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Bang-Hua Zhang,1,2 Hao Liu,1,2 Yan Yuan,1,2 Xiao-Dong Weng,1 Yang Du,1 Hui Chen,1 Zhi-Yuan Chen,1 Lei Wang,1 Xiu-Heng Liu1 1Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Hubei Key Laboratory of Digestive System Disease, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Xiu-Heng Liu; Lei WangDepartment of Urology, Renmin Hospital of Wuhan University, No. 238 Jiefang Road, Wuhan, 430060, Hubei, People’s Republic of ChinaTel/Fax +86 27 8804 1911Email drliuxh@hotmail.com; drwanglei@whu.edu.cnBackground: Acute kidney injury (AKI) emerges as an acute and critical disease. Tripartite motif 8 (TRIM8), one number of the TRIM protein family, is proved to participate in ischemia/reperfusion (I/R) injury. However, whether TRIM8 is involved in renal I/R injury and the associated mechanisms are currently unclear.Purpose: This study aimed to investigate the precise role of TRIM8 and relevant mechanisms in renal I/R injury.Materials and Methods: In this study, human renal proximal tubular epithelial cells (HK-2 cells) underwent 12 hours of hypoxia and 2 h, 3 h or 4 h of reoxygenation to establish an in vitro hypoxia/reoxygenation (H/R) model. The siRNAs specific to TRIM8 (si-TRIM8) were transfected into HK-2 cells to knockdown TRIM8. The cell H/R model included various groups including Control, H/R, H/R+DMSO, H/R+NAC, si-NC+H/R, si-TRIM8+H/R and si-TRIM8+LY294002+H/R. The cell viability and levels of reactive oxygen species (ROS), hydrogen peroxide (H2O2), mRNA, apoptotic proteins, pyroptosis-related proteins and PI3K/AKT pathway-associated proteins were assessed.Results: In vitro, realtime-quantitative PCR and western-blot analysis showed that the mRNA and protein expression of TRIM8 were obviously upregulated after H/R treatment in HK-2 cells. Compared with the H/R model group, knockdown of TRIM8 significantly increased cell viability and reduced the levels of ROS, H2O2, apoptotic proteins (Cleaved caspasebase-3 and BAX) and pyroptosis-related proteins (NLRP3, ASC, Caspase-1, Caspase-11, IL-1β and GSDMD-N). Western-blot analysis also authenticated that PI3K/AKT pathway was activated after TRIM8 inhibition. The application of 5 mM N-acetyl-cysteine, one highly efficient ROS inhibitor, significantly suppressed the expression of apoptotic proteins and pyroptosis-related proteins. Moreover, the combined treatment of TRIM8 knockdown and LY294002 reversed the effects of inhibiting oxidative stress.Conclusion: Knockdown of TRIM8 can alleviate H/R-induced oxidative stress by triggering the PI3K/AKT pathway, thus attenuating pyropyosis and apoptosis in vitro.Keywords: TRIM8, renal I/R injury, oxidative stress, apoptosis, pyroptosis

Lijin Lin,1– 4,&ast; Ze Chen,4,5,&ast; Ting Ding,1,2,&ast; Hui Liu,4,6,&ast; Feng Zhou,4,7 Xuewei Huang,3,4 Xingyuan Zhang,4,8 Weifang Liu,4,8 Bing-Hong Zhang,9 Yufeng Yuan,10 Peng Zhang,4,8 Xiao-Jing Zhang,4,8 Zhi-Gang She,3,4 Jingjing Cai,4,11 Wenping Chen,1,2 Hongliang Li2– 4,7 1Department of Endocrinology, Huanggang Central Hospital, Huanggang, People’s Republic of China; 2Huanggang Institute of Translational Medicine, Huanggang, People’s Republic of China; 3Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 4Institute of Model Animal of Wuhan University, Wuhan, People’s Republic of China; 5Department of Cardiology, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 6Neonatology of Gastroenterology, Tongren Hospital of Wuhan University & Wuhan Third Hospital, Wuhan, People’s Republic of China; 7Medical Science Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 8Basic Medical School of Wuhan University, Wuhan, People’s Republic of China; 9Neonatology Department, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China; 10Department of Hepatobiliary and Pancreatic Surgery, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 11Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongliang Li; Wenping Chen Email lihl@whu.edu.cn; chenwenping@hgyy.org.cnPurpose: To analyze the impact of hyperglycemia on the clinical outcome of COVID-19 in patients with newly diagnosed diabetes (NDD).Patients and Methods: We performed a retrospective study of 3114 cases of COVID-19 without pre-existing diabetes, 351 of which had NDD, in Hubei Province, China. The Cox regression model was used to calculate the risk of adverse clinical outcomes comparing the NDD vs non-NDD group before and after propensity score-matched (PSM) analysis. Patients with NDD were further divided into a sustained hyperglycemia group, a fluctuating group, and a remitted group based on their blood glucose levels during hospitalization as well as into hypoglycemic agent users and nonusers.Results: Compared to the non-NDD individuals, individuals with NDD had a significantly increased risk of all-cause mortality (adjusted HR after PSM, 2.65; 95% CI, 1.49– 4.72; P = 0.001) and secondary outcomes involving organ damage during the 28-day follow-up period. Subgroup analyses indicated that among individuals with NDD, the individuals with remitted hyperglycemia had the lowest 28-day mortality, whereas those with sustained hyperglycemia had the highest (IRR 24.27; 95% CI, 3.21– 183.36; P < 0.001). Moreover, individuals treated with hypoglycemic agents had significantly lower all-cause mortality than those not treated with hypoglycemic agents (IRR 0.08; 95% CI, 0.01– 0.56; P < 0.001).Conclusion: Our study reinforces the clinical message that NDD is strongly associated with poor outcomes in COVID-19 patients. Furthermore, resolved hyperglycemia in the later phase of the disease and the use of hypoglycemic agents were associated with improved prognosis in patients with NDD.Keywords: COVID-19, newly diagnosed diabetes, hyperglycemia, prognosis, blood glucose

The anomalous Hall effect (AHE), and magnetic and electronic transport properties were investigated in a series of amorphous transition metal thin films - FexSi1-x, FexGe1-x, CoxGe1-x, CoxSi1-x, and Fe1-yCoySi. The experimental results are compared with density functional theory calculations of the density of Berry curvature and intrinsic anomalous Hall conductivity. In all samples, the longitudinal conductivity (σxx), magnetization (M), and Hall resistivity (ρxy) increase with increasing transition metal concentration; due to the structural disorder σxx is lower in all samples than a typical crystalline metal. In the systems with Fe as the transition metal (including Fe1-yCoySi), the magnetization and AHE are large and in some cases greater than the crystalline analog. In all samples, the AHE is dominated by the intrinsic mechanism, arising from a nonzero, locally derived Berry curvature. The anomalous Hall angle (AHA) (=σxy/σxx) is as large as 5% at low temperature. These results are compared with the AHAs reported in a broad range of crystalline and amorphous materials. Previous work has shown that in a typical crystalline ferromagnet the Hall conductivity (σxy) and σxx are correlated and are usually either both large or both small, resulting in an AHA that decreases with increasing σxy. By contrast, the AHA increases linearly with increasing σxy in the amorphous systems. This trend is attributed to a generally low σxx, while σxy varies and can be large. In the amorphous systems, σxx and σxy are not coupled, and there may thus exist the potential to further increase the AHA by increasing σxy.

Objective: To evaluate the applicability of the modified physiological and operative severity score for enumeration of mortality and morbidity (POSSUM) scoring system in predicting mortality in the patients undergoing hip joint arthroplasty.Methods: A total of 295 patients with hip fractures were analyzed using the modified POSSUM surgical scoring system. The mean ages of the patients were 66.59 years in the complicative group, 62.28 years in noncomplicative group, 77.89 years in the death group and 63.25 years in the living group, respectively. The comparisons between the observed and predicted morbidity, between the observed and predicted mortality were made within 30 days after operation.Results: The average physiological scores and operative severity scores was 18.96+/-4.83 and 13.47+/-2.01 in complicative group, while 15.65+/-3.66 and 11.74+/-2.26 in noncomplicative group (P less than 0.05). The average physiological scores and operative severity scores was 25.56+/-3.78 and 14.22+/-0.67 in death group, while 16.46+/-4.09 and 12.25+/-2.33 in living group (P less than 0.05). Though POSSUM scoring system over-predicted the overall risk of death, its estimate was very close in the high risk groups (larger than 10% ). There was perfect consistence between the observed and the predicted morbidity as calculated by published predictor equation for morbidity, and consistence for mortality in the high risk band.Conclusions: Modified POSSUM scoring system may be used to predict the morbidity in patients with hip fracture. Furthermore, POSSUM scoring system overpredicts the overall risk of death, but its estimate is close to the actual data in the high risk band (larger than 10%). [ABSTRACT FROM AUTHOR]

