); DOR of 30.19 (95% CI: 10.68–85.37) compared to 16.34 (95% CI: 9.69–27.56); and AUC of 0.90 (95% CI: 0.87–0.92) compared to 0.85 (95% CI: 0.82–0.88). The pooled sensitivity, specificity, PLR, NLR, DOR and AUC were 0.90 (95% CI: 0.82–0.95), 0.94 (95% CI: 0.82–0.98), 14.5 (95% CI: 4.6–45.4), 0.11 (95% CI: 0.06–0.20), 133.34 (95% CI: 29.65–599.61), and 0.96 (95% CI: 0.94–0.98) for the combination of HSPs and AFP. Conclusion Our analysis suggests that HSPs have potential as a biomarker for clinical use in the diagnosis of HCC, and the concurrent utilization of HSPs and AFP shows notable diagnostic effectiveness for HCC.

Abstract Background Numerous studies have been conducted to investigate the relationship between ABO and Rhesus (Rh) blood groups and various health outcomes. However, a comprehensive evaluation of the robustness of these associations is still lacking. Methods We searched PubMed, Web of Science, Embase, Scopus, Cochrane, and several regional databases from their inception until Feb 16, 2024, with the aim of identifying systematic reviews with meta-analyses of observational studies exploring associations between ABO and Rh blood groups and diverse health outcomes. For each association, we calculated the summary effect sizes, corresponding 95% confidence intervals, 95% prediction interval, heterogeneity, small-study effect, and evaluation of excess significance bias. The evidence was evaluated on a grading scale that ranged from convincing (Class I) to weak (Class IV). We assessed the certainty of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation criteria (GRADE). We also evaluated the methodological quality of included studies using the A Measurement Tool to Assess Systematic Reviews (AMSTAR). AMSTAR contains 11 items, which were scored as high (8–11), moderate (4–7), and low (0–3) quality. We have gotten the registration for protocol on the PROSPERO database (CRD42023409547). Results The current umbrella review included 51 systematic reviews with meta-analysis articles with 270 associations. We re-calculated each association and found only one convincing evidence (Class I) for an association between blood group B and type 2 diabetes mellitus risk compared with the non-B blood group. It had a summary odds ratio of 1.28 (95% confidence interval: 1.17, 1.40), was supported by 6870 cases with small heterogeneity (I 2 = 13%) and 95% prediction intervals excluding the null value, and without hints of small-study effects (P for Egger’s test > 0.10, but the largest study effect was not more conservative than the summary effect size) or excess of significance (P

Abstract Background Lung adenocarcinoma (LUAD) is a non-small cell carcinoma. Ribonuclease/angiogenin inhibitor 1 (RNH1) exerts multiple roles in virous cancers. E2F1 is a critical transcription factor involved in the LUAD development. Here, we analyze the expression of RNH1 in LUAD patients, investigate the biological function of RNH1 in LUAD, and demonstrate its potential mechanisms through E2F1 in LUAD. Methods In the present study, we presented the expression of RNH1 in LUAD based on the database and confirmed it by western blot detection of RNH1 in human LUAD tissues. Lentiviral infection was constructed to silence or overexpress RNH1 in NCI-H1395 and NCI-H1437 cells. We assess the role of RNH1 on proliferation in LUAD cells by MTT assay, colony formation assays, and cell cycle detection. Hoechst staining and flow cytometry were used to evaluate the effects of RNH1 on apoptosis of LUAD cells. The function of RNH1 in invasion and migration was investigated by Transwell assay. Dual luciferase assay, ChIP detection, and pull-down assay were conducted to explore the association of E2F1 in the maintenance of RNH1 expression and function. The regulation of E2F1 on the functions of RNH1 in LUAD cells was explored. Mouse experiments were performed to confirm the in-vivo role of RNH1 in LUAD. mRNA sequencing indicated that RNH1 overexpression altered the expression profile of LUAD cells. Results RNH1 expression in LUAD tissues of patients was presented in this work. Importantly, RNH1 knockdown improved the proliferation, migration and invasion abilities of cells and RNH1 overexpression produced the opposite effects. Dual luciferase assay proved that E2F1 bound to the RNH1 promoter (-1064 ∼ -1054, -1514 ∼ -1504) to reduce the transcriptional activity of RNH1. ChIP assay indicated that E2F1 DNA was enriched at the RNH1 promoter (-1148 ∼ -943, -1628 ∼ -1423). Pull-down assays also showed the association between E2F1 and RNH1 promoter (-1148 ∼ -943). E2F1 overexpression contributed to the malignant behavior of LUAD cells, while RNH1 overexpression reversed it. High-throughput sequencing showed that RNH1 overexpression induced multiple genes expression changes, thereby modulating LUAD-related processes. Conclusion Our study demonstrates that binding of E2F1 to the RNH1 promoter may lead to inhibition of RNH1 expression and thus promoting the development of LUAD.

