Identification, in silico selection, and mechanistic investigation of antioxidant peptides from corn gluten meal hydrolysate.

Seven novel antioxidant peptides (AWF, LWQ, WIY, YLW, LAYW, LPWG, and LYFY) exhibiting a superior activity compared to trolox were identified through in silico screening. Among these, the four peptides (WIY, YLW, LAYW, and LYFY) displayed notably enhanced performance, with ABTS activity 2.58-3.26 times and ORAC activity 5.19-8.63 times higher than trolox. Quantum chemical calculations revealed that the phenolic hydroxyl group in tyrosine and the nitrogen-hydrogen bond in the indole ring of tryptophan serve as the critical sites for antioxidant activity. These findings likely account for the potent chemical antioxidant activity. The corn peptides also exerted a protective effect against AAPH-induced cytomorphologic changes in human erythrocytes by modulating the antioxidant system. Notably, LAYW exhibited the most pronounced cytoprotective effects, potentially due to its high content of hydrophobic amino acids.

Mesothelin CAR T Cells Secreting Anti-FAP/Anti-CD3 Molecules Efficiently Target Pancreatic Adenocarcinoma and its Stroma.

PURPOSE: Targeting solid tumors with chimeric antigen receptor (CAR) T cells remains challenging due to heterogenous target antigen expression, antigen escape, and the immunosuppressive tumor microenvironment (TME). Pancreatic cancer is characterized by a thick stroma generated by cancer-associated fibroblasts (CAF), which may contribute to the limited efficacy of mesothelin-directed CAR T cells in early-phase clinical trials. To provide a more favorable TME for CAR T cells to target pancreatic ductal adenocarcinoma (PDAC), we generated T cells with an antimesothelin CAR and a secreted T-cell-engaging molecule (TEAM) that targets CAF through fibroblast activation protein (FAP) and engages T cells through CD3 (termed mesoFAP CAR-TEAM cells). EXPERIMENTAL DESIGN: Using a suite of in vitro, in vivo, and ex vivo patient-derived models containing cancer cells and CAF, we examined the ability of mesoFAP CAR-TEAM cells to target PDAC cells and CAF within the TME. We developed and used patient-derived ex vivo models, including patient-derived organoids with patient-matched CAF and patient-derived organotypic tumor spheroids. RESULTS: We demonstrated specific and significant binding of the TEAM to its respective antigens (CD3 and FAP) when released from mesothelin-targeting CAR T cells, leading to T-cell activation and cytotoxicity of the target cell. MesoFAP CAR-TEAM cells were superior in eliminating PDAC and CAF compared with T cells engineered to target either antigen alone in our ex vivo patient-derived models and in mouse models of PDAC with primary or metastatic liver tumors. CONCLUSIONS: CAR-TEAM cells enable modification of tumor stroma, leading to increased elimination of PDAC tumors. This approach represents a promising treatment option for pancreatic cancer.

Targeting the activin receptor 1C on CD4+ T cells for cancer immunotherapy.

Activins, members of the TGF-beta superfamily, have been isolated and identified in the endocrine system, but have not been substantially investigated in the context of the immune system and endocrine-unrelated cancers. Here, we demonstrated that tumor-bearing mice had elevated systemic activin levels, which correlated directly with tumor burden. Likewise, cancer patients have elevated plasma activin levels compared to healthy controls. We observed that both tumor and immune cells could be sources of activins. Importantly, our in vitro studies suggest that activins promote differentiation of naïve CD4+ cells into Foxp3-expressing induced regulatory T cells (Tregs), particularly when TGF-beta was limited in the culture medium. Database and qRT-PCR analysis of sorted major immune cell subsets in mice revealed that activin receptor 1c (ActRIC) was uniquely expressed on Tregs and that both ActRIC and ActRIIB (activin receptor 2b) were highly upregulated during iTreg differentiation. ActRIC-deficient naïve CD4+ cells were found to be defective in iTreg generation both in vitro and in vivo. Treg suppression assays were also performed, and ActRIC deficiency did not change the function or stability of iTregs. Mice lacking ActRIC or mice treated with monoclonal anti-ActRIC antibody were more resistant to tumor progression than wild-type controls. This phenotype was correlated with reduced expression of Foxp3 in CD4+ cells in the tumor microenvironment. In light of the information presented above, blocking activin-ActRIC signaling is a promising and disease-specific strategy to impede the accumulation of immunosuppressive iTregs in cancer. Therefore, it is a potential candidate for cancer immunotherapy.