Objective: To analyze three reconstruction techniques and mid-term clinical outcomes of hip revision for acetabular bone defect after total hip arthroplasty (THA). Methods: This is a retrospective case series study. Included in the study were 109 patients (109 hips) with acetabular bone defect after THA reconstructions in hip revisions from January 2015 to December 2021 in the Senior Department of Orthopaedics, the Forth Medical Center of Chinese People's Liberation Army General Hospital and the Department of Orthopaedics, the First Medical Center of Chinese People's Liberation Army General Hospital. According to the preoperative simulated surgeries and different bone defect reconstruction techniques, patients were divided into a normal cup group, an augment group or a triflange group,respectively. There were 54 patients (54 hips) in the normal cup group, reconstructed with the uncemented porous metal cup (including Jumbo cup), with 23 males and 31 females, aged (59.6±9.9) years (range:32 to 76 years); 44 patients (44 hips) in the augment group, reconstructed with the individualized three-dimensional (3D) printed porous metal augment and uncemented porous metal cup, with 18 males and 26 females, aged (52.8±13.6) years(range:17 to 76 years); 11 patients (11 hips) in the triflange group, reconstructed by the individualized 3D printed porous metal triflange cup, with 5 males and 6 females, aged (59.4±11.2) years (range: 43 to 78 years). Radiographic results, including rotation center height, rotation center offset, and leg length discrepancy (LLD) and clinical results, including Harris hip score (HHS) and visual analogue scale(VAS) were evaluated outpatient at 3, 6, 12 months after the operation and annually thereafter. The last follow-up was completed in March 2024, and all parameters at the last follow-up and before the operation were compared. Paired sample t test and repeated measurement ANOVA were used for the radiographic and clinical parameters before and after the operation. Results: All hip revisions for patients with acetabular bone defect after THA were completed and followed for more than two years. The follow-up time of the normal cup group was (6.5±1.7) years (range: 2.8 to 9.3 years), and that of the augment group was (6.0±1.3) years (range: 3.5 to 9.0 years). The follow-up time of the triflange group was (2.8±0.6) years (range: 2.0 to 3.8 years). At the last follow-up, the rotation center height, rotation center offset and LLD of 54 hips in the normal cup group were (24.2±5.6) mm, (29.1±5.5) mm and (4.6±3.3) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t =9.671, P <0.01; t =6.073, P <0.01). In the augment group, the rotational center height, the rotation center offset and the LLD of 44 hips were (22.4±9.0) mm, (25.4±5.5) mm and (6.0±4.0) mm, respectively, which were significantly lower than those of the preoperative hips ( t =9.071, P <0.01; t =11.345, P <0.01; t =4.927, P <0.01). In the triflange group, the rotational center height, the rotation center offset and LLD of 11 hips were (22.7±6.0) mm,(30.9±8.0) mm and (5.3±2.2) mm, respectively, and the rotation center height and LLD were significantly lower than those of the preoperative hips ( t =2.716, P =0.022; t =6.226, P <0.01). At the last follow-up, fractures occurred in 3 patients and dislocation occurred in 1 patient in the normal cup group, and fracture reduction and closed reduction were administered under anesthesia, respectively. In the augment group, dislocation occurred in 1 patient and open reduction under anesthesia was performed. The HHS and VAS of the three groups improved significantly after surgery and the differences were statistically significant (all P <0.01). There was no complication in the triflange group. The X-ray at the last follow-up showed that all prostheses and augments were in stable positions and no loosening or migration was observed. Conclusions: For patients with acetabular bone defect after THA undergoing hip revisions, preoperative surgical simulation and rehearsal could help surgeons choose convenient and efficient reconstruction techniques. The targeted selection of Jumbo cup, individualized 3D printed metal augment, and customized triflange cup could achieve satisfactory clinical outcomes.

Transition-metal sulfide is considered to be an admirable transformational electrode material due to low cost, large specific capacity, and good reversibility in lithium-ion batteries (LIBs) and sodium-ion batteries (SIBs). Herein, the reduced graphene oxide-wrapped open bimetallic sulfide (NiS 2 -Co 3 S 4 @rGO) nanocage, derived from nickel-cobalt Prussian blue, was obtained by two-step calcination. There are luxuriant pore structures in the nanocage composite with a specific surface area of 85.28 m 2 g -1 , which provides plentiful paths for rapid transmission of Li + /Na + and alleviates the volume stress caused by insertion and extraction of alkali metal ions. The excellent interface combination of bimetallic sulfide wrapped in reduced graphene oxide improves the conductivity and overall performance of the battery. Thanks to the special interface engineering, the open NiS 2 -Co 3 S 4 @rGO nanocage composite displays rapid lithium storage properties with an average diffusion coefficient of 8.5 × 10 -13 cm 2 s -1 . Moreover, after 300 cycles, the reversible capacity of the composite is 1113.2 mAh g -1 at 1 A g -1 . In SIBs, the capacity of the open NiS 2 -Co 3 S 4 @rGO composite is 487.9 mAh g -1 when the current density is 5 A g -1 . These preeminent performances demonstrate the enormous development prospects of bimetallic sulfide nanocage as anode material in LIBs and SIBs.

Yellowhorn (Xanthoceras sorbifolium) is a deciduous shrub or small tree native to China. The content of oil in kernels is 52.7% to 58.0%, of which is the source of neuroic acid (3.7-4.4%). (Liang et al. 2022). In recent years, yellowhorn, as a woody oleiferous crop, has been cultivated in northern China (Xiao et al. 2023). In late June 2019, an unknown collar rot was observed on yellowhorn in Tai'an, and Weifang City, Shandong Province, China. Infected plants had dark brown to black lesions at the base of the stem, about 10 to 15 cm from the ground, bark dehiscence and rot, resulting in wilting, withering, and death of plants. The disease incidence in the field was 35-48%. Representative symptomatic samples were collected randomly from the collar of 8 plants, and 24 samples were cut from the diseased tissue into 5 mm square pieces, surface disinfected with 75% alcohol for 30s and then with 0.1% mercury bichloride for 1min, plated onto potato dextrose agar (PDA), and incubated at 28°C in the dark for 2 to 3 days. Isolation frequency of the pathogen from symptomatic collar was 83.3%. The colonies were subcultured three times on PDA to obtained the purified colonies. The colonies appeared flocculent mycelia incubated on PDA at 28°C for 7 days. The color of the surface and the reverse colony was white and cream, respectively. The chlamydosposres were smooth with thick walled, and are formed singly. Microconidia were oval or ellipsoidal, with 0-1 septum; macroconidia end cells curved to slightly, with 3- or 5-septate, and measured 17.3 to 23.1 × 4.9 to 6.5 µm (avg. 21.3 × 5.9 μm, n = 60). The morphological characteristics fit the descriptions of Fusarium spp. (Hafizi et al. 2013; Crespo et al 2019). Genomic DNA extracted from four representative isolates (XSTA4, XSTA7, XSWF6 and XSWF8), and the internal transcribed spacer region (ITS) of ribosomal DNA, translation elongation factor 1-alpha (EF1-α), RNA polymerase I beta subunit (RPB1), and RNA polymerase II beta subunit (RPB2) genes were amplified using the primer pairs ITS1/ITS4 (White et al. 1990), EF-1/EF-2, RPB-1F/1R, and RPB2-5F2/11aR (O'Donnell et al 2010), respectively. Amplicons were sequenced and compared in GenBank using a BLAST analysis. The ITS sequences (OR672118, OR669008, OR669039, and OR669279) had 100% similarity with the sequences of F. solani (MT560378, MG561938, MN989030 and OP630608, respectively). The EF1-α sequences (OR934984, OR934985, OR934986, and OR934987) matched 100% with the sequences of F. solani (OQ511088, MW332044, MW620166 and MT379886). The RPB-1 sequences (PP896852, PP896853, PP896854, and PP896855) had 100% similarity with the sequences of F. solani (OL474057, OR916019, MT305118 and MT305118, respectively). The RPB2 sequences (PP896856, PP896857, PP896858, and PP896859) matched 100% with the sequences of F. solani (OR371884, OK880266, OP784447 and OL474055, respectively). A phylogenetic analysis based on ITS, RPB2 and EF1-α sequences placed the four obtained isolates within the same clade containing the F. solani isolates A6, 91-84-1 and UCR1780. Pathogenicity tests were carried out in late-June 2020. Fifty 120-day-old healthy seedlings were wounded with 2 mm deep at stems in the collar region of plants at 5 cm above the soil for tested. The seedlings were inoculated on the wound with 3-mm mycelial discs from a 7-day-old culture of each four representative strains of 10 repeated, respectively. Ten seedlings inoculated on the wound with sterile PDA served as control. All plants were grown in an incubator with a 28°C temperature. After 20 days, the stems which were inoculated the representative strain turned brown, with 2 - 5 cm length lesion, and the plants developed typical wilting and withering symptoms which similar to those observed in the field. The control remained asymptomatic. The pathogen was reisolated from the inoculated stems and its identity confirmed with both morphology and using molecular tools. These results indicated that the pathogens of yellowhorn collar rot is F. solani. To our knowledge, this is the first report of F. solani causing collar rot of yellowhorn in China.

Objective: To evaluate the prevalence, intervention methods and effect of arteriovenous graft (AVG) stenosis. Methods: The clinical data of patients who received AVG in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. The patency rate, prevalence and intervention effect of AVG stenosis were analyzed. Results: A total of 475 patients aged (55.5±11.8) years were included, and there were 193 male cases (40.6%) and 282 female cases (59.4%). The patients were followed up for [ M ( Q 1 , Q 3 )] 19 (12, 30) months, and the primary, assisted primary and secondary patency were 14 (5, 27), 27 (13, 55), and 59 (33, 65) months, respectively. There were 799 access events which needed intervention, with a total standardized intervention rate of 0.90 per patient-year. Totally, 431(53.9%, 431/799) stenosis events occurred in 207 AVG. Among 422 AVG stenosis events with complete clinical data, 57.8% (244/422) were multi-site stenosis and 42.2% (178/422) were single-site stenosis. The most common sites of stenosis were graft-vein anastomosis (47.6%, 340/715), venous outflows (22.7%, 162/715), and puncture zone (20.0%, 143/715). In the 414 stenosis with intact follow-up data, 90.8% (376/414) were treated by balloon angioplasty, 8.5% (35/414) received covered stent insertion, and 0.7% (3/414) were intervened by open surgery. Clinical success rate was 98.1% (406/414). The primary patency time after endovascular treatment was 6 (4, 12) months. Covered stent significantly increased post-intervention primary patency time compared withballoon angioplasty [6 (3, 7) months vs 3 (1, 4) months, P =0.020]. Conclusions: Stenosis is the most common complication of AVG, and the most common sites are graft-vein anastomosis, venous outflows, and puncture zone. Intervention of AVG stenosis has a high clinical success rate, and a relatively low post-intervention patency. Covered stent insertion improves the post-intervention patency of AVG, which has a poor effect using balloon expansion.

