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Turbot (Scophthalmus maximus) is one of the most economically important fish in the northern coastal areas of China. Recently, low salinity stress is an important factor influencing the development of the turbot industry. Lately, the industry has faced challenges posed by low salinity stress, a key factor influencing turbot development. Salinity fluctuations represent a crucial environmental stressor in aquaculture, impacting osmotic pressure and inducing abnormal energy metabolism. Our preliminary research had identified that low salinity stress contributes to lipid metabolism disorders in turbot. This study aims to investigate the impact of varying lipid concentration levels on the lipid metabolism disorders induced by low salinity stress. To achieve this, feeding experiments were conducted with different lipid concentration levels under low salinity stress conditions, determining the optimal lipid requirement for turbot to cope with reduced salinity. Three salinity gradients (10, 20, and 30) were employed, with four lipid concentration gradients (8%, 12%, 16%, and 20%) for each salinity group. The results revealed that at a lipid concentration of 16%, no significant difference in the growth performance of juvenile turbot was observed between the salinities of 20 and 30. However, the growth performance under a salinity of 10 was lower than that under salinities of 20 and 30. Notably, under a salinity of 10, the growth performance of juvenile turbot increased with higher lipid concentrations, reaching its peak at 20%, surpassing values under the salinities of 20 and 30. Regarding the expression of genes related to lipid metabolism, under the salinities of 10 and 20, the expression levels of genes related to lipid synthesis, lxrα, cyp7a1, and srebp-1, showed a trend of first increasing and then decreasing with increasing lipid concentration, particularly under the salinity of 10. The expression level of the 12% lipid group was higher than that of other groups and the expression level of the 20% lipid group was significantly lower than that of other groups (P < 0.05). In addition, under a salinity of 10, the expression levels of acc and fas also showed a similar situation. They were both suppressed in the 20% lipid group, and the expression levels were higher in the 12% lipid group. The expression level of the gene apoa-IV related to lipid absorption in the 20% lipid group under a salinity of 10 was markedly higher than that in other groups under the same salinity conditions (P < 0.05) and it showed a change with salt under the condition of 20% lipid concentration. The increasing and decreasing trends were contrary to the trends in other lipid groups. The aforementioned results show that after low-salt stress affects lipid metabolism, feeds with different lipid concentrations can alleviate the adverse effects of the stress from the perspectives of lipid synthesis and lipid absorption, and this mitigation effect is more reflected at the level of lipid absorption, thereby improving growth performance under low salt stress. The results reveal the adaptability of fish to low salt from the perspective of salinity affecting lipid metabolism, enrich the concentration of fish stress physiology, and provide theoretical and technical support for the breeding of low-salt tolerant turbot varieties.

Abstract WNT signaling is fundamental in development and homeostasis, but how the Frizzled receptors (FZDs) propagate signaling remains enigmatic. Here, we present the cryo-EM structure of FZD4 engaged with the DEP domain of Dishevelled 2 (DVL2), a key WNT transducer. We uncover a distinct binding mode where the DEP finger-loop inserts into the FZD4 cavity to form a hydrophobic interface. FZD4 intracellular loop 2 (ICL2) additionally anchors the complex through polar contacts. Mutagenesis validates the structural observations. The DEP interface is highly conserved in FZDs, indicating a universal mechanism by which FZDs engage with DVLs. We further reveal that DEP mimics G-protein/β-arrestin/GRK to recognize an active conformation of receptor, expanding current GPCR engagement models. Finally, we identify a distinct FZD4 dimerization interface. Our findings delineate the molecular determinants governing FZD/DVL assembly and propagation of WNT signaling, providing long-sought answers underlying WNT signal transduction.

Abstract Background Pig organ xenotransplantation is a potential solution for the severe organ shortage in clinic, while immunogenic genes need to be eliminated to improve the immune compatibility between humans and pigs. Current knockout strategies are mainly aimed at the genes causing hyperacute immune rejection (HAR) that occurs in the first few hours while adaptive immune reactions orchestrated by CD4 T cell thereafter also cause graft failure, in which process the MHC II molecule plays critical roles. Methods Thus, we generate a 4‐gene (GGTA1, CMAH, β4GalNT2, and CIITA) knockout pig by CRISPR/Cas9 and somatic cell nuclear transfer to compromise HAR and CD4 T cell reactions simultaneously. Results We successfully obtained 4KO piglets with deficiency in all alleles of genes, and at cellular and tissue levels. Additionally, the safety of our animals after gene editing was verified by using whole‐genome sequencing and karyotyping. Piglets have survived for more than one year in the barrier, and also survived for more than 3 months in the conventional environment, suggesting that the piglets without MHC II can be raised in the barrier and then gradually mated in the conventional environment. Conclusions 4KO piglets have lower immunogenicity, are safe in genomic level, and are easier to breed than the model with both MHC I and II deletion.

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 Not all patients with glioblastoma multiforme (GBM) eligible for systemic chemotherapy after upfront surgery and radiotherapy finally receive it. The information on patients with GBM was retrieved from the surveillance, epidemiology, and end results database. Patients who underwent upfront surgery or biopsy and external beam radiotherapy between 2010 and 2019 were eligible for systemic chemotherapy. The available patient and tumor characteristics were assessed using multivariable logistic regression and chi-squared test. Out of the 16,682 patients eligible, 92.1% underwent systemic chemotherapy. The characteristics linked to the lowest systemic chemotherapy utilization included tumors of the brain stem/cerebellum (P = 0.01), former years of diagnosis (P = 0.001), ≥ 80 years of age (P

Abstract Background Heart failure is a disease that threatens global public safety. In recent years, the obesity paradox has been studied in cardiovascular disease and other fields. With the progress of aging, metabolic changes and regulation of fat function, it also provides many bridges for the dialogue between disease and molecular metabolism. The purpose of this study is to investigate the effect of obesity on the outcome of adult intensive care patients with heart failure combined with age factors. Method Data were derived from the fourth-generation Medical Information Marketplace for Intensive Care (MIMIC-IV version2.1) using structured query language on the Navicat (12.0.11) platform. People were divided into two groups based on the body mass index (BMI), one group with BMI ≥ 30 kg/m² and another group with BMI

Images and videos provide a wealth of information for people in production and life. Although most digital information is transmitted via optical fiber, the image acquisition and transmission processes still rely heavily on electronic circuits. The development of all-optical transmission networks and optical computing frameworks has pointed to the direction for the next generation of data transmission and information processing. Here, we propose a high-speed, low-cost, multiplexed parallel and one-piece all-fiber architecture for image acquisition, encoding, and transmission, called the Multicore Fiber Acquisition and Transmission Image System (MFAT). Based on different spatial and modal channels of the multicore fiber, fiber-coupled self-encoding, and digital aperture decoding technology, scenes can be observed directly from up to 1 km away. The expansion of capacity provides the possibility of parallel coded transmission of multimodal high-quality data. MFAT requires no additional signal transmitting and receiving equipment. The all-fiber processing saves the time traditionally spent on signal conversion and image pre-processing (compression, encoding, and modulation). Additionally, it provides an effective solution for 2D information acquisition and transmission tasks in extreme environments such as high temperatures and electromagnetic interference.