Abstract Esophageal cancer is a common type of cancer that poses a significant threat to human health. While the pro-inflammatory cytokine IL-1β has been known to contribute to the development of various types of tumors, its role in regulating esophageal cancer progression has not been extensively studied. Our studies found that the expression of IL-1β and FOXO3A was increased in esophageal squamous cell carcinoma (ESCC). IL-1β not only increased the proliferation, migration, and invasion of two ESCC cell lines but also promoted tumor growth and metastasis in nude mice. We also observed that IL-1β and FOXO3A regulated the process of epithelial-mesenchymal transition (EMT) and autophagy. The PI3K/AKT pathway was found to be involved in the changes of FOXO3A with the expression level of IL-1β. The AKT agonist (SC79) reversed the reduction of FOXO3A expression caused by the knockdown of IL-1β, indicating that IL-1β plays a role through the PI3K/AKT/FOXO3A pathway. Furthermore, the knockdown of FOXO3A inhibited ESCC development and attenuated the pro-cancer effect of overexpressed IL-1β. Targeting IL-1β and FOXO3A may be potentially valuable for the diagnosis and treatment of ESCC.

Abstract Background Drug resistance poses a significant challenge in cancer treatment, particularly as a leading cause of therapy failure. Cisplatin, the primary drug for lung adenocarcinoma (LUAD) chemotherapy, shows effective treatment outcomes. However, the development of resistance against cisplatin is a major obstacle. Therefore, identifying genes resistant to cisplatin and adopting personalized treatment could significantly improve patient outcomes. Methods By examining transcriptome data of cisplatin-resistant LUAD cells from the GEO database, 181 genes associated with cisplatin resistance were identified. Using univariate regression analysis, random forest and multivariate regression analyses, two prognostic genes, E2F7 and FAM83A, were identified. This study developed a prognostic model utilizing E2F7 and FAM83A as key indicators. The Cell Counting Kit 8 assay, Transwell assay, and flow cytometry were used to detect the effects of E2F7 on the proliferation, migration, invasiveness and apoptosis of A549/PC9 cells. Western blotting was used to determine the effect of E2F7 on AKT/mTOR signaling pathway. Results This study has pinpointed two crucial genes associated with cisplatin resistance, E2F7 and FAM83A, and developed a comprehensive model to assist in the diagnosis, prognosis, and evaluation of relapse risk in LUAD. Analysis revealed that patients at higher risk, according to these genetic markers, had elevated levels of immune checkpoints (PD-L1 and PD-L2). The prognostic and diagnosis values of E2F7 and FAM83A were further confirmed in clinical data. Furthermore, inhibiting E2F7 in lung cancer cells markedly reduced their proliferation, migration, invasion, and increased apoptosis. In vivo experiments corroborated these findings, showing reduced tumor growth and lung metastasis upon E2F7 suppression in lung cancer models. Conclusion Our study affirms the prognostic value of a model based on two DEGs, offering a reliable method for predicting the success of tumor immunotherapy in patients with LUAD. The diagnostic and predictive model based on these genes demonstrates excellent performance. In vitro, reducing E2F7 levels shows antitumor effects by blocking LUAD growth and progression. Further investigation into the molecular mechanisms has highlighted E2F7’s effect on the AKT/mTOR signaling pathway, underscoring its therapeutic potential. In the era of personalized medicine, this DEG-based model promises to guide clinical practice.