Background: Eosinophilic solid and cystic (ESC) renal cell carcinoma (RCC), a unique and emerging subtype of RCC, has an indolent nature; in some rare instances, it may exhibit metastatic potential. Current cases are inadequate to precisely predict the clinical outcome of ESC RCC and determine treatment choices., Case Summary: Herein, we report two patients with ESC RCC. Patient 1 was a young woman with classical pathological characteristics. Patient 2 was a 52-year-old man with multifocal metastases, involving the pulmonary hilar and mediastinal lymph nodes, liver, brain, mesosternum, vertebra, rib, femur, and symphysis pubis. Awareness of ESC RCC, along with its characteristic architecture and immunophenotype, would contribute to making a definitive diagnosis, even on core biopsy samples., Conclusion: The discovery of ESC RCC molecular signatures may provide new therapeutic strategies in the future., Competing Interests: Conflict-of-interest statement: The authors declare that they have no conflict of interest to disclose., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Antibody drug conjugate (ADC) therapy has become one of the most promising approaches in cancer immunotherapy. Bispecific targeting could enhance the efficacy and safety of ADC by improving its specificity, affinity and internalization. In this study we constructed a HER2/HER3-targeting bispecific ADC (BsADC) and characterized its physiochemical properties, target specificity and internalization in vitro, and assessed its anti-tumor activities in breast cancer cell lines and in animal models. The HER2/HER3-targeting BsADC had a drug to antibody ratio (DAR) of 2.89, displayed a high selectivity against the target JIMT-1 breast cancer cells in vitro, as well as a slightly higher level of internalization than HER2- or HER3-monospecific ADCs. More importantly, the bispecific ADC potently inhibited the viability of MCF7, JIMT-1, BT474, BxPC-3 and SKOV-3 cancer cells in vitro. In JIMT-1 breast cancer xenograft mice, a single injection of bispecific ADC (3 mg/kg, i.v.) significantly inhibited the tumor growth with an efficacy comparable to that caused by combined injection of HER2 and HER3-monospecific ADCs (3 mg/kg for each). Our study demonstrates that the bispecific ADC concept can be applied to development of more potent new cancer therapeutics than the monospecific ADCs., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

The slow reaction kinetics and severe shuttle effect of lithium polysulfide make Li-S battery electrochemical performance difficult to meet the demands of large electronic devices such as electric vehicles. Based on this, an electrocatalyst constructed by metal phase material (MoS 2 ) and semiconductor phase material (SnS 2 ) with ohmic contact is designed for inhibiting the dissolution of lithium polysulfide with improving the reaction kinetics. According to the density-functional theory calculations, it is found that the heterostructured samples with ohmic contacts can effectively reduce the reaction-free energy of lithium polysulfide to accelerate the sulfur redox reaction, in addition to the excellent electron conduction to reduce the overall activation energy. The metallic sulfide can add more sulfophilic sites to promote the capture of polysulfide. Thanks to the ohmic contact design, the carbon nanotube-MoS 2 -SnS 2 achieved a specific capacity of 1437.2 mAh g -1 at 0.1 C current density and 805.5 mAh g -1 after 500 cycles at 1 C current density and is also tested as a pouch cell, which proves to be valuable for practical applications. This work provides a new idea for designing an advanced and efficient polysulfide catalyst based on ohmic contact., (© 2024 Wiley‐VCH GmbH.)

Background & Aims: Patients with intrahepatic cholangiocarcinoma (iCCA) respond poorly to immune checkpoint blockades (ICBs). In this study, we aimed to dissect the potential mechanisms underlying poor response to ICBs and explore a rational ICB-based combination therapy in iCCA., Methods: scRNA-seq dataset GSE151530 was analyzed to investigate the differentially expressed genes in malignant cells following ICBs therapy. RNA-seq analysis and western blot assays were performed to examine the upstream and downstream signaling pathways of CD73. Subcutaneous tumor xenograft models were utilized to investigate the impact of CD73 on iCCA growth. Plasmid AKT/NICD-induced spontaneous murine iCCAs were used to explore the therapeutic efficacy of CD73 enzymatic inhibitor AB680 combined with PD-1 blockade. Time-of-flight mass cytometry (CyTOF) was conducted to identify the tumor-infiltrating immune cell populations and their functional changes in murine iCCAs treated with AB680 in combination with PD-1 antibody., Results: scRNA-seq analysis identified elevated CD73 expression in malignant cells in response to ICBs therapy. Mechanistically, ICBs therapy upregulated CD73 expression in malignant cells via TNF-α/NF-κB signaling pathway. In vivo studies revealed that CD73 inhibition suppressed the growth of subcutaneous tumors, and achieved synergistic depression effects with gemcitabine and cisplatin (GC). Adenosine produced by CD73 activates AKT/GSK3β/β-catenin signaling axis in iCCA cells. CD73 inhibitor AB680 potentiates anti-tumor efficacy of PD-1 antibody in murine iCCAs. CyTOF analysis showed that AB680 combined with anti-PD-1 therapy promoted the infiltration of CD8 + T, CD4 + T cells, and NK cells in murine iCCAs, while simultaneously decreased the proportions of macrophages and neutrophils. Moreover, AB680 combined with anti-PD-1 significantly upregulated the expression of Granzyme B, Tbet and co-stimulatory molecule ICOS in infiltrating CD8 + T cells., Conclusions: CD73 inhibitor AB680 limits tumor progression and potentiates therapeutic efficacy of GC chemotherapy or anti-PD-1 treatment in iCCA. AB680 combined with anti-PD-1 therapy effectively elicits anti-tumor immune response., (© 2024. The Author(s).)

Background and Aims: Gut microbiota plays a prominent role in the pathogenesis of metabolic dysfunction-associated steatotic liver disease (MASLD). IL-33 is highly expressed at mucosal barrier sites and regulates intestinal homeostasis. Herein, we aimed to investigate the role and mechanism of intestinal IL-33 in MASLD., Approach and Results: In both humans and mice with MASLD, hepatic expression of IL-33 and its receptor suppression of tumorigenicity 2 (ST2) showed no significant change compared to controls, while serum soluble ST2 levels in humans, as well as intestinal IL-33 and ST2 expression in mice were significantly increased in MASLD. Deletion of global or intestinal IL-33 in mice alleviated metabolic disorders, inflammation, and fibrosis associated with MASLD by reducing intestinal barrier permeability and rectifying gut microbiota dysbiosis. Transplantation of gut microbiota from IL-33 deficiency mice prevented MASLD progression in wild-type mice. Moreover, IL-33 deficiency resulted in a decrease in the abundance of trimethylamine N -oxide-producing bacteria. Inhibition of trimethylamine N -oxide synthesis by 3,3-dimethyl-1-butanol mitigated hepatic oxidative stress in mice with MASLD. Nuclear IL-33 bound to hypoxia-inducible factor-1α and suppressed its activation, directly damaging the integrity of the intestinal barrier. Extracellular IL-33 destroyed the balance of intestinal Th1/Th17 and facilitated Th1 differentiation through the ST2- Hif1a - Tbx21 axis. Knockout of ST2 resulted in a diminished MASLD phenotype resembling that observed in IL-33 deficiency mice., Conclusions: Intestinal IL-33 enhanced gut microbiota-derived trimethylamine N -oxide synthesis and aggravated MASLD progression through dual regulation on hypoxia-inducible factor-1α. Targeting IL-33 and its associated microbiota may provide a potential therapeutic strategy for managing MASLD., (Copyright © The Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Neurofibromatosis type 1 (NF 1) is an autosomal-dominant tumor predisposition genetic disease affecting approximately 1 in 3000 live births. The condition could present various manifestations ranging from skin abnormalities to neurological tumors. The musculoskeletal system could also be frequently affected, and scoliosis is the most common orthopedic manifestation. Characterized by the early-onset and rapid progression tendency, NF 1-related dystrophic scoliosis presented discrepancies from idiopathic scoliosis in terms of natural history, clinical features, and management outcomes and thus required special attention. In the current study, the authors conducted a systemic review to outline the body of evidence of the natural history, clinical characteristics, surgical outcomes, and surgical complications of NF 1-induced scoliosis, aiming to provide an elucidative insight into this condition., Method: Systemic review and meta-analysis were conducted according to the latest Preferred Reporting Items for Systematic Reviews Meta-Analyses (PRISMA) guidelines. The search was performed in Medline, Embase, and Web of Science Core Collection up to December 27, 2022, using related keywords. Clinical features such as frequencies, segmental involvement, and hereditary information were summarized and described qualitatively. Meta-analysis was conducted using R software and the 'meta' package to yield an overall outcome of efficacy and safety of surgical management, precisely, spinal fusion procedure and growing rods procedure. Corrective rate of Cobb angle, sagittal kyphosis angle, and T1-S1 length post-operative and at the last follow-up was used to evaluate the efficacy, and the occurrence of surgery-related complications was used to evaluate the safety., Result: A total of 37 articles involving 1023 patients were included. Approximately 26.6% of the NF 1 patients would present with scoliosis. Patients tend to develop scoliosis at an earlier age. The thoracic part turned out to be the most affected segment. No obvious correlation between scoliosis and genotype or hereditary type was observed. Both spinal fusion and growing rod surgery have shown acceptable treatment outcomes, with spinal fusion demonstrating better performance in terms of effectiveness and safety. The growing rods technique seemed to allow a better lengthening of the spine. The mainstay post-operative complications were implant-related complications but could be managed with limited revision surgery. Severe neurological deficits were rarely reported., Conclusion: Scoliosis, especially the subtype characterized by dystrophic bony changes, is a significant orthopedic manifestation of NF1. It has an early onset, a tendency to persistently and rapidly progress, and is challenging to deal with. The current review outlines the available evidence from the perspective of natural history, clinical features, and the treatment efficacy and safety of the mainstay surgical options. Patients with NF1 scoliosis will benefit from a better understanding of the disease and evidence based treatment strategies., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: This study aimed to determine the effectiveness of postoperative adjuvant lenvatinib + PD-1 blockade for patients with early-stage hepatocellular carcinoma (HCC) with microvascular invasion (MVI)., Methods: A total of 393 patients with HCC (Barcelona Clinic Liver Cancer stage 0 or A) who underwent curative hepatectomy with histopathologically proven MVI were enrolled according to the inclusion and exclusion criteria and assigned to 2 groups: surgery alone (surgery-alone group) and surgery with lenvatinib and PD-1 blockade (surgery + lenvatinib + PD-1 group) to compare recurrence-free survival (RFS), overall survival (OS), recurrence type, and annual recurrence rate after the application of propensity score matching (PSM). The Cox proportional hazards model was used for univariate and multivariate analyses., Results: Overall, 99 matched pairs were selected using PSM. Patients in the surgery + lenvatinib + PD-1 group had significantly higher 3-year RFS rates (76.8%, 65.7%, and 53.5%) than patients in the surgery-alone group (60.6%, 45.5%, and 37.4%) (P = .012). The 2 groups showed no significant difference in recurrence types and OS. Surgery alone, MVI-M2, and alpha-fetoprotein of ≥200 ng/mL were independent risk factors for RFS (P < .05), and history of alcohol use disorder was an independent risk factor for OS (P = .022)., Conclusion: Postoperative lenvatinib + PD-1 blockade improved the RFS in patients with HCC with MVI and was particularly beneficial for specific individuals., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

We reported a chiral oxamide-phosphine ligand (COAP-Ph)-Pd-catalyzed asymmetric [3+2] cycloaddition reaction between vinyl cyclopropane compounds derived from 1,3-indanedione and 2-vinylcyclopropane-1,1-dicarboxylates with cyclic sulfonyl 1-azadienes. The corresponding reactions provided a series of enantiomerically active spiro cyclopentane-indandione and cyclopentane structures bearing three consecutive stereogenic centers in good yields with good diastereo- and enantioselectivity. The COAP-Pd complex serves not only to promote generation of chiral π-allyl-palladium intermediates and induce the asymmetry of the reaction, but also depress the background reaction., (© 2024 Wiley-VCH GmbH.)