Abstract Background Properly understanding the origin and progression of the thoracic aortic aneurysm (TAA) can help prevent its growth and rupture. For a better understanding of this pathogenesis, the aortic blood flow has to be studied and interpreted in great detail. We can obtain detailed aortic blood flow information using magnetic resonance imaging (MRI) based computational fluid dynamics (CFD) with a prescribed motion of the aortic wall. Methods We performed two different types of simulations—static (rigid wall) and dynamic (moving wall) for healthy control and a patient with a TAA. For the latter, we have developed a novel morphing approach based on the radial basis function (RBF) interpolation of the segmented 4D-flow MRI geometries at different time instants. Additionally, we have applied reconstructed 4D-flow MRI velocity profiles at the inlet with an automatic registration protocol. Results The simulated RBF-based movement of the aorta matched well with the original 4D-flow MRI geometries. The wall movement was most dominant in the ascending aorta, accompanied by the highest variation of the blood flow patterns. The resulting data indicated significant differences between the dynamic and static simulations, with a relative difference for the patient of 7.47±14.18% in time-averaged wall shear stress and 15.97±43.32% in the oscillatory shear index (for the whole domain). Conclusions In conclusion, the RBF-based morphing approach proved to be numerically accurate and computationally efficient in capturing complex kinematics of the aorta, as validated by 4D-flow MRI. We recommend this approach for future use in MRI-based CFD simulations in broad population studies. Performing these would bring a better understanding of the onset and growth of TAA.

Abstract Background Asthma’s complexity, marked by airway inflammation and remodeling, is influenced by hypoxic conditions. This study focuses on the role of Hypoxia-Inducible Factor-1 Alpha (HIF-1α) and P53 ubiquitination in asthma exacerbation. Methods High-throughput sequencing and bioinformatics were used to identify genes associated with asthma progression, with an emphasis on GO and KEGG pathway analyses. An asthma mouse model was developed, and airway smooth muscle cells (ASMCs) were isolated to create an in vitro hypoxia model. Cell viability, proliferation, migration, and apoptosis were assessed, along with ELISA and Hematoxylin and Eosin (H&E) staining. Results A notable increase in HIF-1α was observed in both in vivo and in vitro asthma models. HIF-1α upregulation enhanced ASMCs’ viability, proliferation, and migration, while reducing apoptosis, primarily via the promotion of P53 ubiquitination through MDM2. In vivo studies showed increased inflammatory cell infiltration and airway structural changes, which were mitigated by the inhibitor IDF-11,774. Conclusion The study highlights the critical role of the HIF-1α-MDM2-P53 axis in asthma, suggesting its potential as a target for therapeutic interventions. The findings indicate that modulating this pathway could offer new avenues for treating the complex respiratory disorder of asthma.

Abstract Background Cardiac arrest after coronary artery bypass grafting (CABG) is a serious complication with low survival rate. The prognosis of patients with cardiac arrest in the general ward is worse than that in the intensive care unit (ICU) because of the delayed and poor rescue conditions. Methods This retrospective study included patients who experienced cardiac arrest after CABG surgery between January 2010 and December 2019 at the Fuwai Hospital. Differences in cardiac arrest between the ICU and the general ward were compared. The patients were divided into shockable and non-shockable rhythm groups, and the differences between the two groups were compared. Finally, we proposed a management protocol for cardiac arrest in the general ward. Results We retrospectively analyzed 41,450 patients who underwent CABG only, of whom 231 (0.56%) experienced cardiac arrest post-surgery in the ICU (185/231) or in the general ward (46/231). The rescue success rate and 30-day survival rate of the patients with cardiac arrest in the general ward were 76.1% (35/46) and 58.7% (27/46), respectively. The incidence of the different arrhythmia types of cardiac arrest in the general ward compared with that in the ICU was different (P = 0.010). The 30-day survival rate of the non-shockable rhythm group was 31.8% (7/22), which was worse than that of the shockable rhythm group (83.3% [20/24]; P = 0.001). Kaplan–Meier survival analysis showed that the prognosis of the non-shockable group was poor (P

Abstract Background Radioresistance is the leading cause of death in advanced cervical cancer (CC). Dysregulation of RNA modification has recently emerged as a regulatory mechanism in radiation and drug resistance. We aimed to explore the biological function and clinical significance of 5-methylcytosine (m5C) in cervical cancer radiosensitivity. Methods The abundance of RNA modification in radiotherapy-resistant and sensitive CC specimens was quantified by liquid chromatography-tandem mass spectrometry. The essential RNA modification-related genes involved in CC radiosensitivity were screened via RNA sequencing. The effect of NSUN6 on radiosensitivity was verified in CC cell lines, cell-derived xenograft (CDX), and 3D bioprinted patient-derived organoid (PDO). The mechanisms of NSUN6 in regulating CC radiosensitivity were investigated by integrative m5C sequencing, mRNA sequencing, and RNA immunoprecipitation. Results We found a higher abundance of m5C modification in resistant CC samples, and NSUN6 was the essential m5C-regulating gene concerning radiosensitivity. NSUN6 overexpression was clinically correlated with radioresistance and poor prognosis in cervical cancer. Functionally, higher NSUN6 expression was associated with radioresistance in the 3D PDO model of cervical cancer. Moreover, silencing NSUN6 increased CC radiosensitivity in vivo and in vitro. Mechanistically, NDRG1 was one of the downstream target genes of NSUN6 identified by integrated m5C-seq, mRNA-seq, and functional validation. NSUN6 promoted the m5C modification of NDRG1 mRNA, and the m5C reader ALYREF bound explicitly to the m5C-labeled NDRG1 mRNA and enhanced NDRG1 mRNA stability. NDRG1 overexpression promoted homologous recombination-mediated DNA repair, which in turn led to radioresistance in cervical cancer. Conclusions Aberrant m5C hypermethylation and NSUN6 overexpression drive resistance to radiotherapy in cervical cancer. Elevated NSUN6 expression promotes radioresistance in cervical cancer by activating the NSUN6/ALYREF-m5C-NDRG1 pathway. The low expression of NSUN6 in cervical cancer indicates sensitivity to radiotherapy and a better prognosis.

Abstract Background Despite evidence supporting the high correlation of the novel platelet-to-albumin ratio (PAR) with survival in diverse malignancies, its prognostic relevance in nasopharyngeal carcinoma (NPC) remains underexplored. This study aimed to examine the link between PAR and overall survival (OS) in NPC and to establish a predictive model based on this biomarker. Methods We retrospectively assembled a cohort consisting of 858 NPC patients who underwent concurrent chemoradiotherapy (CCRT). Utilizing the maximally selected log-rank method, we ascertained the optimal cut-off point for the PAR. Subsequently, univariate and multivariate Cox proportional hazards models were employed to discern factors significantly associated with OS and to construct a predictive nomogram. Further, we subjected the nomogram’s predictive accuracy to rigorous independent validation. Results The discriminative optimal PAR threshold was determined to be 4.47, effectively stratifying NPC patients into two prognostically distinct subgroups (hazard ratio [HR] = 0.53; 95% confidence interval [CI]: 0.28–0.98, P = 0.042). A predictive nomogram was formulated using the results from multivariate analysis, which revealed age greater than 45 years, T stage, N stage, and PAR score as independent predictors of OS. The nomogram demonstrated a commendable predictive capability for OS, with a C-index of 0.69 (95% CI: 0.64–0.75), surpassing the performance of the conventional staging system, which had a C-index of 0.56 (95% CI: 0.65–0.74). Conclusions In the context of NPC patients undergoing CCRT, the novel nutritional-inflammatory biomarker PAR emerges as a promising, cost-efficient, easily accessible, non-invasive, and potentially valuable predictor of prognosis. The predictive efficacy of the nomogram incorporating the PAR score exceeded that of the conventional staging approach, thereby indicating its potential as an enhanced prognostic tool in this clinical setting.