CXC chemokines: Potential biomarker and immunotherapeutic target for uterine corpus endometrial carcinoma.

Uterine corpus endometrial carcinoma (UCEC) is one of the most common type of gynecological malignancies. Multiple lines of evidence indicated that CXC chemokines exerted an anti-tumor immunological role in the tumor microenvironment which were critical regulators of cancer immunity. However, the relevance of CXC chemokines in the evaluation of prognosis and immune infiltration of UCEC remains to be explored. This study utilized various online databases, including TCGA, UALCAN, Kaplan-Meier Plotter, cBioPortal, TIMER2.0, TISIDB, and MethSurv to perform the analysis. Gene expression data from the TCGA-UCEC dataset indicated decreased expression of CXCL2/12 and increased expression of CXCL14/17. CXCL2/12 expression was negatively whereas CXCL14/17 expression was positively correlated with clinicopathological features of UCEC patients, including cancer stage, patients' age, weight and menopause status. Patients with higher CXCL12/14 expression corresponded with better clinical outcomes, which were not influenced by the genetic alterations. The differential expression of CXCL2/12/14/17 was not only significantly correlated with immune infiltration levels, but also the abundance of immune checkpoint inhibitors. Heatmaps of DNA methylation of CXCL2/12/14/17 were investigated, and 4 CpGs of CXCL2, 16 CpGs of CXCL12, 3 CpGs of CXCL14/17 were identified where altered methylation affected the prognosis of UCEC patients. These findings provided novel insights into the immunologic features of UCEC and might pave the way toward the prognostic evaluation and immunotherapy selection based on CXCL2/12/14/17 expression status.

The oncological safety and long-term cosmetic effect of free dermal fat graft with epidermis removal for breast defect repair in breast conserving surgery.

BACKGROUND: Free dermal fat grafts (FDFG) are used for immediate breast defect repair in breast-conserving surgery (BCS), and have achieved satisfactory immediate postoperative cosmetic effects (Sawai et al., 2004) [1]. However, the oncologic safety and long-term cosmetic outcomes of these surgical procedures remain unknown. Therefore, t，in this study, we aim to investigate the oncological safety and long-term cosmetic outcomes of FDFG in patients with breast cancer. METHODS: This matched retrospective case-control study included patients with non-special types of breast cancer who underwent FDFG for breast defect repair after BCS or BCS alone at two breast cancer research centers in Guangxi Province, China, from January 2016 to December 2019. The patients were divided into either the FDFG or BCS group. Control cases were screened using propensity score matching, and survival analysis and cosmetic evaluations were performed. RESULTS: A total of 442 patients with breast cancer were included in the study. After 1:4 propensity score matching, 53 and 212 patients were included in the FDFG and BCS groups, respectively. The median follow-up time was 49.9 (9.0-76.0) months. The rate of local recurrence in the FDFG group (9.4 %) was significantly higher than that in the BCS group (1.9 %; p < 0.05). The total cosmetic evaluation score was significantly higher in the BCS group 18 months after surgery than in the FDFG group (p < 0.05). CONCLUSIONS: In this retrospective study, FDFG was significantly associated with an increased risk of local recurrence. Further prospective studies are required to confirm these results. No significant difference in long-term cosmetic effects were observed for FDFG than for BCS alone for immediate breast defect repair.

Value of painless transvaginal four-dimensional hysterosalpingo contrast sonography in reducing venous intravasation: a comparative study.