T cell engaging bispecific antibodies (TCBs) have recently become significant in cancer treatment. In this study we developed MSLN490, a novel TCB designed to target mesothelin (MSLN), a glycosylphosphatidylinositol (GPI)-linked glycoprotein highly expressed in various cancers, and evaluated its efficacy against solid tumors. CDR walking and phage display techniques were used to improve affinity of the parental antibody M912, resulting in a pool of antibodies with different affinities to MSLN. From this pool, various bispecific antibodies (BsAbs) were assembled. Notably, MSLN490 with its IgG-[L]-scFv structure displayed remarkable anti-tumor activity against MSLN-expressing tumors (EC 50 : 0.16 pM in HT-29-hMSLN cells). Furthermore, MSLN490 remained effective even in the presence of non-membrane-anchored MSLN (soluble MSLN). Moreover, the anti-tumor activity of MSLN490 was enhanced when combined with either Atezolizumab or TAA × CD28 BsAbs. Notably, a synergistic effect was observed between MSLN490 and paclitaxel, as paclitaxel disrupted the immunosuppressive microenvironment within solid tumors, enhancing immune cells infiltration and improved anti-tumor efficacy. Overall, MSLN490 exhibits robust anti-tumor activity, resilience to soluble MSLN interference, and enhanced anti-tumor effects when combined with other therapies, offering a promising future for the treatment of a variety of solid tumors. This study provides a strong foundation for further exploration of MSLN490's clinical potential., (© 2024. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Phosphate-based electrolyte propels the advanced battery system with high safety. Unfortunately, restricted by poor electrochemical stability, it is difficult to be compatible with advanced lithium metal anodes and Ni-rich cathodes. To alleviate these issues, the study has developed a phosphate-based localized high-concentration electrolyte with a nitrate-driven solvation structure, and the nitrate-derived N-rich inorganic interface shows excellent performance in stabilizing the LiNi 0.8 Co 0.1 Mn 0.1 O 2 (NCM811) cathode interface and modulating the lithium deposition morphology on the anode. The results show that the Li|| NCM811 cell has exceptional long-cycle stability of >80% capacity retention after 800 cycles at 4.3 V, 1 C. A more prominent capacity retention rate of 93.3% after 200 cycles can be reached with the high voltage of 4.5 V. While being compatible with the phosphate-based electrolyte with good flame retardancy and the good electrochemical stability of Ni-rich lithium metal battery (LMBs) systems, the present work expands the construction of anion-rich solvation structures, which is expected to promote the development of the high-performance LMBs with safety., (© 2024 Wiley‐VCH GmbH.)

Background: Anatomical sectionectomy based on Takasaki's segmentation has shown advantages in hepatocellular carcinoma. However, whether this approach improves the survival of intrahepatic cholangiocarcinoma (ICC) remains unknown., Methods: A series of 248 consecutive patients with solitary ICCs who underwent hepatectomy were studied retrospectively. The patients were classified into the groups of anatomical sectionectomy based on Takasaki's segmentation (TS group) and non-Takasaki's hepatectomy (NTH group). The bias between the two groups was minimized using propensity score matching (PSM). Recurrence-free survival (RFS) and overall survival (OS) were evaluated with Kaplan-Meier analysis. The Cox proportional hazards model was performed to determine the adverse risk factors associated with survival., Results: After PSM, 67 pairs of patients were compared. Both the RFS and OS rates in the TS group were significantly better than those in the NTH group (23.2 % vs. 16.5 %, and 40.4 % vs. 27.3 %, P = 0.035 and 0.032, respectively). Multivariate analysis showed that NTH was independently associated with worse RFS and OS than TS. The stratified analysis demonstrated that the RFS and OS rates in the TS group with tumor stage I and tumor size ≥3 cm were significantly better than those in the NTH group, while the survival rates for ICC with stage I and tumor size <3 cm or stage II-III showed no significant difference., Conclusion: TS was associated with improved RFS and OS in patients with solitary ICC even after PSM. TS may be preferred particularly in patients with tumor stage I and tumor size ≥3 cm., (Copyright © 2024. Published by Elsevier Ltd.)

The localized high-concentration electrolyte (LHCE) propels the advanced high-voltage battery system. Sulfone-based LHCE is a transformative direction compatible with high energy density and high safety. In this work, the application of lithium bis(trifluoromethanesulphonyl)imide and lithium bis(fluorosulfonyl)imide (LiFSI) in the LHCE system constructed from sulfolane and 1,1,2,2-tetrafluoroethyl-2,2,3,3-tetrafluoropropyl ether (TTE) is investigated. The addition of diluent causes an increase of contact ion pairs and ionic aggregates in the solvation cluster and an acceptable quantity of free solvent molecules. A small amount of LiFSI as an additive can synergistically decompose with TTE on the cathode and participate in the construction of both electrode interfaces. The designed electrolyte helps the Ni-rich system to cycle firmly at a high voltage of 4.5 V. Even with high mass load and lean electrolyte, it can keep a reversible specific capacity of 91.5% after 50 cycles. The constructed sulfone-based electrolyte system exhibits excellent thermal stability far beyond the commercial electrolytes. Further exploration of in-situ gelation has led to a quick conversion of the designed liquid electrolyte to the gel state, accompanied by preserved stability, which provides a direction for the synergistic development of LHCE with gel electrolytes., (© 2024 Wiley‐VCH GmbH.)

Background: Chromobox Homolog 1 (CBX1) plays a crucial role in the pathogenesis of numerous diseases, including the evolution and advancement of diverse cancers. The role of CBX1 in pan-cancer and its mechanism in hepatocellular carcinoma (HCC), however, remains to be further investigated., Methods: Bioinformatics approaches were harnessed to scrutinize CBX1's expression profile, its association with tumor staging, and its potential impact on patient outcomes across various cancers. Single-cell RNA sequencing data facilitated the investigation of CBX1 expression patterns at the individual cell level. The CBX1 expression levels in HCC and adjacent non-tumor tissues were quantified through Real-Time Polymerase Chain Reaction (RT-PCR), Western Blotting (WB), and Immunohistochemical analyses. A tissue microarray was employed to explore the relationship between CBX1 levels, patient prognosis, and clinicopathological characteristics in HCC. Various in vitro assays-including CCK-8, colony formation, Transwell invasion, and scratch tests-were conducted to assess the proliferative and motility properties of HCC cells upon modulation of CBX1 expression. Moreover, the functional impact of CBX1 on HCC was further discerned through xenograft studies in nude mice., Results: CBX1 was found to be upregulated in most cancer forms, with heightened expression correlating with adverse patient prognoses. Within the context of HCC, elevated levels of CBX1 were consistently indicative of poorer clinical outcomes. Suppression of CBX1 through knockdown methodologies markedly diminished HCC cell proliferation, invasive capabilities, migratory activity, Epithelial-mesenchymal transition (EMT) processes, and resistance to Tyrosine kinase inhibitors (TKIs). Contrastingly, CBX1 augmentation facilitated the opposite effects. Subsequent investigative efforts revealed CBX1 to be a promoter of EMT and a contributor to increased TKI resistance within HCC cells, mediated via the IGF-1R/AKT/SNAIL signaling axis. The oncogenic activities of CBX1 proved to be attenuable either by AKT pathway inhibition or by targeted silencing of IGF-1R., Conclusions: The broad overexpression of CBX1 in pan-cancer and specifically in HCC positions it as a putative oncogenic entity. It is implicated in forwarding HCC progression and exacerbating TKI resistance through its interaction with the IGF-1R/AKT/SNAIL signaling cascade., (© 2024. The Author(s).)

Objective: Periventricular-intraventricular hemorrhage is the most common type of intracranial bleeding in newborns, especially in the first 3 days after birth. Severe periventricular-intraventricular hemorrhage is considered a progression from mild periventricular-intraventricular hemorrhage and is often closely associated with severe neurological sequelae. However, no specific indicators are available to predict the progression from mild to severe periventricular-intraventricular in early admission. This study aims to establish an early diagnostic prediction model for severe PIVH., Method: This study was a retrospective cohort study with data collected from the MIMIC-III (v1.4) database. Laboratory and clinical data collected within the first 24 h of NICU admission have been used as variables for both univariate and multivariate logistic regression analyses to construct a nomogram-based early prediction model for severe periventricular-intraventricular hemorrhage and subsequently validated., Results: A predictive model was established and represented by a nomogram, it comprised three variables: output, lowest platelet count and use of vasoactive drugs within 24 h of NICU admission. The model's predictive performance showed by the calculated area under the curve was 0.792, indicating good discriminatory power. The calibration plot demonstrated good calibration between observed and predicted outcomes, and the Hosmer-Lemeshow test showed high consistency (p = 0.990). Internal validation showed the calculated area under a curve of 0.788., Conclusions: This severe PIVH predictive model, established by three easily obtainable indicators within the NICU, demonstrated good predictive ability. It offered a more user-friendly and convenient option for neonatologists., Competing Interests: Conflicts of interest The authors declare no conflicts of interest., (Copyright © 2024 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. All rights reserved.)