Abstract Effects of short-term exposure to ambient air pollution on systemic immunological and inflammatory biomarkers in rural population have not been adequately characterized. From May to July 2021, 5816 participants in rural villages of northern Henan Province, China, participated in this cross-sectional study. Blood biomarkers of systemic inflammation were determined including peripheral white blood cells (WBC), eosinophils (EOS), basophils (BAS), monocytes (MON), lymphocytes (LYM), neutrophils (NEU), neutrophil-lymphocyte ratio (NLR), and serum high-sensitivity C-reactive protein (hs-CRP). The concentrations of ambient fine particulate matter (PM2.5), PM10, nitrogen dioxide (NO2), carbon monoxide (CO), and ozone (O3) were assessed up to 7 days prior to the blood draw. A generalized linear model was used to analyze the associations between air pollution exposure and the above-mentioned blood biomarkers. Significantly positive associations were revealed between PM2.5, CO and WBC; CO, O3 and LYM; PM2.5, PM10, SO2, CO and NEU; PM2.5, PM10, SO2, CO and NLR; PM2.5, PM10, SO2, NO2, CO, O3 and hs-CRP. Meanwhile, negative associations were found between SO2 and WBC; PM2.5, PM10, NO2, CO, or O3 and EOS; PM2.5, SO2, or CO and BAS; SO2, NO2 or O3 and MON; PM2.5, PM10, SO2, or NO2 and LYM. Moreover, men, individuals with normal body mass index (BMI), current smokers, and those older than 60 years were found vulnerable to air pollution effects. Taken together, short-term exposure to air pollution was associated with systemic inflammatory responses, providing insight into the potential mechanisms for air pollution-induced detrimental systemic effects in rural residents.

Abstract GPRC5D is an atypical Class C orphan G protein-coupled receptor. Its high expression on the surface of multiple myeloma cells has rendered it an attractive target for therapeutic interventions, including monoclonal antibodies, CAR-T cells, and T-cell engagers. Despite its therapeutic potential, the insufficient understanding regarding of the receptor’s structure and antibody recognition mechanism has impeded the progress of effective therapeutic development. Here, we present the structure of GPRC5D in complex with a preclinical-stage single-chain antibody (scFv). Our structural analysis reveals that the GPRC5D presents a close resemblance to the typical Class C GPCRs in the transmembrane region. We identify a distinct head-to-head homodimer arrangement and interface mainly involving TM4, setting it apart from other Class C homo- or hetero-dimers. Furthermore, we elucidate the binding site engaging a sizable extracellular domain on GPRC5D for scFv recognition. These insights not only unveil the distinctive dimer organization of this unconventional Class C GPCR but also hold the potential to advance drug development targeting GPRC5D for the treatment of multiple myeloma.

Abstract Human epidermal growth factor receptor 2-positive (HER2+) breast cancer (BC) patients are at a high risk of developing metastases in the brain. However, research focusing on treatment strategies for hormonal receptor positive (HR+), HER2+ BC patients with brain metastases (BM) remains limited. Thus, a multi-center, prospective trial was conducted in China. Women over the age of 18 who were naive to whole brain radiotherapy and had estrogen receptor (ER)/progesterone-receptor (PgR) positive, HER2+ BM were treated with palbociclib, fulvestrant, trastuzumab and pyrotinib, until disease progression or the development of intolerable side effects. The primary endpoint was objective response rate (ORR) in the central nervous system (CNS). This ongoing study is still recruiting participants and is registered with ClinicalTrials.gov (NCT04334330). This report presents the findings from an interim analysis. From December 4, 2020, to November 2, 2022, 15 patients were enrolled. Among the 14 patients who were evaluable for clinical response, the ORR was 35.7% (95% CI: 12.8–64.9%), with a CNS–ORR of 28.6% (95% CI: 8.4–58.1%). The median follow-up period was 6.3 months (range, 2.1–14.3 months), during which the median progression-free survival (PFS) was 10.6 months (95% CI: 4.3–16.9 months), and the median time to CNS progression was 8.5 months (95% CI: 5.9–11.1 months). The most common adverse event was diarrhea (93%), with 33% having grade 3 and 6.7% having grade 4. The study suggests that the combination of palbociclib, trastuzumab, pyrotinib and fulvestrant offers a promising chemo-free treatment strategy for HR+, HER2+ BC patients with BM.

Abstract The importance of fuel mixing for the progress of the scramjet engine is indisputable. The present article shows the importance of the non-equal multi-injector system for effective fuel distribution and flame holding inside the combustion segment of a scramjet engine. The supersonic air and fuel jet flow in the non-equal nozzle arrangement is simulated via computational fluid dynamic technique. Two injector types of circular and rectangular nozzle have been analyzed to attain flow characteristics of hydrogen jets at supersonic cross flow. Mach contour is also analyzed for these jet arrangements to show the interface of the jet in the non-equal jet arrangement. Besides, addition of internal air jet is also simulated and evaluated in this research. Our investigation shows that the diffusion height of the fuel jet is higher when a rectangular non-equal nozzle is applied. The circular nozzle is more active in the spreading of the fuel in the combustor and the use of an internal air jet effectively increases fuel in a combustor of the scramjet.

Abstract Background Factor XI (FXI) deficiency is an autosomal hemorrhagic disorder characterized by reduced plasma FXI levels. Multiple ancestral variants in the F11 gene have been identified in Ashkenazi Jews and other selected European populations. However, there are few reports of predominant variants in Chinese and/or East Asian populations. The aim of this study is to characterize the genotypes and phenotypes of FXI deficiency and identify the predominant variants. Results Of the 41 FXI-deficient patients, 39 exhibited severe FXI defects, considerably more than those with partial defects. The APTT levels showed a negative correlation with FXI activity levels (coefficient=-0.584, P

The Lower Silurian Longmaxi Formation on the southwestern margin of the Sichuan Basin holds significant shale gas reserves. The characteristics and formation stages of fractures play a crucial role in shale gas accumulation and productivity. Focusing on the Longmaxi Formation in the Tiangongtang area, this study employed core analysis, FMI (Formation Micro-Imager) logging, rock acoustic emission experiments, carbon-oxygen isotope analysis of fracture fillings, fluid inclusion homogenization temperature testing, and burial-thermal evolution history analysis to investigate the development characteristics and formation periods of natural fractures in the shale. The results indicate that the natural fractures in the Longmaxi Formation in the study area are characterized by the coexistence of tectonic vertical and low-angle fractures. The core fractures exhibit high development density, short extension, and high filling degree. Comparison of imaging log fracture dip angles, core fracture cross-cutting relationships, fracture filling fluid inclusion tests, and rock acoustic emission experiments suggested that the fractures in the Longmaxi Formation in the Tiangongtang area were associated with three tectonic events. Combined with burial-thermal evolution history analysis, the formation periods were confirmed as follows: the first stage involved NW-oriented and NNE-oriented planar shear fractures, and NEE-oriented cross-sectional shear fractures formed during the mid-late Yanshanian period (130-62 Ma) with tectonic stress orientation near SN (345°±5°) and inclusion homogenization temperatures of 185-206 ℃; the second stage involved NE-oriented and NW-oriented planar shear fractures, and NNW-trending cross-sectional shear fractures formed during the late Yanshanian to mid-Himalayan period (62-34 Ma) with tectonic stress orientation near EW (80°±5°) and inclusion homogenization temperatures of 165-184 ℃; the third stage involved near SN-oriented and NEE-oriented planar shear fractures, and NE-oriented cross-sectional shear fractures formed from the mid-Himalayan period to present (34 Ma to present) with tectonic stress orientation near NW (315°±5°) and inclusion homogenization temperatures of 125-162 ℃. Based on the geomechanical background, a three-stage tectonic fracture evolution model for the Longmaxi Formation in the Tiangongtang area was established.