OBJECTIVE: To investigate the value of painless transvaginal four-dimensional hysterosalpingo contrast sonography (TV 4-D HyCoSy) in reducing venous intravasation and its influencing factors through a retrospective comparative study on conventional TV 4-D HyCoSy. MATERIALS AND METHODS: A total of 451 patients were enrolled in this study from Jan. 2019 to Oct. 2021. There were 249 patients in the painless TV 4-D HyCoSy group and 202 patients in the conventional TV 4-D HyCoSy group. The incidence of venous intravasation and its related influencing factors were analyzed and compared between these two groups. The difficulty of image evaluation for the diagnosis was also compared. RESULTS: There was no significant difference in the baseline characteristics between the painless group and the conventional group (p > 0.05). Compared with the conventional group, the painless group had a lower incidence of venous intravasation (16.9 vs. 24.8%; p = 0.039). Painless TV 4-D HyCoSy was more effective in reducing venous intravasation in patients with primary infertility (p = 0.032) without a history of pelvic surgery (p = 0.008) or ectopic pregnancy (p = 0.018). Logistic regression analysis demonstrated that painless TV 4-D HyCoSy and endometrial thickness > 5 mm were protective factors for venous intravasation. Moreover, the diagnostic procedure was easier in the painless group than in the conventional group (p = 0.002). CONCLUSIONS: Painless TV 4D-HyCoSy may be an effective mode in reducing the incidence of venous intravasation and improving the diagnosis of patency of fallopian tubes.

Risk Factors of Acute Pain in Elderly Patients After Laparoscopic Radical Resection of Colorectal Cancer.

OBJECTIVE: To investigate the risk factors of acute pain after laparoscopic radical resection of colorectal cancer (CRC) in elderly patients. METHODS: Totally, 143 elderly patients (≥ 60 y old) who received laparoscopic radical resection of CRC in the People's Hospital of Xinjiang Uygur Autonomous Region from March 2021 to August 2022 were retrospectively analyzed. The patients were divided into 2 groups according to visual analog scale (VAS) scores 24 h after surgery: mild pain group (VAS score ≤ 3, n=108) and moderate to severe pain group (VAS score >3, n=35). The data of the patients, including sex, age, height, body mass, intraoperative blood loss, intraoperative urine volume, intraoperative opioid dosage, operation duration, preoperative Hospital Anxiety and Depression Scale (HADS) scores, preoperative Mini-Mental State Examination scores, VAS scores, postoperative nausea and vomiting scores were recorded. Multivariate logistic regression analysis was used to screen the risk factors of postoperative acute pain in elderly patients undergoing laparoscopic radical resection of CRC. RESULTS: The preoperative HADS score of the moderate to severe pain group was significantly increased compared with that of the mild pain group (10.8±2.4 vs. 6.2±1.9), as well as the operation duration (226.4±18.3 vs. 186.1±12.7), the intraoperative dosage of remifentanil (3.7±0.2 vs. 3.2±0.4), the preoperative VAS score [4(2, 7) vs. 2 (0, 4)] and postoperative VAS score [5 (4, 6) vs. 3 (2, 3)] ( P <0.05). Multivariate logistic regression analysis showed that high preoperative HADS score, long operation duration, and high preoperative VAS score ( P <0.05) were independent risk factors for acute pain after laparoscopic radical resection of CRC in elderly patients. CONCLUSION: Preoperative anxiety and depression, preoperative pain, and long operation duration are risk factors for acute pain in elderly patients after laparoscopic radical resection of CRC.

Anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma.

BACKGROUND AND PURPOSE: To identify anatomic prognostic factors and their potential roles in refining M1 classification for de novo metastatic nasopharyngeal carcinoma (M1-NPC). MATERIALS AND METHODS: All M1-NPC treated with chemotherapy and/or radiotherapy between 2010 and 2019 from two centers (training and validation cohort) were included. The prognostic value of metastatic disease extent and involved organs for overall survival (OS) were assessed by several multivariable analyses (MVA) models. A new M1 classification was proposed and validated in a separate cohort who received immuno-chemotherapy. RESULTS: A total of 197 M1-NPC in the training and 307 in the validation cohorts were included for M1 subdivision study with median follow-up of 46 and 57 months. MVA model with "≤2 organs/≤5 lesions" as the definition of oligometastasis had the highest C-index (0.623) versus others (0.606-0.621). Patients with oligometastasis had better OS versus polymetastasis (hazard ratio [HR] 0.47/0.63) while liver metastases carried worse OS (HR 1.57/1.45) in MVA in the training/validation cohorts, respectively. We proposed to divide M1-NPC into M1a (oligometastasis without liver metastases) and M1b (liver metastases or polymetastasis) with 3-year OS of 66.5%/31.7% and 64.9%/35.0% in the training/validation cohorts, respectively. M1a subset had a better median progress-free survival (not reach vs. 17 months, p < 0.001) in the immuno-chemotherapy cohort (n = 163). CONCLUSION: Oligometastasis (≤2 organs/≤5 lesions) and liver metastasis are prognostic for M1-NPC. Subdivision of M1-NPC into M1a (oligometastasis without liver metastasis) and M1b (liver metastasis or polymetastasis) depicts the prognosis well in M1-NPC patients who received immuno-chemotherapy.