An alpha-proteobacterial strain JXJ CY 53  T was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) collected from Lake Dianchi, China. JXJ CY 53  T was observed to be an aerobic, Gram-stain-negative, oval shaped, and mucus-secreting bacterium. It had C 18:1 ω7c and C 16:0 as the major cellular fatty acids, Q-10 as the predominant ubiquinone, and sphingoglycolipid, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylmethylethanolamine as the polar lipids. The G + C content of DNA was 65.85%. The bacterium had 16S rRNA gene sequence identities of 98.9% and 98.7% with Sphingomonas panni DSM 15761  T and Sphingomonas hankookensis KCTC 22579  T , respectively, while less than 97.4% identities with other members of the genus. Further taxonomic analysis indicated that JXJ CY 53  T represented a new member of Sphingomonas, and the species epithet was proposed as Sphingomonas lacusdianchii sp. nov. (type strain JXJ CY 53  T  = KCTC 72813  T  = CGMCC 1.17657  T ). JXJ CY 53  T promoted the growth of MF-905 by providing bio-available phosphorus and nitrogen, plant hormones, vitamins, and carotenoids. It could modulate the relative abundances of nonculturable bacteria associated with MF-905 and influence the interactions of MF-905 and other bacteria isolated from the cyanobacterium, in addition to microcystin production characteristics. Meanwhile, MF-905 could provide JXJ CY 53  T dissolved organic carbon for growth, and control the growth of JXJ CY 53  T by secreting specific chemicals other than microcystins. Overall, these results suggest that the interactions between Microcystis and its attached bacteria are complex and dynamic, and may influence the growth characteristics of the cyanobacterium. This study provided new ideas to understand the interactions between Microcystis and its attached bacteria. KEY POINTS: • A novel bacterium (JXJCY 53 T ) was isolated from the cyanosphere of Microcystis sp. FACHB-905 (MF-905) • JXJCY 53 T modulated the growth and microcystin production of MF-905 • MF-905 could control the attached bacteria by specific chemicals other than microcystins (MCs)., (© 2024. The Author(s).)

Background: Adequate evaluation of degrees of liver cirrhosis is essential in surgical treatment of hepatocellular carcinoma (HCC) patients. The impact of the degrees of cirrhosis on prediction of post-hepatectomy liver failure (PHLF) remains poorly defined. This study aimed to construct and validate a combined pre- and intra-operative nomogram based on the degrees of cirrhosis in predicting PHLF in HCC patients using prospective multi-center's data., Methods: Consecutive HCC patients who underwent hepatectomy between May 18, 2019 and Dec 19, 2020 were enrolled at five tertiary hospitals. Preoperative cirrhotic severity scoring (CSS) and intra-operative direct liver stiffness measurement (DSM) were performed to correlate with the Laennec histopathological grading system. The performances of the pre-operative nomogram and combined pre- and intra-operative nomogram in predicting PHLF were compared with conventional predictive models of PHLF., Results: For 327 patients in this study, histopathological studies showed the rates of HCC patients with no, mild, moderate, and severe cirrhosis were 41.9%, 29.1%, 22.9%, and 6.1%, respectively. Either CSS or DSM was closely correlated with histopathological stages of cirrhosis. Thirty-three (10.1%) patients developed PHLF. The 30- and 90-day mortality rates were 0.9%. Multivariate regression analysis showed four pre-operative variables [HBV-DNA level, ICG-R15, prothrombin time (PT), and CSS], and one intra-operative variable (DSM) to be independent risk factors of PHLF. The pre-operative nomogram was constructed based on these four pre-operative variables together with total bilirubin. The combined pre- and intra-operative nomogram was constructed by adding the intra-operative DSM. The pre-operative nomogram was better than the conventional models in predicting PHLF. The prediction was further improved with the combined pre- and intra-operative nomogram., Conclusions: The combined pre- and intra-operative nomogram further improved prediction of PHLF when compared with the pre-operative nomogram., Trial Registration: Clinicaltrials.gov Identifier: NCT04076631., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://hbsn.amegroups.com/article/view/10.21037/hbsn-22-410/coif). The authors have no conflicts of interest to declare., (2024 Hepatobiliary Surgery and Nutrition. All rights reserved.)

Soil microplastics (MPs) have attracted widespread attention recently. Most studies have explored how soil MPs affect the soil's physicochemical parameters, matter circulation, and soil microbial community assembly. Similarly, a key concern in agricultural development has been the use of phosphorus (P) fertiliser, which is essential for plant health and development. However, the relationship between MPs and phosphate fertilisers and their effects on the soil environment and plant growth remains elusive. This study assessed the influence of adding low-density polyethylene MPs (1%) with different phosphate fertiliser application rates on microbial communities and rice biomass. Our results showed that MPs changed the structure of soil bacterial and phoD-harbouring microbial communities in the treatment with P fertiliser at the same level and suppressed the interactions of phoD-harbouring microorganisms. In addition, we found that MPs contamination inhibited rice growth; however, the inclusion of P fertiliser in MP-contaminated soils reduced the inhibitory action of MPs on rice growth, probably because the presence with P fertiliser promoted the uptake of NO 3 - -N by rice in MP-contaminated soils. Our results provide further insights into guiding agricultural production, improving agricultural management, and rationally applying phosphate fertilisers in the context of widespread MPs pollution and global P resource constraints., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: Diarrhea is a common complication of hematopoietic stem cell transplantation (HSCT) and is associated with substantial morbidity, but its etiology is often unknown. Etiologies of diarrhea in this population include infectious causes, chemotherapy- or medication-induced mucosal injury and graft-versus-host disease (GVHD). Distinguishing these potential causes of diarrhea is challenging since diarrheal symptoms are often multifactorial, and the etiologies often overlap in transplant patients. The objectives of this study were to evaluate whether the FilmArray gastrointestinal (GI) panel would increase diagnostic yield and the degree to which pre-transplantation colonization predicts post-transplantation infection., Methods: From November 2019 to February 2021, a total of 158 patients undergoing HSCT were prospectively included in the study. Stool specimens were obtained from all HSCT recipients prior to conditioning therapy, 28 ± 7 days after transplantation and at any new episode of diarrhea. All stool samples were tested by the FilmArray GI panel and other clinical microbiological assays., Results: The primary cause of post-transplantation diarrhea was infection (57/84, 67.86%), followed by medication (38/84, 45.24%) and GVHD (21/84, 25.00%). Ninety-five of 158 patients were colonized with at least one gastrointestinal pathogen before conditioning therapy, and the incidence of infectious diarrhea was significantly higher in colonized patients (47/95, 49.47%) than in non-colonized patients (10/63, 15.87%) (P < 0.001). Fourteen of 19 (73.68%) patients who were initially colonized with norovirus pre-transplantation developed a post-transplantation norovirus infection. Twenty-four of 62 (38.71%) patients colonized with Clostridium difficile developed a diarrheal infection. In addition, FilmArray GI panel testing improved the diagnostic yield by almost twofold in our study (55/92, 59.78% vs. 30/92, 32.61%)., Conclusions: Our data show that more than half of pediatric patients who were admitted for HSCT were colonized with various gastrointestinal pathogens, and more than one-third of these pathogens were associated with post-transplantation diarrhea. In addition, the FilmArray GI panel can increase the detection rate of diarrheal pathogens in pediatric HSCT patients, but the panel needs to be optimized for pathogen species, and further studies assessing its clinical impact and cost-effectiveness in this specific patient population are also needed., (© 2024. The Authors.)

Based on air quality monitoring, surface meteorological data, wind profile radar observation, and the HYSPLIT model, the characteristics and causes of O 3 pollution in eastern China during the period of the typhoons BAVI, MAYSAK, and HAISHEN from August 26 to September 8, 2020 were analyzed. The results showed that during the succession of the three landfall typhoons, the O 3 pollution sites in Beijing Tianjin Hebei and its surrounding areas (BTHS) and the Yangtze River Delta (YRD) exceeded 50%. During the HAISHEN period, O 3 pollution days in the two regions reached 2.22 d and 2.97 d, respectively, with significant persistence characteristics. The location of the typhoon had an obvious influence on O 3 concentration. When the typhoons were located within the 24h warning line, the O 3 concentrations in BTHS and YRD were relatively low. When the typhoons were located between the 24 h and 48 h warning lines, the O 3 concentration in BTHS was the highest. When the typhoons moved north of 34°N, the YRD was most prone to regional O 3 pollution. O 3 pollution in Shanghai mainly occurred under the control of the northward air flow to the west side of the typhoons, and the regional transport from the upstream area had a significant impact on the increase in O 3 and its precursor concentrations. The downdraft below 1 000 m maintained O 3 at a high concentration at night. In Jinan, O 3 pollution mainly occurred under the control of the subtropical high and typhoon periphery. The downdraft prevailed in the middle and lower levels during the O 3 pollution. From August 28 to 30, under the control of the subtropical high, the pollutants were mainly accumulated locally, and some of them were transmitted within the province, showing a "double high" phenomenon of O 3 and PM 2.5 . From September 5 to 8, under the influence of HAISHEN peripheral circulation, the regional transport was obvious, and the O 3 concentration increased earlier than that of PM 2.5 .