Abstract Background It was reported the paraspinal muscle played an important role in spinal stability. The preoperative paraspinal muscle was related to S1 screw loosening. But the relationship between preoperative and postoperative change of psoas major muscle (PS) and S1 pedicle screw loosening in degenerative lumbar spinal stenosis (DLSS) patients has not been reported. This study investigated the effects of preoperative and follow-up variations in the psoas major muscle (PS) on the first sacral vertebra (S1) screw loosening in patients with DLSS. Methods 212 patients with DLSS who underwent lumbar surgery were included. The patients were divided into the S1 screw loosening group and the S1 screw non-loosening group. Muscle parameters were measured preoperatively and at last follow-up magnetic resonance imaging. A logistic regression analysis was performed to investigate the risk factors for S1 screw loosening. Results The S1 screw loosening rate was 36.32% (77/212). The relative total cross-sectional areas and relative functional cross-sectional areas (rfCSAs) of the PS at L2–S1 were significantly higher after surgery. The increased rfCSA values of the PS at L3–S1 in the S1 screw non-loosening group were significantly higher than those in the S1 screw loosening group. The regression analysis showed male, lower CT value of L1 and longer segment fusion were independent risk factors for S1 screw loosening, and postoperative hypertrophy of the PS was a protective factor for S1 screw loosening. Conclusions Compared to the preoperative muscle, the PS size increased and fatty infiltration decreased after surgery from L2–3 to L5–S1 in patients with DLSS after short-segment lumbar fusion surgery. Postoperative hypertrophy of the PS might be considered as a protective factor for S1 screw loosening. MRI morphometric parameters and postoperative selected exercise of PS for DLSS patients after posterior lumbar fusion surgery might contribute to improvement of surgical outcome.

Abstract Background Poly (ADP-ribose) polymerase inhibitor (PARPi) resistance poses a significant challenge in ovarian carcinoma (OC). While the role of DOT1L in cancer and chemoresistance is acknowledged, its specific role in PARPi resistance remains unclear. This study aims to elucidate the molecular mechanism of DOT1L in PARPi resistance in OC patients. Methods This study analyzed the expression of DOT1L in PARPi-resistant cell lines compared to sensitive ones and correlated it with clinical outcomes in OC patients. Comprehensive in vitro and in vivo functional experiments were conducted using cellular and mouse models. Molecular investigations, including RNA sequencing, chromatin immunoprecipitation (ChIP) and Cleavage Under Targets and Tagmentation (CUT&Tag) assays, were employed to unravel the molecular mechanisms of DOT1L-mediated PARPi resistance. Results Our investigation revealed a robust correlation between DOT1L expression and clinical PARPi resistance in non-BRCA mutated OC cells. Upregulated DOT1L expression in PARPi-resistant tissues was associated with diminished survival in OC patients. Mechanistically, we identified that PARP1 directly binds to the DOT1L gene promoter, promoting transcription independently of its enzyme activity. PARP1 trapping induced by PARPi treatment amplified this binding, enhancing DOT1L transcription and contributing to drug resistance. Sequencing analysis revealed that DOT1L plays a crucial role in the transcriptional regulation of PLCG2 and ABCB1 via H3K79me2. This established the PARP1-DOT1L-PLCG2/ABCB1 axis as a key contributor to PARPi resistance. Furthermore, we discovered that combining a DOT1L inhibitor with PARPi demonstrated a synergistic effect in both cell line-derived xenograft mouse models (CDXs) and patient-derived organoids (PDOs). Conclusions Our results demonstrate that DOT1L is an independent prognostic marker for OC patients. The PARP1-DOT1L/H3K79me2-PLCG2/ABCB1 axis is identified as a pivotal contributor to PARPi resistance. Targeted inhibition of DOT1L emerges as a promising therapeutic strategy for enhancing PARPi treatment outcomes in OC patients.

Abstract The purpose of this study was to explore the diagnostic implications of ubiquitination-related gene signatures in Alzheimer's disease. In this study, we first collected 161 samples from the GEO database (including 87 in the AD group and 74 in the normal group). Subsequently, through differential expression analysis and the iUUCD 2.0 database, we obtained 3450 Differentially Expressed Genes (DEGs) and 806 Ubiquitin-related genes (UbRGs). After taking the intersection, we obtained 128 UbR-DEGs. Secondly, by conducting GO and KEGG enrichment analysis on these 128 UbR-DEGs, we identified the main molecular functions and biological pathways related to AD. Furthermore, through the utilization of GSEA analysis, we have gained insight into the enrichment of functions and pathways within both the AD and normal groups. Further, using lasso regression analysis and cross-validation techniques, we identified 22 characteristic genes associated with AD. Subsequently, we constructed a logistic regression model and optimized it, resulting in the identification of 6 RUbR-DEGs: KLHL21, WDR82, DTX3L, UBTD2, CISH, and ATXN3L. In addition, the ROC result showed that the diagnostic model we built has excellent accuracy and reliability in identifying AD patients. Finally, we constructed a lncRNA-miRNA-mRNA (competing endogenous RNA, ceRNA) regulatory network for AD based on six RUbR-DEGs, further elucidating the interaction between UbRGs and lncRNA, miRNA. In conclusion, our findings will contribute to further understanding of the molecular pathogenesis of AD and provide a new perspective for AD risk prediction, early diagnosis and targeted therapy in the population.

ABSTRACT Aim This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. Materials and Methods A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial‐ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. Results The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend

Integration of aluminum (Al) and titanium (Ti) alloys offers an effective approach to sustainable and high-quality development of the automotive and aviation industries. However, challenges arise when welding Al alloys to Ti alloys due to the formation of detrimental intermetallic compounds at the interface. With the implementation of ultrasonic vibrations, the temperature and strain rate were both increased during Al/Ti friction stir welding (FSW), leading to the formation of an amorphous interlayer, instead of intermetallic compound (IMC), at the interface. The interfacial microcracks were eliminated in the ultrasonic vibrations assisted friction stir welding (UVFSW). There were Ti particles separated from the Ti substrate and dispersed in the Al alloy, thereby resulting in a more gradual and moderate evolution of the interfacial microstructure. Due to the improved interfacial microstructure with ultrasonic vibrations, the lap shear strength was almost twice that of the conventional FSW welds within same welding conditions. Meanwhile, ultrasonic vibrations also improved the fabrication efficiency with a higher optimal traversing speed. The failure mode shifted from interface separation of FSW welds to a shear dimple fracture of the UVFSW welds, demonstrating the better plasticity and reliability of the UVFSW Al/Ti dissimilar joints.

ObjectivesOur study aims to clarify the causality between air pollutants and lung function, chronic respiratory diseases, and the potential mediating effects of inflammatory proteins.MethodWe employed Mendelian Randomization (MR) analysis with comprehensive instrumental variables screening criteria to investigate the effects of air pollutants on lung function and chronic lung diseases. Our study incorporated genetic instruments for air pollutants, ensuring F-statistics above 20.86. A total of 18 MR analyses were conducted using the inverse-variance weighted approach, along with heterogeneity and pleiotropy tests to validate the results. Mediated MR analysis was utilized to evaluate the inflammatory proteins mediating the effects of air pollutants.ResultMR analysis demonstrated significant causal interactions of particulate matter 2.5 (PM2.5), PM10, and Nitrogen dioxide (NO2) with lung function decline. Specifically, PM10 negatively affected forced expiratory volume in one second (FEV1) (OR: 0.934, 95% CI: 0.904–0.965, p = 4.27 × 10−5), forced vital capacity (FVC) (OR: 0.941, 95% CI: 0.910–0.972, p = 2.86 × 10−4), and FEV1/FVC (OR: 0.965, 95% CI: 0.934–0.998, p = 0.036). PM2.5 and NO2 were identified as potential risk factors for impairing FEV1 (OR: 0.936, 95% CI: 0.879–0.998, p = 0.042) and FEV1/FVC (OR: 0.943, 95% CI: 0.896–0.992, p = 0.024), respectively. For chronic respiratory diseases, PM2.5 and NO2 were associated with increased COPD incidence (OR: 1.273, 95% CI: 1.053–1.541, p = 0.013 for PM2.5; OR: 1.357, 95% CI: 1.165–1.581, p = 8.74 × 10−5 for NO2). Sensitivity analyses confirmed the robustness of these findings, with no significant heterogeneity or horizontal pleiotropy detected.ConclusionOur study ascertained the causal correlations of air pollutants with lung function and COPD, emphasizing the importance of reducing air pollution. Interleukin-17A mediates the reduction of FEV1 and FVC by PM10, revealing potential therapeutic targets.