Risk stratification of gastric cancer screening in community population based on oral contrast-enhanced ultrasonography examination: A 3-year follow-up analysis report.

Objective: This study aimed to retrospectively investigate the use of oral contrast-enhanced ultrasonography (O-CEUS) in assessing the thickness of the gastric wall for gastric cancer (GC) screening and to establish screening strategies for GC with different risk stratifications based on the gastric wall thickness. Methods: From January 2015 to March 2020, people who underwent O-CEUS at the Physical Examination Center of our hospital with at least three years of follow-up were included in this study. The thickness of the gastric wall measured by O-CEUS was divided into three groups using 6 mm and 9 mm as cutoff values. The occurrence of GC in each group was observed. The imaging and clinical information of these populations were recorded and analyzed. Kaplan-Meier survival analysis and Cox's proportional hazards regression were performed to calculate the risk of GC occurrence. Results: A total of 4,047 people were finally included in this study. During the follow-up period, GC occurred in 7 individuals (incidence rate 0.17%). Among them, according to the thickness of the gastric wall, one case occurred in Group A (< 6 mm), two cases occurred in Group B (6-9 mm), and four cases occurred in Group C (>9mm). Based on Kaplan-Meier survival analysis, the curves of the three groups were significantly different (P < 0.01). The risk of GC occurrence in Group C and Group B were higher than that in Group A (4.76E+2-fold and 1.50E+2-fold). Conclusion: O-CEUS is a convenient, economical, safe, and noninvasive screening method for GC. Measuring the thickness of the gastric wall is helpful to predict the risk of GC occurrence according to our stratification screening system.

Tumor- and Nerve-Derived Axon Guidance Molecule Promotes Pancreatic Ductal Adenocarcinoma Progression and Metastasis through Macrophage Reprogramming.

Axon guidance molecules were found to be the gene family most frequently altered in pancreatic ductal adenocarcinoma (PDA) through mutations and copy number changes. However, the exact molecular mechanism regarding PDA development remained unclear. Using genetically engineered mouse models to examine one of the axon guidance molecules, semaphorin 3D (SEMA3D), we found a dual role for tumor-derived SEMA3D in malignant transformation of pancreatic epithelial cells and a role for nerve-derived SEMA3D in PDA development. This was demonstrated by the pancreatic-specific knockout of the SEMA3D gene from the KRAS G12D and TP53 R 172 H mutation knock-in, PDX1-Cre (KPC) mouse model which demonstrated a delayed tumor initiation and growth comparing to the original KPC mouse model. Our results showed that SEMA3D knockout skews the macrophages in the pancreas away from M2 polarization, providing a potential mechanistic role of tumor-derived SEMA3D in PDA development. The KPC mice with the SEMA3D knockout remained metastasis-free, however, died from primary tumor growth. We then tested the hypothesis that a potential compensation mechanism could result from SEMA3D which is naturally expressed by the intratumoral nerves. Our study further revealed that nerve-derived SEMA3D does not reprogram macrophages directly, but reprograms macrophages indirectly through ARF6 signaling and lactate production in PDA tumor cells. SEMA3D increases tumor-secreted lactate which is sensed by GPCR132 on macrophages and subsequently stimulates pro-tumorigenic M2 polarization in vivo. Tumor intrinsic- and extrinsic-SEMA3D induced ARF6 signaling through its receptor Plexin D1 in a mutant KRAS-dependent manner. Consistently, RNA sequencing database analysis revealed an association of higher KRAS MUT expression with an increase in SEMA3D and ARF6 expression in human PDAs. Moreover, multiplex immunohistochemistry analysis showed an increased number of M2-polarized macrophages proximal to nerves in human PDA tissue expressing SEMA3D. Thus, this study suggests altered expression of SEMA3D in tumor cells lead to acquisition of cancer-promoting functions and the axon guidance signaling originating from nerves is "hijacked" by tumor cells to support their growth. Other axon guidance and neuronal development molecules may play a similar dual role which is worth further investigation. One sentence summary: Tumor- and nerve-derived SEMA3D promotes tumor progression and metastasis through macrophage reprogramming in the tumor microenvironment. STATEMENT OF SIGNIFICANCE: This study established the dual role of axon guidance molecule, SEMA3D, in the malignant transformation of pancreatic epithelial cells and of nerve-derived SEMA3D in PDA progression and metastasis. It revealed macrophage reprogramming as the mechanism underlying bothroles. Together, this research elucidated how inflammatory responses promote invasive PDA progression and metastasis through an oncogenic process.