A novel alphaproteobacterial strain JXJ CY 41 T was isolated from a culture mass of Microcystis, collected from Lake Dianchi, south-west, China. Strain JXJ CY 41 T was gram-strain-negative, aerobic, motile, with rod-shaped cells (0.4-1.0 × 1.7-3.5 μm). It was positive for catalase and starch hydrolysis, negative for oxidase and hydrolysis of Tweens (20, 40, and 80). Growth occurred at 10-44 °C, pH 5.0-10.0, and 0-5.0% (w/v) NaCl. Major fatty acids included C 16:0 (28.1%), 11-methyl C 18:1 ω7c (36.7%) and C 18:1 ω7c (20.8%). Q10 was the sole ubiquinone. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, glycolipid, and an unidentified lipid. The DNA G + C content was 63.1%. Its 16S rRNA gene sequence showed high similarities with Devosia oryziradicis G19 T (99.5%; not validly published), D. yakushimensis Yak96B T (98.3%) and D. ginsengisoli Gsoil 520 T (98.1%), and less than 98.1% similarities with other members of the genus Devosia. The digital DNA-DNA hybridization (dDDH) and average nucleotide identity (ANI) values between strain JXJ CY 41 T and its 5 closest similar strains were 19.9-24.1% and 75.7-80.5%, respectively. Based on the data above, strain JXJ CY 41 T was identified as a novel species of the genus Devosia, for which the epithet Devosia lacusdianchii sp. nov. was proposed. The type strain is JXJ CY 41 T (= KCTC 72812 T  = CGMCC 1.17502 T ). Strain JXJ CY 41 T exhibited different interactions with Microcystis aeruginosa FACHB-905 (Maf) under different conditions, and Maf could control the bacterial cellular density by secreting unknown specific chemical compounds according to its nutritional requirements., (© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Solid-state batteries have become the most anticipated option for compatibility with high-energy density and safety. In situ polymerization, a novel strategy for the construction of solid-state systems, has extended its application from solid polymer electrolyte systems to other solid-state systems. This review summarizes the application of in situ polymerization strategies in solid-state batteries, which covers the construction of polymer, the formation of the electrolyte system, and the design of the full cell. For the polymer skeleton, multiple components and structures are being chosen. In the construction of solid polymer electrolyte systems, the choice of initiator for in situ polymerization is the focus of this review. New initiators, represented by lithium salts and additives, are the preferred choice because of their ability to play more diverse roles, while the coordination with other components can also improve the electrical properties of the system and introduce functionalities. In the construction of entire solid-state battery systems, the application of in situ polymerization to structure construction, interface construction, and the use of separators with multiplex functions has brought more possibilities for the development of various solid-state systems and even the perpetuation of liquid electrolytes., (© 2023 Wiley-VCH GmbH.)

Objective: Numerous schizophrenic patients are suffering from obesity primarily attributed to antipsychotic medication and poor dietary habits. This study investigated the progressive deterioration of olanzapine-induced metabolic disorders in the presence of a high-fat diet (HFD) and explored the involvement of endoplasmic reticulum (ER) stress., Methods: Female Sprague-Dawley rats fed on a standard chow diet or HFD were treated with olanzapine (3 mg/kg/day) and the ER stress inhibitor 4-phenylbutyric acid (4-PBA, 1 and 0.5 g/kg/day) for 8 days. Changes in body weight, food intake, and plasma lipids were assessed. Hepatic fat accumulation was evaluated using oil red O staining. Western blotting and immunofluorescence assays were employed to examine the expression of ER stress markers, NOD-like receptor pyrin domain-containing protein 3 (NLRP3), and proopiomelanocortin (POMC) in the hypothalamus or liver., Results: Compared to olanzapine alone, olanzapine+HFD induced greater weight gain, increased hyperlipidemia, and enhanced hepatic fat accumulation (P<0.05). Co-treatment with 4-PBA exhibited a dose-dependent inhibition of these effects (P<0.05). Further mechanistic investigations revealed that olanzapine alone activated ER stress, upregulated NLRP3 expression in the hypothalamus and liver, and downregulated hypothalamic POMC expression. The HFD exacerbated these effects by 50%-100%. Moreover, co-administration of 4-PBA dose-dependently attenuated the olanzapine+HFD-induced alterations in ER stress, NLRP3, and POMC expression in the hypothalamus and liver (P<0.05)., Conclusion: HFD worsened olanzapine-induced weight gain and lipid metabolic disorders, possibly through ER stress-POMC and ER stress-NLRP3 signaling. ER stress inhibitors could be effective in preventing olanzapine+HFD-induced metabolic disorders., (© 2023. Huazhong University of Science and Technology.)

Biochar as an agricultural soil amendment plays vital roles in mediating methane (CH 4 ) and nitrous oxide (N 2 O) emissions in soils. The link between different types of biochar, bulk soil, and rhizosphere microbial communities in relation to CH 4 and N 2 O emissions is being investigated in this study. The rice pot experiment was conducted using biochar at two temperatures (300°C and 500°C) in combination with three biochar levels (0, 2, 10% w/w). Soil properties and the abundance of genes associated with CH 4 and N 2 O emissions from both rhizosphere and bulk soils were investigated. The study also aimed to examine the structure of microbial communities ( pmoA , nosZ ) in rhizosphere and bulk soils whereas CH 4 and N 2 O emissions were monitored while growing rice. Results showed that biochar at 300°C and 10% incorporation significantly increased the CH 4 emissions by up to 59% rise compared to the control group. Random Forest analysis revealed that the ratio of mcrA/pmoA along with the abundance of mcrA from both rhizosphere and bulk soils, the abundance of AOA , TN, DOC, and the community composition of pmoA -harboring microorganisms from both bulk and rhizosphere soils were important predictors of CH 4 emissions. Therefore, the ratio of mcrA/pmoA in rhizosphere soil and the abundance of AOA in bulk soil were the main factors influencing CH 4 emissions. Variation Partitioning Analysis (VPA) results indicated that the effects of these factors on bulk soil were 9% of CH 4 emissions variations in different treatments, which contributed more than rhizosphere soils' factors. Moreover, random forest analysis results indicated that the abundance of AOB in bulk soil was the most important predictor influencing N 2 O emissions. The VPA result revealed that the factors in rhizosphere soil could explain more than 28% of the variations in N 2 O emissions. Our study highlights that rhizosphere soil has a more significant effect than bulk soil on N 2 O production. Our findings further the understanding of the link between bulk and rhizosphere attributes, and their impact on CH 4 and N 2 O emissions in paddy soils. In summary, we recommend the application of biochar at 500°C and 2% incorporation rate for agricultural production in the area., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Qi, Yuan, Zhuang, Zama, Tian, Tao and Zhang.)

Objective: This study aims to investigate the proportion and distribution of female HPB surgeons in China, describe their current status, and analyze the possible barriers and challenges in their careers., Method: Tertiary hospitals with the division of HPB in mainland China in 2021 were enrolled and surgeon demographic information was collected through the review of official websites and/or telephone interviews., Results: The majority of female HPB surgeons (72.92%) were located in the first or second-tier cities in mainland China, with an increasing number of new female HPB surgeons entering the field annually, particularly after 2005 (from 27 to 52 per 5 years). Despite no significant difference in academic backgrounds, female HPB surgeons initiated their careers at an earlier age and took a longer time to obtain chief titles (P < 0.05). Interestingly, female HPB surgeons performed laparoscopic complex HPB cases at a similar rate (95.42%) to their male counterparts and were more likely to specialize in endoscopic surgery (P = 0.021), with a similar ratio of obtaining administrative positions., Conclusion: Minimally invasive surgery may provide females with unprecedented opportunities in the HPB surgery field. However, despite the increasing numbers of female HPB surgeons, the proportion remains low in China., (Copyright © 2023 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Background: To develop a radiomics model based on chest computed tomography (CT) for the prediction of a pathological complete response (pCR) after neoadjuvant or conversion chemoimmunotherapy (CIT) in patients with non-small cell lung cancer (NSCLC)., Methods: Patients with stage IB-III NSCLC who received neoadjuvant or conversion CIT between September 2019 and July 2021 at Hunan Cancer Hospital, Xiangya Hospital, and Union Hospital were retrospectively collected. The least absolute shrinkage and selection operator (LASSO) were used to screen features. Then, model 1 (five radiomics features before CIT), model 2 (four radiomics features after CIT and before surgery) and model 3 were constructed for the prediction of pCR. Model 3 included all nine features of model 1 and 2 and was later named the neoadjuvant chemoimmunotherapy-related pathological response prediction model (NACIP)., Results: This study included 110 patients: 77 in the training set and 33 in the validation set. Thirty-nine (35.5%) patients achieved a pCR. Model 1 showed area under the curve (AUC) = 0.65, 64% accuracy, 71% specificity, and 50% sensitivity, while model 2 displayed AUC = 0.81, 73% accuracy, 62% specificity, and 92% sensitivity. In comparison, NACIP yielded a good predictive value, with an AUC of 0.85, 81% accuracy, 81% specificity, and 83% sensitivity in the validation set., Conclusion: NACIP may be a potential model for the early prediction of pCR in patients with NSCLC treated with neoadjuvant/conversion CIT., (© 2023 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd.)

Objectives: This meta-analysis aims to evaluate the effect of n-3 polyunsaturated fatty acids (PUFAs) as a part of parenteral nutrition in patients undergoing liver surgery., Design: Systematic review and meta-analysis., Data Sources: PubMed, the Cochrane Central Register of Controlled Trials, Springer link, Web of Science, China National Knowledge Infrastructure and VIP Database., Eligibility Criteria: We included randomised controlled trials (RCTs) and evaluated the outcomes of liver function, inflammatory reaction, the influence of certain markers of the immune system, and specific clinical indexes for patients undergoing liver surgery and receiving parenteral nutrition with n-3 PUFAs., Data Extraction and Synthesis: The Cochrane Collaboration's tool was used to assess the risk of bias for each study. Findings were summarised in Grades of Recommendation, Assessment, Development and Evaluation evidence profiles and synthesised qualitatively., Results: Eight RCTs, including 748 patients (trial: 374; control: 374), were included in the meta-analysis. Compared with patients in the control group, the patients in the n-3 PUFA group who underwent liver surgery had significantly lower aspartate aminotransferase (mean difference, MD -42.72 (95% CI -71.91 to -13.52); p=0.004), alanine aminotransferase (MD -38.90 (95% CI -65.44 to -12.37); p=0.004), white cell count (MD -0.93 (95% CI -1.60 to -0.26); p=0.007) and IL-6 (MD -11.37 (95% CI -14.62 to -8.13); p<0.00001) levels and a higher albumin level (MD 0.42 (95% CI 0.26 to 0.57); p<0.00001). They also had fewer infection complications (OR 0.44 (95% CI 0.28 to 0.68); p=0.0003) and a shorter duration of hospital stay (MD -2.17 (95% CI -3.04 to -1.3); p<0.00001) than the controls. However, there were no significant differences in terms of total bilirubin, TNF-α, IL-2, IgA, IgG, IgM and CD3, biliary leakage and mortality between the two groups., Conclusions: We found that n-3 PUFAs can benefit patients undergoing liver surgery by improving liver function and certain clinical indexes and decreasing related inflammation factors. However, there are limited RCTs on the application of n-3 PUFAs for patients undergoing liver surgery. Further evidence of the benefit of n-3 PUFAs in these patients warrants further exploration., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Alpha-synuclein ( SNCA ) copy number variations (CNV) have been certified as a causative mutation in patients with familial and sporadic Parkinson's disease (PD)., Case: We report three SNCA duplication cases diagnosed as PD. Through whole-exome sequencing, we identified a de novo 4.56 Mb repeated region in one patient and a 2.50 Mb repeated region in familial PD with two patients., Literature Review: In review of previous cases, we suggest that aggressive behavior is more remarkable in CNV4 patients. Meanwhile, frequency of cognition decline and dementia were slightly increased in CNV4 patients. We also illustrate a younger onset age in offspring than parent in familial SNCA multiplication PD cases. No difference was observed in disease duration between parent and offspring generation., Conclusions: Our findings demonstrated the clinical and genetic characteristics in PD with SNCA multiplication and provided strong evidence for genetic anticipation. These results may be instructive for future disease diagnosis and genetic counseling., (© 2023 International Parkinson and Movement Disorder Society.)