The interactions between human serum albumin (HSA) and the hemostatic components of the Chinese medicine Sanguisorbae Radix (SR), specifically phenolic acid compounds such as caffeic acid (CA), ferulic acid (FA) and their 1:1 mixture (1:1) were studied to investigate the molecular mechanism underlying the hemostatic effect of SR. Network pharmacology combined with the experimental and computational data revealed that HSA is one of the hemostatic targets to SR phenolic acids. SDS-PAGE and multi-spectroscopy demonstrated that the phenolic acids bind to the Sudlow site I on HSA, altering its structure and influencing its migration velocity. There is an observed synergistic effect upon the mixture of CA and FA. Quantum chemistry, molecular docking, and molecular dynamics simulations indicate that the binding of phenolic acids to HSA is stable, and variations in binding efficiency are associated with the hydrophobicity of the substituent at the C3 position of the side chain, and also, the key amino acids and functional groups for hemostasis of SR were identified, along with the active sites that contribute to the synergistic enhancement by phenolic acids.

High glycogen in oysters contributes to their flavor, quality, and hardiness, making it a crucial target trait for breeding purposes. Until now, the upstream regulatory mechanism for glycogen synthesis has remained unclear. Protein phosphatase-1 regulatory subunit 3 (PPP1R3) is a member of a family that directs the protein phosphatase-1 (PP1) to glycogen, resulting in the activation of glycogen synthase (GS) and the inactivation of glycogen phosphorylase (GP). However, their functions in molluscan species have remained unclear until now. In our study, we verified the function of the PP1α/PPP1R3D pathways in the glycogen metabolism process in Crassostrea gigas. Initially, we conducted a phylogenetic analysis and identified two PP1 and PPP1R3 members in molluscan species, emphasizing copy number variations in eukaryotic animals. Additionally, we identified distinct substitutions of conserved motifs specific to bivalves, Cephalopoda, or Gastropods, revealing functional diversity in PP1 and PPP1R3. Our primary focus was on PP1α/PPP1R3D in the oyster C.gigas, detected in the muscle glycogen fraction of bivalve species, with mRNA expression showing a positive correlation with glycogen content. By manipulating CgPPP1R3D expression in oysters through adenovirus-mediated overexpression or siRNA-mediated downregulation, we established a direct positive correlation between CgPPP1R3D expression levels and glycogen content. Colocation analysis confirmed protein interactions between CgPP1α and CgPPP1R3D. Furthermore, to elucidate the correlation between gene expression and glycogen accumulation, we conducted an association analysis and identified a cluster of significant SNP loci upstream of CgPPP1R3D significantly related to glycogen content. The high polymorphism observed may be linked to differential expressions of CgPPP1R3D in oyster individuals with high and low glycogen levels. These findings serve as a crucial reference for enhancing glycogen traits in molluscan species.

Background: The tumor microenvironment (TME) affected the prognosis of tumors. However, its effect on the outcomes of obese endometrial cancer (EC) patients had not been reported. Methods: This research performed a retrospective analysis of the transcriptome profiles and medical data of 503 EC patients. Immune scores were assessed by estimation algorithms. Cox and LASSO regression analyses were utilized to pinpoint key genes linked to prognosis, and the RPS was created to forecast the outcomes of obese EC patients. The relationship among genetic mutations and RPS was examined using CNV and somatic mutation information. ssGSEA and GSVA were employed to detect immune infiltration and immune pathway enrichment associated with key genes. The TIDE algorithm and GDSC database were utilized to forecast patients’ responses of patients to immunotherapy and chemotherapy, respectively. Finally, we employed the 'rms' R software package to construct the nomogram. Results: The prognosis of obese EC patients was associated with immune scores. Three key genes (EYA4, MBOAT2 and SCGB2A1) were identified. The risk prognosis score (RPS) for obese EC patients was established by risk stratification and prognostic prediction using prognostic genes. The higher the RPS, the worse the prognosis, and the more malignant the genomic alterations. The high RPS group had a significantly reduced proportion of most immune cells in comparison to the low RPS group. The high RPS group was linked to G2M, MYC and E2F related pathways such as cell proliferation, cell cycle and cell death. Cisplatin, tamoxifen and topotecan had a greater effect on the low RPS group. Notably, the nomogram had a good predictive ability. Conclusion: Our study designed a reliable RPS for obese EC patients to forecast their prognosis, immune aggressiveness, and responses to immunotherapy and drug treatments.

Purpose: Pure mucinous breast cancer (PMC) is a rare histological type with a favourable prognosis. However, cases with recurrence have been reported and diagnosed in clinical practice. The mechanisms underlying PMC recurrence remain unknown. In this study, we aimed to identify the prognostic factors associated with PMC. Materials and methods: A total of 166 patients diagnosed with PMC were included. We compared the clinicopathological characteristics between patients with and without recurrence. The 21-gene assay was performed in 10 patients with recurrence and 20 TNM stage-matched patients without recurrence. Whole-exon sequencing was performed in 12 PMC primary tumours and four positive lymph nodes (LNs). Results: Tumour size, lymph node status and TNM staging differed significantly between recurrent group and non-recurrent group. And the 21-gene recurrence scores did not differ significantly between recurrent group and its TNM stage-matched non-recurrent group. The most frequently mutated genes in the primary tumours of regional LN-positive PMCs were ADCY10 (3/6) and SHANK3 (3/6), and they more recurrently harboured gains of 15q23, 17q23.2 and 20p11.21, and loss of 21p11.2. And these alterations were not detected in primary tumours of regional LN-negative PMCs. Conclusion: TNM stage is an important prognostic factor in PMC. Although we revealed that regional LN-positive PMCs show increased occurrence of duplication variants at 15q23, 17q23.2 and 20p11.21, and deletion variants at 21p11.2. Further investigation, including multi-omics studies, are needed and may provide additional insights into the nature of PMC.

Background: To explore whether specific clinicopathological covariates are predictive for a benefit from capecitabine maintenance in early-stage triple-negative breast cancer (TNBC) in the SYSUCC-001 phase III clinical trial. Methods: Candidate covariates included age, menstrual status, type of surgery, postoperative chemotherapy regimen, Ki-67 percentage, histologic grade, primary tumor size, lymphovascular invasion, node status, and capecitabine medication. Their nonlinear effects were modeled by restricted cubic spline. The primary endpoint was disease-free survival (DFS). A survival prediction model was constructed using Cox proportional hazards regression analysis. Results: All 434 participants (306 in development cohort and 128 in validation cohort) were analyzed. The estimated 5-year DFS in development and validation cohorts were 77.8 % (95 % CI, 72.9%–82.7 %) and 78.2 % (95 % CI, 70.9%–85.5 %), respectively. Age and node status had significant nonlinear effects on DFS. The prediction model constructed using four covariates (node status, lymphovascular invasion, capecitabine maintenance, and age) demonstrated satisfactory calibration and fair discrimination ability, with C-index of 0.722 (95 % CI, 0.662–0.781) and 0.764 (95 % CI, 0.668–0.859) in development and validation cohorts, respectively. Moreover, patient classification was conducted according to their risk scores calculated using our model, in which, notable survival benefits were reported in low-risk subpopulations. An easy-to-use online calculator for predicting benefit of capecitabine maintenance was also designed. Conclusions: The evidence-based prediction model can be readily assessed at baseline, which might help decision making in clinical practice and optimize patient stratification, especially for those with low-risk, capecitabine maintenance might be a potential strategy in the early-disease setting.