Combination therapy of HIFα inhibitors and Treg depletion strengthen the anti-tumor immunity in mice.

Hypoxia-inducible factor 1 alpha (HIF1α), under hypoxic conditions, is known to play an oxygen sensor stabilizing role by exerting context- and cell-dependent stimulatory and inhibitory functions in immune cells. Nevertheless, how HIF1α regulates T cell differentiation and functions in tumor settings has not been elucidated. Herein, we demonstrated that T-cell-specific deletion of HIF1α improves the inflammatory potential and memory phenotype of CD8+ T cells. We validated that T cell-specific HIF1α ablation reduced the B16 melanomas development with the indication of ameliorated antitumor immune response with enhanced IFN-γ+ CD8+ T cells despite the increase in the Foxp3+ regulatory T-cell population. This was further verified by treating tumor-bearing mice with a HIF1α inhibitor. Results indicated that HIF1α inhibitor also recapitulates HIF1α ablation effects by declining tumor growth and enhancing the memory and inflammatory potential of CD8+ T cells. Furthermore, a combination of Treg inhibitor with HIF1α inhibitor can substantially reduce tumor size. Collectively, these findings highlight the notable roles of HIF1α in distinct CD8+ T-cell subsets. This study suggests the significant implications for enhancing the potential of T cell-based antitumor immunity by combining HIF1α and Tregs inhibitors.

Metagenomic next-generation sequencing in the diagnosis of neurocysticercosis: A case report.

BACKGROUND: The clinical symptoms and imaging manifestations of neurocysticercosis (NCC) are very different, and the difficulty and delay of clinical diagnoses may lead to an increase in mortality and disability. Rapid and accurate pathogen identification is important for the treatment of these patients. Metagenomic next-generation sequencing (mNGS) is a powerful tool to identify pathogens, especially in infections that are difficult to identify by conventional methods. CASE SUMMARY: A 43-year-old male patient was admitted due to a recurrent headache for a few months. Imaging examinations showed hydrocephalus and cystic lesions, which were considered to be a central nervous system infection, but no etiology was found by routine examination. mNGS of the cerebrospinal fluid revealed high Taenia solium reads, and the positive results of a cysticercosis antibody test confirmed the infection. Combined with the patient's clinical manifestations, the etiological evidence, and the imaging manifestation, the patient was finally diagnosed with NCC and he was prescribed dexamethasone, albendazole, neurotrophic drugs, and intracranial pressure reduction therapy. The headaches disappeared after anti-parasite treatment, and no associated symptoms recurred prior to the three- and six-month follow-up. CONCLUSION: As an accurate and sensitivity detection method, mNGS can be a reliable approach for the diagnosis of NCC.

Engineered TCR T-cell therapy targeting mass spectrometry-identified natural epitope in PDAC.