Uroteuthis edulis , an important fishery target species, plays an important role in the food web of the East China Sea. We collected U. edulis samples in the East China Sea from September 2020 to January 2021 to examine their feeding differences in autumn and winter based on fatty acid and stable isotope analyses. The results showed that the content of polyunsaturated fatty acids (PUFA) was the highest, followed by saturated fatty acids (SFA), and the lowest content of monounsaturated fatty acids (MUFA) in autumn and winter. Results of the similarity ana-lysis showed significant differences in PUFA and MUFA contents but no differences in SFA contents between autumn and winter. Results of non-metric multidimensional scale analysis showed that C18:1n9 could be used as signature fatty acids in autumn samples and C22:6n3 as characteristic fatty acids in winter samples. There was significant difference of δ 15 N between autumn and winter, but no difference of δ 13 C. The total area (TA), range of δ 15 N (NR), standard ellipse area (SEA) and the corrected version of the standard ellipse area (SEA C ) in autumn were all smaller than those in winter, but range of δ 13 C (CR) was on the contrary. Results of the Spearman rank correlation test showed that there were differences between fatty acid content and stable isotope ratio of U. edulis and the dorsal mantle length in autumn and winter. Our results could provide basic data for understanding material and energy flow of the East China Sea food web, which is conducive to the sustainable development and utilization of U. edulis.

The single-nucleotide polymorphism (SNP) rs2235371 ( IRF6 V274I) is associated with nonsyndromic cleft lip with or without cleft palate (NSCL/P) in Han Chinese and other populations but appears to be without a functional effect. To find the common etiologic variant or variants within the haplotype tagged by rs2235371, we carried out targeted sequencing of an interval containing IRF6 in 159 Han Chinese with NSCL/P. This study revealed that the SNP rs12403599, within the IRF6 promoter, is associated with all phenotypes of NSCL/P, especially nonsyndromic cleft lip (NSCLO) and a subphenotype of it, microform cleft lip (MCL). This association was replicated in 2 additional much larger cohorts of cases and controls from the Han Chinese. Conditional logistic analysis indicated that association of rs2235371 with NSCL/P was lost if rs12403599 was excluded. rs12403599 contributes the most risk to MCL: its G allele is responsible for 38.47% of the genetic contribution to MCL, and the odds ratios of G/C and G/G genotypes were 2.91 and 6.58, respectively, for MCL. To test if rs12403599 is functional, we carried out reporter assays in a fetal oral epithelium cells (GMSM-K). Unexpectedly, the risk allele G yielded higher promoter activity in GMSM-K. Consistent with the reporter studies, expression of IRF6 in lip tissues from NSCLO and MCL patients with the G/G phenotype was higher than in those from patients with the C/C phenotype. These results indicate that rs12403599 is tagging the risk haplotype for NSCL/P better than rs2235371 in Han Chinese and supports investigation of the mechanisms by which the allele of rs12403599 affects IRF6 expression and tests of this association in different populations.

The continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants poses challenges to the effectiveness of neutralizing antibodies. Rational design of antibody cocktails is a realizable approach addressing viral immune evasion. However, evaluating the breadth of antibody cocktails is essential for understanding the development potential. Here, based on a replication competent vesicular stomatitis virus model that incorporates the spike of SARS-CoV-2 (VSV-SARS-CoV-2), we evaluated the breadth of a number of antibody cocktails consisting of monoclonal antibodies and bispecific antibodies by long-term passaging the virus in the presence of the cocktails. Results from over two-month passaging of the virus showed that 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 from these cocktails were highly resistant to random mutation, and there was no breakthrough after 30 rounds of passaging. As a control, antibody REGN10933 was broken through in the third passage. Next generation sequencing was performed and several critical mutations related to viral evasion were identified. These mutations caused a decrease in neutralization efficiency, but the reduced replication rate and ACE2 susceptibility of the mutant virus suggested that they might not have the potential to become epidemic strains. The 9E12 + 10D4 + 2G1 and 7B9-9D11 + 2G1 cocktails that picked from the VSV-SARS-CoV-2 system efficiently neutralized all current variants of concern and variants of interest including the most recent variants Delta and Omicron, as well as SARS-CoV-1. Our results highlight the feasibility of using the VSV-SARS-CoV-2 system to develop SARS-CoV-2 antibody cocktails and provide a reference for the clinical selection of therapeutic strategies to address the mutational escape of SARS-CoV-2., (© 2023. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Bone mesenchymal stem cell-derived exosome (BMSC-exosome) is a potential candidate for lung ischemia-reperfusion injury (LIRI) treatment. This study aims to investigate the anti-pyroptosis effect of BMSC-exosomes in LIRI. The LIRI cell model was established by hypoxia/reoxygenation (H/R) treatment. Interleukin (IL)-1β and IL-18 levels were examined by enzyme-linked immunosorbent assay. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide assay. Lactate dehydrogenase (LDH) release was examined using a LDH assay kit. The interaction between microRNA (miR)-202-5p and cytidine monophosphate kinase 2 (CMPK2) was analyzed using dual-luciferase reporter assay and RNA immunoprecipitation. BMSC-exosomes promoted cell viability and suppressed pyroptosis in H/R-treated mouse lung epithelial. miR-202-5p was enriched in BMSC-exosomes, and exosomal miR-202-5p inhibition upregulated pyroptosis-associated proteins, including cleaved N-terminal Gasdermin D, nucleotide-binding domain-like receptor family member pyrin domain-containing protein 3, and Caspase1. Meanwhile, miR-202-5p suppressed CMPK2 expression by directly targeting CMPK2. Expectedly, CMPK2 knockdown reversed the promoting effect of exosomal miR-202-5p inhibition on pyroptosis in LIRI. Therefore, BMSC-derived exosome miR-202-5p repressed pyroptosis to inhibit LIRI progression by targeting CMPK2., (© 2023 The Authors. The Kaohsiung Journal of Medical Sciences published by John Wiley & Sons Australia, Ltd on behalf of Kaohsiung Medical University.)

Based on the concentration data of seven heavy metal elements[As, Cd, Cu, Pb, Hg, Ni, and Cr(Ⅵ)] in the surface soil of a typical industrial park in northwest China, the characteristics of heavy metal pollution in the industrial park were analyzed, and the ecological risk and pollution were evaluated using the potential ecological risk index and the index of geo-accumulation. The positive matrix factorization (PMF) model and random forest (RF) model were used for quantitative source analysis, and the emission data of sampling enterprises and empirical data of the source emission component spectrum were combined to identify the characteristic elements and determine the emission source category. The results showed that the heavy metals at all sampling points in the park did not exceed the second-class screening value of construction land in the soil pollution risk control standard for construction land (GB 36600-2018). However, compared with the local soil background values, five elements, excluding As and Cr, were enriched in different degrees, presenting slight pollution and moderate ecological risk (RI=250.04). Cd and Hg were the main risk elements of the park. The results of source analysis showed that the five main sources of pollution were fossil fuel combustion and chemical production sources (33.73%, 9.71%, total source contribution rate of PMF and RF, respectively; the same below), natural sources and waste residue landfill (32.40%, 40.80%), traffic emissions (24.49%, 48.08%), coal burning and non-ferrous metal smelting (5.43%, 0.11%), and electroplating and ore smelting (3.95%, 1.30%). The simulation R 2 of the total variable of the two models were above 0.96, indicating that the models could predict heavy metals well. However, considering the actual situation of the number of enterprises in the park and roading density, the main pollution sources of soil heavy metals in the park should be industrial sources, and the simulation results of the PMF model were closer to the actual situation in the park.

Accumulating evidence has demonstrated that polysaccharides derived from edible fungi have lipid-lowering effects in mice. However, the lipid metabolism mechanisms in mice and humans are different. We have previously elucidated the structural characteristics of the alkali-extracted polysaccharide CM3-SII obtained from Cordyceps militaris. This study aimed to investigate whether CM3-SII could ameliorate hyperlipidemia in a heterozygous low-density lipoprotein receptor (LDLR)-deficient hamster model of hyperlipidemia. Our data demonstrated that CM3-SII significantly decreased total plasma cholesterol, non-high-density lipoprotein cholesterol, and triglyceride levels in heterozygous LDLR-deficient hamsters. Unlike ezetimibe, CM3-SII could enhance the concentration of plasma apolipoprotein A1 and the expression of liver X receptor α/ATP-binding cassette transporter G8 mRNA pathway and suppress the expression of Niemann-Pick C1-like 1, which help to reduce cholesterol levels further. Moreover, the results of molecular docking analysis demonstrated that CM3-SII could directly bind to Niemann-Pick C1-like 1 with high affinity. The triglyceride-lowering mechanisms of CM3-SII were related to its downregulation of sterol regulatory element-binding protein 1c and upregulation of peroxisome proliferator-activated receptor α. Importantly, CM3-SII increased the abundance of Actinobacteria and Faecalibaculum and the ratio of Bacteroidetes/Firmicutes. Thus, CM3-SII attenuated hyperlipidemia by modulating the expression of multiple molecules involved in lipid metabolism and the gut microbiota., Competing Interests: Declaration of competing interest The authors declare no competing financial interest., (Copyright © 2023. Published by Elsevier B.V.)