Abstract The aims of our study were to examine whether initial or subsequent adiposity status had a greater effect on hypertension. We collected data in 1992 and again in 2007 from the same group of 597 individuals in the middle age. The subjects were classified into four groups: individuals with a normal body mass index (BMI) in 1992 and 2007 were in Group I; those with a normal BMI in 1992, but became overweight or obese in 2007 were in Group II; those who were overweight or obese in 1992, but had a normal BMI in 2007 were in Group III; and those who were overweight or obese in 1992 and 2007 were in Group IV. Their demographic data were recorded. The relationship between adiposity status and hypertension was analyzed using logistic regression model. The cumulative incidence of hypertension was 35.5%, 56.3%, 50.0%, and 65.1% for Group I to IV, respectively. Compared with Group I, after adjusted factors, the hazard ratio (HR) was 1.80 for Group II (P = .001), 1.40 for Group III (P = .150), and 2.31 for Group IV (P

Abstract Shale reservoirs have complex mineral compositions and are rich in micro-scale pores. It is of great scientific and engineering significance to explore the mechanism of external fluids on the pore throat structure of shale. In this paper, pure carbonaceous shale is taken as the research object, and the mechanism of the influence of slip water and reflux fluid on the pore throat structure is analyzed by using nuclear magnetic resonance (NMR) technology. Then, the sensitivity of different types of shale to external fluids is comparatively analyzed and summarized. The results show that (1) the oil slick has a certain effect on the total porosity of different types of shale. The rate of change is shown as carbonaceous shale (− 7.1%) > pure shale (− 1.6%). (b) For slickwater, the average reduction of macro- and micro/nanopores in carbonaceous shale is 90.0% and 5.0%, respectively, while the average reduction of macro- and mesopores in pure shale is 17.7% and 6.8%, respectively. (c) Total porosity of different shale types is insensitive to refluxing fluids. The average increase in macro-, meso-, and small pores of carbonaceous shale is 31.8%, 23.6%, and 20.2%, respectively; the average increase in macro- and small pores of pure shale is 17.1%.

Abstract Objectives This study aimed to evaluate the prognostic significance of postoperative Creatine Kinase type M and B (CK-MB) to total Creatine Kinase (CK) ratio (CK-MB/CK) in colorectal cancer (CRC) patients after radical resection. Methods This was a single-center retrospective cohort analysis. Subjects were stage I-III CRC patients hospitalized in Sichuan Cancer Hospital from January 2017 to May 2021. Patients were divided into abnormal group and normal group according to whether the CK-MB/CK ratio was abnormal after surgery. Through a comparative analysis of clinical data, laboratory test results, and prognosis differences between the two groups, we aimed to uncover the potential relationship between abnormal CK-MB > CK results and CRC patients. To gauge the impact of CK-MB/CK on overall survival (OS) and disease-free survival (DFS), we employed the multivariable COX regression and LASSO regression analysis. Additionally, Spearman correlation analysis, logistic regression, and receiver-operating characteristic (ROC) curve analysis were conducted to assess the predictive value of the CK-MB/CK ratio for postoperative liver metastasis. Results Cox regression analysis revealed that the CK-MB/CK ratio was a stable risk factors for OS (HR = 3.82, p