Tumor antigens are crucial targets for T-cell-based therapy to induce tumor-specific rejection. However, identifying pancreatic ductal adenocarcinoma (PDAC)-specific T-cell epitopes has been challenging. Using advanced mass spectrometry (MS) analysis, we previously identified cancer-associated, class I MHC-bound epitopes shared by multiple PDAC patients with different HLA-A types. Here, we investigated one of these epitopes, LAMC2203-211, a naturally occurring nonmutated epitope on the LAMC2 protein. Following stimulation with the LAMC2203-211 peptide, we cloned T-cell receptors (TCRs) and transduced them into the Jurkat human T-cell line using a lentiviral vector. We found that Jurkat cells expressing LAMC2203-211-specific TCRs resulted in potent, LAMC2 specific, in vitro cytotoxic effects on PDAC cells. Furthermore, in mice that harbored either subcutaneously or orthotopically implanted tumors originating from both HLA-A allele-matched and unmatched PDAC patients, tumor growth was suppressed in a LAMC2-dependent manner following the infusion of LAMC2-targeting T cells. We have therefore developed a LAMC2-specific TCR-based T-cell therapy strategy likely suitable for many PDAC patients. This is the first study to adopt MS analysis to identify natural CD8+ T-cell epitopes in PDAC that could potentially serve as targets for PDAC immunotherapy.

CLDN18.2 BiTE Engages Effector and Regulatory T Cells for Antitumor Immune Response in Preclinical Models of Pancreatic Cancer.

BACKGROUND & AIMS: BiTE (bispecific T-cell engager) immune therapy has demonstrated clinical activity in multiple tumor indications, but its influence in the tumor microenvironment remains unclear. CLDN18.2 is overexpressed in solid tumors including gastric cancer (GC) and pancreatic ductal adenocarcinoma (PDAC), both of which are characterized by the presence of immunosuppressive cells, including regulatory T cells (Tregs) and few effector T cells (Teffs). METHODS: We evaluated the activity of AMG 910, a CLDN18.2-targeted half-life extended (HLE) BiTE molecule, in GC and PDAC preclinical models and cocultured Tregs and Teffs in the presence of CLDN18.2-HLE-BiTE. RESULTS: AMG 910 induced potent, specific cytotoxicity in GC and PDAC cell lines. In GSU and SNU-620 GC xenograft models, AMG 910 engaged human CD3+ T cells with tumor cells, resulting in significant antitumor activity. AMG 910 monotherapy, in combination with a programmed death-1 (PD-1) inhibitor, suppressed tumor growth and enhanced survival in an orthotopic Panc4.14 PDAC model. Moreover, Treg infusion enhanced the antitumor efficacy of AMG 910 in the Panc4.14 model. In syngeneic KPC models of PDAC, treatment with a mouse surrogate CLDN18.2-HLE-BiTE (muCLDN18.2-HLE-BiTE) or the combination with an anti-PD-1 antibody significantly inhibited tumor growth. Tregs isolated from mice bearing KPC tumors that were treated with muCLDN18.2-HLE-BiTE showed decreased T cell suppressive activity and enhanced Teff cytotoxic activity, associated with increased production of type I cytokines and expression of Teff gene signatures. CONCLUSIONS: Our data suggest that BiTE molecule treatment converts Treg function from immunosuppressive to immune enhancing, leading to antitumor activity in immunologically "cold" tumors.

The effect of the multiple arterial grafts compared with single arterial graft for coronary artery bypass grafting on sternal wound complications: A meta-analysis.

A meta-analysis investigation was executed to measure the influence of multiple arterial grafts (MAGs) compared with single arterial graft (SAG) for coronary artery bypass grafting (CABG) on sternal wound complications (SWCs). A comprehensive literature inspection till February 2023 was applied and 1048 interrelated investigations were reviewed. The seven chosen investigations enclosed 11 201 individuals with CABG in the chosen investigations' starting point, 4870 of them were using MAGs, and 6331 were using SAG. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilised to compute the value of the effect of the MAGs compared with SAG for CABG on SWCs by the dichotomous approaches and a fixed or random model. MAGs had significantly higher SWC (OR, 1.38; 95% CI, 1.10-1.73, P = .005) compared with those with SAG in CABG. MAGs had significantly higher SWC compared with those with SAG in CABG. However, care must be exercised when dealing with its values because of the low number of selected investigations for the meta-analysis.