Underground hydrogen storage (UHS) and compressed air energy storage (CAES) are two viable large-scale energy storage technologies for mitigating the intermittency of wind and solar power. Therefore, it is meaningful to compare the properties of hydrogen and air with typical thermodynamic storage processes. This study employs a multi-physical coupling model to compare the operations of CAES and UHS, integrating gas thermodynamics within caverns, thermal conduction, and mechanical deformation around rock caverns. Gas thermodynamic responses are validated using additional simulations and the field test data. Temperature and pressure variations of air and hydrogen within rock caverns exhibit similarities under both adiabatic and diabatic simulation modes. Hydrogen reaches higher temperature and pressure following gas charging stage compared to air, and the ideal gas assumption may lead to overestimation of gas temperature and pressure. Unlike steel lining of CAES, the sealing layer (fibre-reinforced plastic FRP) in UHS is prone to deformation but can effectively mitigates stress in the sealing layer. In CAES, the first principal stress on the surface of the sealing layer and concrete lining is tensile stress, whereas UHS exhibits compressive stress in the same areas. Our present research can provide references for the selection of energy storage methods.

Abstract Eye tracking techniques enable high-efficient, natural, and effortless human-machine interaction by detecting users’ eye movements and decoding their attention and intentions. Here, a miniature, imperceptible, and biocompatible smart contact lens is proposed for in situ eye tracking and wireless eye-machine interaction. Employing the frequency encoding strategy, the chip-free and battery-free lens successes in detecting eye movement and closure. Using a time-sequential eye tracking algorithm, the lens has a great angular accuracy of

Abstract Background This study investigated the clinical application of the indocyanine green (ICG) fluorescence navigation technique in bile duct identification during laparoscopic common bile duct exploration (LCBDE) for complex hepatolithiasis. Methods Eighty patients with complex hepatolithiasis were admitted to our department between January 2022 and June 2023 and randomly divided into control and observation groups. The control group underwent conventional LCBDE, while the observation group underwent LCBDE guided by ICG fluorescence. Results Intraoperatively, the observation group had shorter operation and search times for the common bile duct (CBD), as well as reduced intraoperative blood loss and fewer complications, such as conversion to laparotomy and various injuries (gastroduodenal, colon, pancreatic, and vascular) than the control group, with statistical significance (P

Abstract Background The surgical Apgar score (SAS) quantifying three intraoperative indexes has been confirmed to be significantly associated with postoperative morbidity and prognosis in many surgical specialties. However, there are great limitations in its application for esophageal cancer (EC). This study aimed to assess the predictive capability of esophagectomy SAS (eSAS) in determining postoperative morbidity and overall survival (OS) in EC patients who had undergone neoadjuvant therapy. Methods A retrospective evaluation was conducted on a cohort of 221 patients in which surgery‐ and tumor‐related data were extracted and analyzed. Major morbidity was defined as complications meeting the criteria of Clavien‐Dindo classification III or higher during hospitalization. Univariate and multivariate analyses were performed to identify potential risk factors for major morbidity. Kaplan–Meier analysis was utilized to calculate the OS and relapse‐free survival (RFS). Results The results exhibited that eSAS demonstrated potential predictive value for postoperative morbidity with an optimal cutoff value of 6. The eSAS and diabetes mellitus were two independent risk factors for the major morbidity; however, no correlation between the eSAS and the OS or RFS was detected. Conclusion The eSAS could be used as a predictor of major morbidity, while it was not correlated with OS and RFS.

Optical endoscopy has become an essential diagnostic and therapeutic approach in modern biomedicine for directly observing organs and tissues deep inside the human body, enabling non-invasive, rapid diagnosis and treatment. Optical fiber endoscopy is highly competitive among various endoscopic imaging techniques due to its high flexibility, compact structure, excellent resolution, and resistance to electromagnetic interference. Over the past decade, endoscopes based on a single multimode optical fiber (MMF) have attracted widespread research interest due to their potential to significantly reduce the footprint of optical fiber endoscopes and enhance imaging capabilities. In comparison with other imaging principles of MMF endoscopes, the scanning imaging method based on the wavefront shaping technique is highly developed and provides benefits including excellent imaging contrast, broad applicability to complex imaging scenarios, and good compatibility with various well-established scanning imaging modalities. In this review, various technical routes to achieve light focusing through MMF and procedures to conduct the scanning imaging of MMF endoscopes are introduced. The advancements in imaging performance enhancements, integrations of various imaging modalities with MMF scanning endoscopes, and applications are summarized. Challenges specific to this endoscopic imaging technology are analyzed, and potential remedies and avenues for future developments are discussed.

Abstract In next‐generation wireless communications, reconfigurable intelligent surface (RIS) has emerged as a cost‐effective technique for enhancing physical layer security (PLS) in millimeter‐wave (mmWave) communications, especially under challenging scenarios with adversarial entities and obstructions. However, the primary studies for RIS incorporation in mmWave communication systems utilized static deployments, lacking adaptability and efficiency in complex environments. To address this problem, a dynamic RIS deployment design framework is introduced for PLS enhancement in mmWave systems against jamming and eavesdropping attacks. For the design, it is aimed to maximize the secrecy rate by jointly optimizing the RIS selection with the beamforming design. The resulting optimization problem is challenging to solve due to the coupling of the RIS control factor, joint beamforming design, and non‐convex constraints. To tackle these issues, an efficient multi‐RIS‐aided PLS enhancement algorithm is proposed. It transforms the objective into a series of subproblems and employs the fractional programming technique and prox‐linear block coordinate descent updating method to solve them alternatively and obtain the optimal solution. The simulations demonstrate the advantage of the dynamic deployment, which exhibits enhanced security performance with reduced complexity compared with benchmarks. Further examinations also provide insight into optimal RIS activation configurations, achieving optimal balance for securing mmWave communications against emerging threats while maintaining system efficiency.

AbstractHericium erinaceus (Bull.:Fr.) Pers., 1797, is an edible and medicinal fungus found in China. In this study, specimens of H. erinaceus HE0021 were collected from southeastern China (Yunhe County, Lishui City, Zhejiang Province, 28°7′12″N, 119°34′12″E). The whole mitochondrial genome of H. erinaceus HE0021 was sequenced using next-generation sequencing (NGS) technology, which comprised 15 protein-coding genes (PCGs), 27 transfer RNAs (tRNAs), two ribosomal RNAs, with a total length of 83,518 base pairs (bp). The results of the phylogenetic analysis show that H. erinaceus and H. coralloides were clustered in the same clade. The complete mitogenome sequence provides essential data for the subsequent investigation of Hericium and Russulales.