Objective: To explore the mechanism of early pancreatic exocrine function changes in severely scalded rats. Methods: The experimental research methods was used. Eighty male Sprague-Dawley rats aged 7-8 weeks were divided into simple sham injury group ( n =8), sham injury+cholecystokinin octapeptide (CCK8) group ( n =8), severe scald+CCK8 group ( n =32), and extremely severe scald+CCK8 group ( n =32) by the random number table, which were treated accordingly. Immediately after injury of rats in the 2 sham injury groups and 1, 2, 3, and 7 days after injury of rats in the 2 scald groups, the improved methods including pancreatic duct puncture and catheterization were used to dynamically collect the pancreatic-bile juice (PBJ) of rats. The PBJ secretory volume within 1 h was recorded, and the content of pancreatic lipase, α-amylase, and trypsin in PBJ was detected by enzyme-linked immunosorbent assay (ELISA), and the number of samples was 8. The femoral venous blood was collected, and the concentrations of pancreatic lipase and α-amylase in serum were detected by standard colorimetry to reflect their activity ( n =8). The pancreatic tissue was extracted, and the levels of interleukin-1β (IL-1β) and IL-6 in pancreatic tissue were detected by ELISA ( n =8), the expression of hypoxia-inducible factor 1α (HIF-1α) in pancreatic tissue was detected by immunofluorescence method, and the histopathological changes in pancreatic tissue were observed by hematoxylin-eosin staining, the severity of pancreatic tissue injury in the 2 scald groups was evaluated by modified Schmidt method ( n =6), and the ultrastructure of acinar cells in pancreatic tissue was observed by transmission electron microscopy. Data were statistically analyzed with analysis of variance for factorial design, Tukey test, independent sample t test, and least significant difference test. Results: Compared with the PBJ secretory volume (0.740±0.030) mL in the pancreatic tissue of rats in simple sham injury group within 1 h immediately after injury, the (0.823±0.033) mL in sham injury+CCK8 group was significantly increased ( t =4.92, P <0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the PBJ secretory volume of rats within 1 h in severe scald+CCK8 group ((0.681±0.024), (0.608±0.056), (0.525±0.025), and (0.720±0.044) mL) and extremely severe scald+CCK8 group ((0.540±0.025), (0.406±0.021), (0.475±0.036), and (0.690±0.018) mL) was significantly decreased on 1, 2, 3, and 7 days after injury ( P <0.05). Compared with that in severe scald+CCK8 group, the PBJ secretory volume of rats within 1 h in extremely severe scald+CCK8 group was significantly decreased on 1 and 2 days after injury ( P <0.05). Compared with that of rats in simple sham injury group immediately after injury, the content of pancreatic lipase, α-amylase, and trypsin in PBJ of rats in sham injury+CCK8 group immediately after injury was significantly increased (with t values of 4.56, 3.30, and 4.99, respectively, P <0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the content of pancreatic lipase and α-amylase in PBJ of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group was significantly decreased on 1, 2, 3, and 7 days after injury ( P <0.05), the trypsin content in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 2 days after injury ( P <0.05). Compared with that in severe scald+CCK8 group, the content of pancreatic lipase in PBJ of rats in extremely severe scald+CCK8 group was significantly decreased on 1, 2, and 3 days after injury ( P <0.05), and the content of α-amylase and trypsin in PBJ was significantly decreased on 1 and 2 days after injury ( P <0.05). There were no statistically significant differences in the activities of pancreatic lipase and α-amylase in serum of rats among the 4 groups at various time points after injury ( P >0.05). Compared with that of rats in sham injury+CCK8 group immediately after injury, the levels of IL-1β in pancreatic tissue of rats in severe scald+CCK8 group on 1, 2, and 3 days after injury and in extremely severe scald+CCK8 group on 1, 2, 3, and 7 days after injury were significantly increased ( P <0.05), and the levels of IL-6 in pancreatic tissue of rats in severe scald+CCK8 group and extremely severe scald+CCK8 group were significantly increased on 1, 2, 3, and 7 days after injury ( P <0.05). Compared with that in severe scald+CCK8 group, the IL-1β level in pancreatic tissue of rats in extremely severe scald+CCK8 group was significantly increased on 2 and 3 days after injury ( P <0.05), and IL-6 level in pancreatic tissue was significantly increased on 2 days after injury ( P <0.05). The expression levels of HIF-1α in pancreatic tissue of rats in simple sham injury group and sham injury+CCK8 group immediately after injury were lower; and compared with that in sham injury+CCK8 group immediately after injury, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups increased to a certain extent at different time points after injury, and the expression position was transited from the edge of the pancreatic tissue to the whole pancreas, the expression levels of HIF-1α in pancreatic tissue of rats in the 2 scald groups tended to be normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the proportion of acinar cell cytoplasm in pancreatic tissue of rats in sham injury+CCK8 group was increased; and with the increase of time after injury, edema, hemorrhage, necrosis, and inflammatory infiltration appeared in pancreatic tissue of rats in the 2 scald groups. Compared with that in severe scald+CCK8 group, the scores of edema, inflammatory cell infiltration, bleeding, and necrosis in pancreatic tissue of rats in extremely severe scald+CCK8 group were increased to varying degrees at various time points after injury, and the scores of pancreatic tissue of rats in the 2 scald groups basically recovered to normal on 7 days after injury. Compared with that in simple sham injury group immediately after injury, the number of enzyme granules in acinar cells of pancreatic tissue of rats in sham injury+CCK8 group was increased, and with the increase of time after injury, the enzyme granules in acinar cells of rats in the 2 scald groups were gradually reduced basically. Conclusions: The exocrine functions of pancreas, such as synthesis and secretion of pancreatic enzymes, are decreased in the early stage in severely scalded rats. And the greater the scalded area, the more significant the decline of pancreatic exocrine function. This change may be related to hypoxic injury and inflammation in pancreatic tissue after severe scald.

Objective: To evaluate the efficacy and safety of intravenous iron supplementation in patients with recurrent iron deficiency anemia (IDA) . Methods: This retrospective analysis of 90 patients with recurrent IDA from May 2012 to December 2021 was conducted, comparing the efficacy and safety of the intravenous iron therapy group and the oral iron therapy group. Results: Among the 90 patients with recurrent IDA, 20 were males and 70 were females, with a median age of 40 (range: 14-85) years. A total of 60 patients received intravenous iron supplementation and 30 received oral iron supplementation. The hematologic response rates in the intravenous iron group were significantly higher than those in the oral iron group at 4 and 8 weeks after treatment [80.0% (48/60) vs 3.3% (1/30) and 96.7% (58/60) vs 46.7% (14/30), all P <0.001, respectively]. The median increase in hemoglobin levels was also significantly higher in the intravenous iron group than in the oral iron group [38 (4, 66) g/L vs 7 (1, 22) g/L at week 4 and 44.5 (18, 80) g/L vs 19 (3, 53) g/L at week 8, all P <0.001]. The intravenous iron group had a significantly higher proportion of patients who achieved normal hemoglobin levels than the oral iron group (55.0% vs 0 and 90% vs 43.3%, all P<0.001, respectively). Iron metabolism indicators were tested before and after 8 weeks of treatment in 26 and 7 patients in the intravenous and oral iron groups, respectively. The median increase in serum ferritin (SF) levels in the intravenous iron group 8 weeks after treatment was 113.7 (49.7, 413.5) μg/L, and 54% (14/26) of these patients had SF levels of ≥100 μg/L, which was significantly higher than the median increase in SF levels in the oral iron group [14.0 (5.8, 84.2) μg/L, t =4.760, P <0.001] and the proportion of patients with SF levels of ≥100 μg/L ( P =0.013). The incidence of adverse reactions was 3.3% (2/60) in the intravenous iron group, which was significantly lower than that in the oral iron group [20.0% (6/30), P =0.015]. Conclusion: Intravenous iron supplementation is more effective for hematologic response, faster hemoglobin increase, and higher iron storage replenishment rates compared with oral iron supplementation in patients with recurrent IDA, and it is well tolerated by patients.

Backgrounds: It has been observed that high levels of enhancer of zeste homolog 2 (EZH2) expression are associated with unsatisfactory prognoses and can be found in a wide range of malignancies. However, the effects of EZH2 on Lung Adenocarcinoma (LUAD) remain elusive. Through the integration of bioinformatic analyses, the present paper sought to ascertain the effects of EZH2 in LUAD., Methods: The TIMER and UALCAN databases were applied to analyze mRNA and protein expression data for EZH2 in LUAD. The result of immunohistochemistry was obtained from the HPA database, and the survival curve was drawn according to the library provided by the HPA database. The LinkedOmics database was utilized to investigate the co-expressed genes and signal transduction pathways with EZH2. Up- and down-regulated genes from The Linked Omics database were introduced to the CMap database to predict potential drug targets for LUAD using the CMap database. The association between EZH2 and cancer-infiltrating immunocytes was studied through TIMER and TISIDB. In addition, this paper explores the relationship between EZH2 mRNA expression and NSCLC OS using the Kaplan-Meier plotter database to further validate and complement the research. Furthermore, the correlation between EZH2 expression and EGFR genes, KRAS genes, BRAF genes, and smoking from the Cancer Genome Atlas (TCGA) database is analyzed., Results: In contrast to paracancer specimens, the mRNA and protein levels of EZH2 were higher in LUAD tissues. Significantly, high levels of EZH2 were associated with unsatisfactory prognoses in LUAD patients. Additionally, the coexpressed genes of EZH2 were predominantly associated with numerous cell growth-associated pathways, including the cell cycle, DNA replication, RNA transport, and the p53 signaling pathway, according to Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathways. The results of TCGA database revealed that the expression of EZH2 was lower in normal tissues than in lung cancer tissues (p < 0.05). Smoking was associated with elevated EZH2 expression (p < 0.001). EZH2 was highly expressed in lung cancers with positive KRAS expression, and the correlation was significant in lung adenocarcinoma (r = 0.3129, p < 0.001). CMap was applied to determine the top 15 positively correlated drugs/molecules and the top 15 negatively correlated drugs/molecules. MK-1775, MK-5108, fenbendazole, albendazole, BAY-K8644, evodiamine, purvalanol-a, mycophenolic-acid, PHA-793887, and cyclopamine are potential drugs for patients with lung adenocarcinoma and high EZH2 expression., Conclusions: Highly expressed EZH2 is a predictor of a suboptimal prognosis in LUAD and may serve as a prognostic marker and target gene for LUAD. The underlying cause may be associated with the synergistic effect of KRAS, immune cell infiltration, and metabolic processes., (© 2023. The Author(s).)