Enhancing the effect of biochar ageing on reducing cadmium accumulation in Medicago sativa L.

Biochar (BC) application to farmland soil can reduce the mobility and bioavailability of Cd. Nevertheless, BC is prone to natural ageing in soil, which alters its structure, physicochemical properties, thereby affecting the immobilisation of Cd. We used dry-wet and freeze-thaw cycles to mimic the natural ageing of BC, and used adsorption experiments to explore the changes of Cd adsorption capacity of BC and aged BC (ABC). We conducted a pot experiment to investigate the effects of BC and ABC on soil biotic and abiotic factors, alfalfa growth, and Cd accumulation in agricultural soils with high and low Cd concentrations. The increase of specific surface area, pore size, oxygen containing functional groups and mineral composition leads to better adsorption capacity of ABC. The adsorption of Cd(II) by BC and ABC is mainly by monolayer adsorption and chemical adsorption. Applying BC and ABC to Cd-contaminated soil significantly increased the aboveground biomass and decreased the Cd accumulation by reducing the Cd bioconcentration factor in alfalfa. At high Cd levels, adding BC and ABC reduced the Cd content in alfalfa shoots by 32.8 % and 35.1 %, respectively; the fixing effect of ABC was better than that of BC. Adding BC and ABC significantly increased the microbial biomass and geometric mean of enzymes. BC addition increased soil pH by 0.32-0.36 units and cation exchange capacity (CEC) by 15.5 %. Adding BC and ABC significantly increased soil organic matter (SOM) by 5.7 % and 6.2 %, respectively. Random forest analysis showed that SOM, total organic carbon, and fluorescein diacetate hydrolase were important variables for Cd content in alfalfa shoots. Structural equation modelling showed that BC indirectly affected the Cd content in alfalfa shoots by affecting soil pH, CEC, SOM, microbial biomass, and microbial metabolic activity. BC has a long-term effect on alleviating Cd pollution in farmland.

Genetic alterations in the neuronal development genes are associated with changes of the tumor immune microenvironment in pancreatic cancer.

Background: Pancreatic ductal adenocarcinoma (PDAC) has a poor prognosis and is highly metastatic. Our prior studies have demonstrated the critical role of axon guidance pathway genes in PDAC and the connection between neuronal development and the tumor microenvironment. A recent study newly identified 20 neuronal development genes [disks large homolog 2 (DLG2), neuron-glial-related cell adhesion molecule (NRCAM), neurexin3 (NRXN3), mitogen-activated protein kinase 10 (MAPK10), platelet-derived growth factor D (PDGFD), protein kinase C epsilon (PRKCE), potassium calcium-activated channel subfamily M alpha 1 (KCNMA1), polycystic kidney and hepatic disease 1 (PKHD1), neural cell adhesion molecule 1 (NCAM1), neuregulin-1 (NRG1), zinc finger protein 667 (ZNF667), cystic fibrosis transmembrane conductance regulator (CFTR), acyl-CoA medium-chain synthetase-3 (ACSM3), complement 6 (C6), protein tyrosine phosphatase receptor type M (PTPRM), hypoxia-inducible factor 1 alpha (HIF1A), adenylyl cyclase 5 (ADCY5), adherens junctions-associated protein 1 (AJAP1), neurobeachin (NBEA), sodium voltage-gated channel alpha subunit 9 (SCN9A)] that are associated with perineural invasion and poor prognosis of PDAC. The relationship between genetic alterations in these 20 genes and tumor immune microenvironment (TME) has not previously been investigated. Methods: We hence applied the sequential multiplex immunohistochemistry results of biopsy specimens from 63 PDAC patients to investigate this relationship. Results: We found that, except for PTPRM and NBEA, genetic alterations involving these 20 genes are associated with significant changes in the densities of major immune cell subtypes. Except for AJAP1, the copy number loss involving this panel of neuronal development genes is significantly associated with changes in immune cell infiltrates. In contrast, the copy number gain in fewer genes, including NRXN3, ZNF667, ACSM3, C6, ADCY5, SCN9A, and PRKCE, is significantly associated with changes in immune cell infiltrates. Conclusions: Our study suggested that neuronal development genes play a role in modulating TME in a pancreatic cancer setting.