Abstract Impaired brain glucose metabolism is an early indicator of Alzheimer’s disease (AD); however, the fundamental mechanism is unknown. In this study, we found a substantial decline in isocitrate dehydrogenase 3β (IDH3β) levels, a critical tricarboxylic acid cycle enzyme, in AD patients and AD-transgenic mice’s brains. Further investigations demonstrated that the knockdown of IDH3β induced oxidation-phosphorylation uncoupling, leading to reduced energy metabolism and lactate accumulation. The resulting increased lactate, a source of lactyl, was found to promote histone lactylation, thereby enhancing the expression of paired-box gene 6 (PAX6). As an inhibitory transcription factor of IDH3β, the elevated PAX6 in turn inhibited the expression of IDH3β, leading to tau hyperphosphorylation, synapse impairment, and learning and memory deficits resembling those seen in AD. In AD-transgenic mice, upregulating IDH3β and downregulating PAX6 were found to improve cognitive functioning and reverse AD-like pathologies. Collectively, our data suggest that impaired oxidative phosphorylation accelerates AD progression via a positive feedback inhibition loop of IDH3β-lactate-PAX6-IDH3β. Breaking this loop by upregulating IDH3β or downregulating PAX6 attenuates AD neurodegeneration and cognitive impairments.

Abstract Induced resistance is considered an eco-friendly disease control strategy, which can enhance plant disease resistance by inducing the plant’s immune system to activate the defense response. In recent years, studies have shown that lactic acid can play a role in plant defense against biological stress; however, whether lactic acid can improve tobacco resistance to Phytophthora nicotianae, and its molecular mechanism remains unclear. In our study, the mycelial growth and sporangium production of P. nicotianae were inhibited by lactic acid in vitro in a dose-dependent manner. Application of lactic acid could reduce the disease index, and the contents of total phenol, salicylic acid (SA), jasmonic acid (JA), lignin and H2O2, catalase (CAT) and phenylalanine ammonia–lyase (PAL) activities were significantly increased. To explore this lactic acid-induced protective mechanism for tobacco disease resistance, RNA-Seq analysis was used. Lactic acid enhances tobacco disease resistance by activating Ca2+, reactive oxygen species (ROS) signal transduction, regulating antioxidant enzymes, SA, JA, abscisic acid (ABA) and indole-3-acetic acid (IAA) signaling pathways, and up-regulating flavonoid biosynthesis-related genes. This study demonstrated that lactic acid might play a role in inducing resistance to tobacco black shank disease; the mechanism by which lactic acid induces disease resistance includes direct antifungal activity and inducing the host to produce direct and primed defenses. In conclusion, this study provided a theoretical basis for lactic acid-induced resistance and a new perspective for preventing and treating tobacco black shank disease.

Abstract Objectives Ovarian cancer (OC) can occur at different ages and is affected by a variety of factors. In order to evaluate the risk of cardiovascular mortality in patients with ovarian cancer, we included influencing factors including age, histological type, surgical method, chemotherapy, whether distant metastasis, race and developed a nomogram to evaluate the ability to predict occurrence. At present, we have not found any correlation studies on cardiovascular death events in patients with ovarian cancer. This study was designed to provide targeted measures for effective prevention of cardiovascular death in patients with ovarian cancer. Methods Kaplan–Meier analysis and multivariable Cox proportional model were performed to evaluate the effectiveness of cardiovascular diseases on overall survival (OS) and ovarian cancer‐specific survival (OCSS). We compared multiple groups including clinical, demographic, therapeutic characteristics and histological types. Cox risk regression analysis, Kaplan–Meier survival curves, and propensity score matching were employed for analyzing the data. Results A total of 88,653 ovarian cancer patients were collected, of which 2,282 (2.57%) patients died due to cardiovascular-related diseases. Age, chemotherapy and whether satisfactory cytoreduction surgery is still the most important factors affecting the prognosis of ovarian cancer patients, while different histological types, diagnosis time, and race also have a certain impact on the prognosis. The newly developed nomogram model showed excellent predictive performance, with a C-index of 0.759 (95%CI: 0.757–0.761) for the group. Elderly patients with ovarian cancer are still a high-risk group for cardiovascular death [HR: 21.07 (95%CI: 5.21–85.30), p