Abstract Background Idiopathic pulmonary fibrosis (IPF) is a progressive disease with a five-year survival rate of less than 40%. There is significant variability in survival time among IPF patients, but the underlying mechanisms for this are not clear yet. Methods and results We collected single-cell RNA sequence data of 13,223 epithelial cells taken from 32 IPF patients and bulk RNA sequence data from 456 IPF patients in GEO. Based on unsupervised clustering analysis at the single-cell level and deconvolution algorithm at bulk RNA sequence data, we discovered a special alveolar type 2 cell subtype characterized by high expression of CCL20 (referred to as ATII-CCL20), and found that IPF patients with a higher proportion of ATII-CCL20 had worse prognoses. Furthermore, we uncovered the upregulation of immune cell infiltration and metabolic functions in IPF patients with a higher proportion of ATII-CCL20. Finally, the comprehensive decision tree and nomogram were constructed to optimize the risk stratification of IPF patients and provide a reference for accurate prognosis evaluation. Conclusions Our study by integrating single-cell and bulk RNA sequence data from IPF patients identified a special subtype of ATII cells, ATII-CCL20, which was found to be a risk cell subtype associated with poor prognosis in IPF patients. More importantly, the ATII-CCL20 cell subtype was linked with metabolic functions and immune infiltration.

Abstract Background Bladder cancer (BC) is one of the most common malignancies of the genitourinary system. Phosphofructokinase 1 (PFK-1) is one of member of PFK, which plays an important role in reprogramming cancer metabolism, such as lactylation modification. Zinc finger E-box-binding homeobox 1 (ZEB1) has been demonstrated to be a oncogene in many cancers. Therefore, this study was performed to explore the effects of PFK-1 on the lactylation of ZEB1 in BC development. Methods Cell viability was measured using the CCK-8 kit. The glucose assay kit and lactate assay kit were used to detect glucose utilization and lactate production. The DNA was purified and quantified by qRT-PCR. Results In the present study, we found that ZEB1 expression levels were significantly elevated in bladder cancer cells. Impaired PFK-1 expression inhibits proliferation, migration, and invasion of BC cells and suppresses tumour growth in vivo. We subsequently found that knockdown of PFK-1 decreases glycolysis, including reduced glucose consumption, lactate production and total extracellular acidification rate (ECAR). Mechanistically, PFK-1 inhibits histone lactylation of bladder cancer cells, and thus inhibits the transcription activity of ZEB1. Conclusion Our results suggest that PFK-1 can inhibit the malignant phenotype of bladder cancer cells by mediating the lactylation of ZEB1. These findings suggested PFK-1 to be a new potential target for bladder cancer therapy.

Abstract Pulmonary fibrosis (PF) is a progressive interstitial inflammatory disease with a high mortality rate. Patients with PF commonly experience a chronic dry cough and progressive dyspnoea for years without effective mitigation. The pathogenesis of PF is believed to be associated with dysfunctional macrophage polarization, fibroblast proliferation, and the loss of epithelial cells. Thus, it is of great importance and necessity to explore the interactions among macrophages, fibroblasts, and alveolar epithelial cells in lung fibrosis, as well as in the pro-fibrotic microenvironment. In this review, we discuss the latest studies that have investigated macrophage polarization and activation of non-immune cells in the context of PF pathogenesis and progression. Next, we discuss how profibrotic cellular crosstalk is promoted in the PF microenvironment by multiple cytokines, chemokines, and signalling pathways. And finally, we discuss the potential mechanisms of fibrogenesis development and efficient therapeutic strategies for the disease. Herein, we provide a comprehensive summary of the vital role of macrophage polarization in PF and its profibrotic crosstalk with fibroblasts and alveolar epithelial cells and suggest potential treatment strategies to target their cellular communication in the microenvironment.

Abstract Background To evaluate the postoperative morbidity and mortality of patients undergoing cardiovascular surgery during the 2022 nationwide Omicron variant infection wave in China. Methods This retrospective cohort study included 403 patients who underwent cardiovascular surgery for the first time during the 2022 wave of the pandemic within 1 month. Among them, 328 patients were preoperatively diagnosed with COVID-19 Omicron variant infection during the pandemic, and 75 patients were negative. The association between Omicron variant exposure and postoperative prognosis was explored by comparing patients with and without COVID-19 exposure. The primary outcome was in-hospital death after cardiovascular surgery. The secondary outcomes were major postoperative morbidity, including myocardial infarction (MI), acute kidney injury (AKI), postoperative mechanical ventilation hours, ICU stay hours, and postoperative length of stay. The data were analyzed using inverse probability of treatment weighting (IPTW) to minimize bias. Results We identified 403 patients who underwent cardiovascular surgery, 328 (81.39%) had Omicron variant infections. In total, 10 patients died in the hospital. Omicron variant infection was associated with a much greater risk of death during cardiovascular surgery after adjustment for IPTW (2.8% vs. 1.3%, adjusted OR 2.185, 95%CI = 1.193 to 10.251, P = 0.041). For major postoperative morbidity, there were no significant differences in terms of myocardial infarction between the two groups (adjusted OR = 0.861, 95%CI = 0.444 to 1.657, P = 0.653), acute kidney injury (adjusted OR = 1.157, 95%CI = 0.287 to 5.155, P = 0.820), postoperative mechanical ventilation hours (B -0.375, 95%CI=-8.438 to 7.808, P = 0.939), ICU stay hours (B 2.452, 95%CI=-13.269 to 8.419, P = 0.660) or postoperative stay (B -1.118, 95%CI=-2.237 to 1.154, P = 0.259) between the two groups. Conclusion Perioperative COVID-19 infection was associated with an increased risk of in-hospital death among patients who underwent cardiovascular surgery during the Omicron variant wave of the pandemic.

Abstract Cone‐beam computed tomography (CBCT) system can provide real‐time 3D images and fluoroscopy images of the region of interest during the operation. Some systems can even offer augmented fluoroscopy and puncture guidance. The use of CBCT for interventional pulmonary procedures has grown significantly in recent years, and numerous clinical studies have confirmed the technology's efficacy and safety in the diagnosis, localization, and treatment of pulmonary nodules. In order to optimize and standardize the technical specifications of CBCT and guide its application in clinical practice, the consensus statement has been organized and written in a collaborative effort by the Professional Committee on Interventional Pulmonology of China Association for Promotion of Health Science and Technology.

Abstract As the largest transporter family impacting on tumor genesis and development, the prognostic value of solute carrier (SLC) members has not been elucidated in colorectal cancer (CRC). We aimed to identify a prognostic signature from the SLC members and comprehensively analyze their roles in CRC. Firstly, we downloaded transcriptome data and clinical information of CRC samples from GEO (GSE39582) and TCGA as training and testing dataset, respectively. We extracted the expression matrix of SLC genes and established a prognostic model by univariate and multivariate Cox regression. Afterwards, the low-risk and high-risk group were identified. Then, the differences of prognosis traits, transcriptome features, clinical characteristics, immune infiltration and drug sensitivity between the two groups were explored. Furthermore, molecular subtyping was also implemented by non-negative matrix factorization (NMF). Finally, we studied the expression of the screened SLC genes in CRC tumor tissues and normal tissues as well as investigated the role of SLC12A2 by loss of function and gain of function. As a result, we developed a prognostic risk model based on the screened 6-SLC genes (SLC39A8, SLC2A3, SLC39A13, SLC35B1, SLC4A3, SLC12A2). Both in the training and testing sets, CRC patients in the high-risk group had the poorer prognosis and were in the more advanced pathological stage. What’s more, the high-risk group were enriched with CRC progression signatures and immune infiltration. Two groups showed different drug sensitivity. On the other hand, two distinct subclasses (C1 and C2) were identified based on the 6 SLC genes. CRC patients in the high-risk group and C1 subtype had a worse prognosis. Furthermore, we found and validated that SLC12A2 was steadily upregulated in CRC. A loss-of-function study showed that knockdown of SLC12A2 expression restrained proliferation and stemness of CRC cells while a gain-of-function study showed the contrary results. Hence, we provided a 6-SLC gene signature for prognosis prediction of CRC patients. At the same time, we identified that SLC12A2 could promote tumor progression in CRC, which may serve as a potential therapeutic target.