Lung cancer is a leading cause of cancer death worldwide, with high incidence and poor survival rates. Cold atmospheric plasma (CAP) technology has emerged as a promising therapeutic approach for cancer treatment, inducing oxidative stress in malignant tissues without causing thermal damage. However, the role of CAP in regulating lung cancer cell ferroptosis remains unclear. Here, we observed that CAP effectively suppressed the growth and migration abilities of lung cancer cells, with significantly increased ferroptotic cell death, lipid peroxidation, and decreased mitochondrial membrane potential. Mechanistically, CAP regulates SLC7A11-mediated cell ferroptosis by modulating HOXB9. SLC7A11, a potent ferroptosis suppressor, was markedly reduced by HOXB9 knockdown, while it was enhanced by overexpressing HOXB9. The luciferase and ChIP assays confirmed that HOXB9 can directly target SLC7A11 and regulate its gene transcription. Additionally, CAP enhanced the acetylation modification level of HOXB9 by promoting its interaction with acetyltransferase p300/CBP-associated factor (PCAF). Acetylated HOXB9 affects its protein ubiquitination modification level, which in turn affects its protein stability. Notably, the upregulation of SLC7A11 and HOXB9 mitigated the suppressive effects of CAP on ferroptosis status, cell proliferation, invasion, and migration in lung cancer cells. Furthermore, animal models have also confirmed that CAP can inhibit the progression of lung cancer in vivo. Overall, this study highlights the significance of the downregulation of the HOXB9/SLC7A11 axis by CAP treatment in inhibiting lung cancer, offering novel insights into the potential mechanisms and therapeutic strategies of CAP for lung cancer.

Background Neoadjuvant chemoimmunotherapy has a promising effect on locally advanced esophageal squamous cell carcinoma (ESCC). However, reliable biomarkers robustly predicting therapeutic response are still lacking.Methods Formalin-fixed and paraffin-embedded pre-neoadjuvant chemoimmunotherapy biopsy samples from locally advanced ESCC patients were collected. Cohort 1 composed of 66 locally advanced ESCC patients from a prospective clinical trial (NCT04506138) received two cycles of camrelizumab in combination with nab-paclitaxel and carboplatin every 3 weeks. Cohort 2 included 48 patients receiving various types of immune checkpoint inhibitors with (nab-)paclitaxel and platinum-based chemotherapy as neoadjuvant therapy. Cohort 3 consisted of 27 ESCC patients receiving neoadjuvant treatment of toripalimab with chemotherapy and was used as the external validation dataset. Targeted RNA sequencing, immunohistochemistry for programmed death ligand 1 (PD-L1), and multiplex immunofluorescence (mIF) imaging were performed.Results Integration of targeted RNA sequencing, PD-L1 immunohistochemistry, and mIF revealed a significant immune-suppressive microenvironment with higher neutrophil infiltration, enriched TGF-β, and cell cycle pathways in non-pathological complete response (non-pCR) patients. NK, activated CD4+ T cell infiltration, interferon-gamma, antigen processing and presentation, and other immune response signatures were significantly associated with pCR. Based on discovered tumor microenvironmental characteristics and their closely related genes were screened. Consequently, a seven-gene neoadjuvant chemoimmunotherapy risk prediction signature (NCIRPs) model, was constructed. In addition to cohort 1, this model alone or with PD-L1-combined positive score (CPS) demonstrated a higher prediction accuracy of pathological response than PD-L1 CPS or other routinely used immune signatures, such as IFN-γ, in cohorts 2 and 3. Neither prognostic association nor correlation with response to chemoradiotherapy was observed in The Cancer Genome Atlas Program ESCC dataset or in ESCC patients in the neoadjuvant chemoradiotherapy cohort (cohort 4).Conclusion The NCIRPs model that was developed and validated using treatment-naïve endoscopic samples from the largest ESCC neoadjuvant chemoimmunotherapy dataset represents a robust and clinically meaningful approach to select a putative responder for neoadjuvant chemoimmunotherapy in locally advanced ESCC patients.