Abstract Autophagy is a self-renewal mechanism that maintains homeostasis and can promote tissue regeneration by regulating inflammation, reducing oxidative stress and promoting cell differentiation. The interaction between biomaterials and tissue cells significantly affects biomaterial-tissue integration and tissue regeneration. In recent years, it has been found that biomaterials can affect various processes related to tissue regeneration by regulating autophagy. The utilization of biomaterials in a controlled environment has become a prominent approach for enhancing the tissue regeneration capabilities. This involves the regulation of autophagy in diverse cell types implicated in tissue regeneration, encompassing the modulation of inflammatory responses, oxidative stress, cell differentiation, proliferation, migration, apoptosis, and extracellular matrix formation. In addition, biomaterials possess the potential to serve as carriers for drug delivery, enabling the regulation of autophagy by either activating or inhibiting its processes. This review summarizes the relationship between autophagy and tissue regeneration and discusses the role of biomaterial-based autophagy in tissue regeneration. In addition, recent advanced technologies used to design autophagy-modulating biomaterials are summarized, and rational design of biomaterials for providing controlled autophagy regulation via modification of the chemistry and surface of biomaterials and incorporation of cells and molecules is discussed. A better understanding of biomaterial-based autophagy and tissue regeneration, as well as the underlying molecular mechanisms, may lead to new possibilities for promoting tissue regeneration. Video Abstract

Abstract Introduction To investigate the association between alcohol drinking and glycemic management among adult patients with type 2 diabetes in regional China. Materials and Methods In this cross‐sectional survey conducted in Nanjing Municipality of China in 2018, adult type 2 diabetes patients were randomly selected from urban and rural communities. The outcome variable was the glycemic management status. The explanatory measure was alcohol drinking. Mixed‐effects regression models were employed to estimate odds ratios (ORs) and 95% confidence interval (95% CI) for examining the associations of alcohol drinking with glycemic management among type 2 diabetes patients. Results Among the overall 5,663 participants, the glycemic management rate was 39.8% (95% CI = 38.5, 41.1), with 41.2% (95% CI = 39.7, 42.7), 43.9% (95% CI = 38.9, 48.8), and 34.1% (95% CI = 31.5, 36.7) for non‐drinkers, mild/moderate drinkers, and heavy drinkers, respectively. After adjustment for potential confounders and community‐level clustering effect, heavy and mild/moderate alcohol drinkers were at 0.76 (95% CI = 0.66, 0.89) and 1.04 (95% CI = 0.87, 1.28) times odds to have glycemia under control than non‐drinkers among the overall participants. Furthermore, when stratified separately by gender and use of anti‐diabetes agents, the scenario within men, either regular or irregular users of anti‐diabetes agents was the same as that for overall participants, while the association between alcohol drinking and glycemic management became non‐significant among women. Conclusions Heavy alcohol drinking might have a negative effect on glycemic management among patients with type 2 diabetes irrespective of the use of anti‐diabetes agents in regional China. This study has important public health implications regarding precision intervention on patients' glycemia control for type 2 diabetes management.

Using CO2-derived dimethyl carbonate (DMC) instead of diphenyl carbonate (DPC) as a carbonyl source for synthesizing bio-based polycarbonates is a green and cost-effective route. However, the synthesis of high-performance polycarbonates via the DMC route remains challenging due to the poor reactivity and selectivity of DMC compared to DPC. Herein, we designed a series of highly active protic ionic liquid (PIL) catalysts for the synthesis of poly(isosorbide carbonate) (PIC) from DMC with ISB. The influences of the structures of anion and cation on the catalytic activity of PILs were systematically studied. Compared with the reported aprotic IL catalysts, the unique reactive hydrogen of the cation in PILs could form a strong hydrogen bond interaction with the carbonyl group of DMC, resulting in higher reactivity of the carbonyl carbon of DMC. Moreover, the nucleophilicity of the anion could be easily tuned by adjusting the pKa value, which effectively realized the balance of the reactivity difference between exo-OH and endo-OH in ISB. Among them, [DBUH][Im] showed the highest catalytic activity, and the weight-average molecular weight (Mw) and glass transition temperature of PIC reached 55,700 g/mol and 160 °C, respectively. Combined with NMR analyses and DFT calculations, the mechanism that exhibited the synergetic catalytic effect of anion-cation for the polymerization of DMC and ISB was presented.

Plankton, as an important part of the food chain in the river ecosystem, is sensitive to changes in the environment. To investigate the influence of plankton community structure on the aquatic ecosystem and further verify the applicability of biomanipulation, the midstream of the Jialing River was selected as the study area. A total of 149 species (varieties) from 7 phyla, 18 orders, 34 families, and 72 genera were identified for phytoplankton. A total of 48 species were found for zooplankton. The mean density of phytoplankton was 2.09 × 106 cells/L, and the mean density of zooplankton was 27.1 ind./L. Moreover, the mean values of the Shannon–Wiener diversity index (H′), Pielou homogeneity index (J′), and Margalef abundance index (D) for phytoplankton were 3.17, 0.76, and 4.47, respectively. The mean values of the Shannon–Wiener diversity index (H′), Pielou homogeneity index (J′), and Margalef abundance index (D) for zooplankton were 2.64, 0.92, and 5.07, respectively. Based on the diversity indices, the water quality was evaluated as oligo pollution to β-medium pollution level. Redundancy analysis (RDA) was used to explore the relationship between dominant plankton species and environmental factors. The RDA results show that the main environmental factors affecting the community structure of phytoplankton and zooplankton were water temperature (WT), electrical conductivity (EC), pH, total phosphorus (TP), and transparency (Secchi depth; SD). There were 17 functional groups in phytoplankton, which are X1, S1, Y, Y2, and so on. In zooplankton, there were six functional groups, which are Pmsl, Prsu, Pfif, Pmip, Lrsf and Lmic. Many articles have demonstrated the feasibility of using biological manipulation to control algae. The number of piscivorous fish in the midstream of the Jialing River had increased, and phytoplankton density in this survey was significantly decreased. The results show that traditional biomanipulation can be applied to this region, which can provide better scientific support for the future management of the aquatic environment in the Jialing River basin.

Aims: To examine the concurrent validity of the Chinese version of Physical Activity Neighborhood Environment Scale (PANES-CHN) among urban adults in regional China. Methods: With multistage sampling approaches, 801 eligible urban adults aged 35–74 years were recruited from Nanjing municipality of China between July and September of 2019. The neighbourhood built environment features were measured subjectively with PANES-CHN and objectively with geographic information system. The concurrent validity of PANES was assessed using Spearman’s correlations (rs). Results: Among the total 801 participants, the mean age was 54.4 (standard deviation = 11.5), while 48.7 % were men. Overall, of all the five objectively-measurable built environment characteristics, the Spearman correlations were examined significant between subjective and objective measurements for commercial facilities (item 2) (rs = 0.19, 95CI%=0.12, 0.25), recreational facilities (item 6) (rs = 0.10, 95CI%=0.02, 0.16), traffic junctions (item 12) (rs = 0.15, 95CI%=0.07, 0.22), medical/education facilities (item 17) (rs = 0.22, 95CI%=0.15, 0.29), but not for public transport stops. Similar scenarios were observed for participants aged 35–60 years, with sufficient physical activity, men or women. The rs value for medical/education facilities (item 17) was significantly higher in participants aged 35–59 years (0.28 vs. 0.13; p = 0.04) than those aged 60 + years. Conclusions: PANES-CHN generally has an acceptable validity for assessing built environment characteristics among urban adults in China, which implies that PANES-CHN can be used to measure built environment attributes in health-related population studies.