Abstract Background Chronic obstructive pulmonary disease (COPD) contributes to the incidence and prognosis of lung cancer. The presence of COPD significantly increases the risk of lung squamous cell carcinoma (LSCC). COPD may promote an immunosuppressive microenvironment in LSCC by regulating the expression of immune‐inhibitory factors in T cells, although the mechanisms remain unclear. In this study, we aimed to decipher the tumour microenvironment signature for LSCC with COPD at a single‐cell level. Methods We performed single‐cell RNA sequencing on tumour tissues from LSCC with or without COPD, then investigated the features of the immune and tumour cells. We employed multiple techniques, including multispectral imaging, flow cytometry, tissue microarray analysis, survival analysis, co‐culture systems and in vitro and in vivo treatment experiments, to validate the findings obtained from single‐cell analyses. Results LSCC with COPD showed increased proportions of tumour‐associated macrophages (TAMs) and higher levels of CD8+ T cell exhaustion molecules, which contributed to an immunosuppressive microenvironment. Further analysis revealed a critical cluster of CD74+ tumour cells that expressed both epithelial and immune cell signatures, exhibited a stronger capacity for tumorigenesis and predicted worse overall survival. Notably, migration inhibitory factor (MIF) secreted by TAMs from LSCC with COPD may promote the activation of CD74. MIF‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐programmed cell death‐1 ligand 1 signalling pathway, facilitating tumour proliferation and immune evasion. Conclusions Our comprehensive picture of the tumour ecosystem in LSCC with COPD provides deeper insights into relevant immune evasion mechanisms and potential targets for immunotherapy. Highlight Our results demonstrated higher proportions of tumour‐associated macrophages (TAMs) and higher levels of exhaustion molecules in CD8+ T cells in the microenvironment of LSCC with COPD. CD74+tumour cells were associated with poor disease prognosis. Migration inhibitory factor (MIF)‐CD74 may interact with CD8+ T cells and impair their anti‐tumour activity by regulating the PI3K‐STAT3‐PD‐L1 signalling pathway, facilitating immune evasion.

Background: Cuproptosis, one of the most recently discovered forms of cell death, is induced by the disruption of copper binding to the mitochondrial respiratory acylation components. However, the mechanism underlying cuproptosis in uveal melanoma (UM) has not yet been adequately studied. Methods: RNA and clinical data were obtained from The Cancer Genome Atlas (TCGA) database. Differentially expressed cuproptosis-related genes were identified by R software. A prognostic signature was constructed by applying LASSO regression and Cox regression models. The associations between the signature and the immune microenvironment, overall survival, and drug sensitivity were studied. In addition, qPCR and Western blotting were performed on UM cells and RPE cell lines to verify the expression levels of the genes encoding dihydrolipoamide dehydrogenase (DLD) and dihydrolipoamide S-succinyltransferase (DLST) in UM cases. Results: Using a cuproptosis-related prognostic signature, UM samples were classified into high- and low-risk groups. A significant difference in overall survival between the two risk groups was evident. Receiver operating characteristic curves demonstrated that the signature is a reliable predictor of prognosis. Immune cell infiltration, drug sensitivity, and immune checkpoint expression were analysed. Significant immune difference between the two high-risk groups was found, and the high expression of immune checkpoints in high-risk groups suggests significant immunotherapy potential. In addition, drug sensitivity analysis experiments suggest that erlotinib may be a potential treatment for high-risk patients. The results of in vitro experiments confirmed that DLD and DLST had higher expression levels in UM cell lines. Conclusions: The prognostic signature developed in this study is a reliable biomarker for predicting the prognosis of UM and may serve as a tool for personalised treatment of patients with UM.