Microstructure and Texture Characterization of Duplex Stainless Steel Joints Welded by Alternating Magnetic Field-Assisted Hybrid Laser-GMAW Welding.

In this study, 2205 duplex stainless steel with 12 mm thickness was welded by alternating magnetic field-assisted laser arc hybrid welding. The effect of an alternating magnetic field on the proportion distribution of two phases of the welded joint was investigated. The texture distribution, grain boundary misorientation, and grain size of welded joints were analyzed and characterized. The uniform distribution of alloying elements in the two phases was improved by a 20 mT alternating magnetic field. The diffusion dissolution of Ni and N elements into the γ phase was promoted, which was conducive to the transition from the α to γ phase and reduced the precipitation of Cr2N, such that the ratio of γ to α was 43.4:56.6. The ratio of the two phases of the weld was balanced by the alternating magnetic field of 30 mT, such that the ratio of γ and α was 44.6:55.4 and the texture dispersion was weakened. The Σ3 twinning boundary of the austenite phase in the weld was transformed to HABs, the ferrite phase underwent dynamic recrystallization, and the austenite phase had a cube texture, copper texture, and goss texture.

ALG2 inhibits the epithelial-to-mesenchymal transition and stemness of ovarian granulosa cells through the Wnt/ß-catenin signaling pathway in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects fertility in women of reproductive age, and a leading cause of anovulatory infertility. Ovarian granulosa cells are a major functional cell type in the ovary that undergo epithelial-to-mesenchymal transition (EMT) to initiate ovulation. Protein glycosylation, catalyzed by specific glycosyltransferases, has been implicated in reproductive events, such as embryo implantation, endometrial receptivity, and decidualization, etc. However, the relationship between glycosylation and EMT-mediated ovulation in PCOS is not well understood. To clarify the role of cobalt chloride (CoCl2) and α-1,3/1,6-mannosyltransferase (ALG2) in PCOS, transwell assay, Real-time PCR, Western blot, immunofluorescence, and sphere formation assay were applied to assess cell migration, invasion, EMT, and stemness of ovarian granulosa cells. Enzyme-linked immunosorbent assay (ELISA) was performed to measure the serum level of ALG2 in PCOS patients. We found that CoCl2 promoted the migration, invasion, EMT, and stemness of ovarian granulosa cells by downregulating the expression of ALG2. Upregulation of ALG2 rescued the effects of CoCl2 partially, and inhibited the EMT and stemness of ovarian granulosa cells by inactivating the Wnt/ß-catenin signaling pathway. Moreover, the serum level of ALG2 was increased in patients with PCOS. Elevated ALG2, in combination with testosterone, represented better diagnostic value for PCOS as a multimarker than ALG2 or testosterone alone as a single marker. Thus, ALG2, downregulated by CoCl2, was increased in PCOS patients which inhibited the EMT and stemness of ovarian granulosa cells by deactivating the Wnt/ß-catenin signaling pathway. The combination of ALG2 and testosterone might thus act as a novel but promising biomarker for PCOS detection.

Effect of intradermal needle therapy at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors.

BACKGROUND: Postoperative gastrointestinal function recovery is critical for rapid rehabilitation of patients with gastrointestinal tumors. Traditional Chinese medicine offers considerable advantages for gastrointestinal disease treatment. However, no study has reported the clinical efficacy of intradermal needle therapy (INT) at the Yuan-source, Luo-connecting, and He-sea points of the corresponding meridian for gastrointestinal function in patients following surgery for gastrointestinal tumors. AIM: To investigate the effect of INT at combined acupoints on patients' gastrointestinal function following surgery for gastrointestinal tumors. METHODS: This randomized controlled trial was conducted at the Second Affiliated Hospital of Xi'an Jiaotong University on patients with diagnosed gastrointestinal cancer, no distant metastases or organ failure, and hospitalized for elective radical tumor resection, who did not receive preoperative radiotherapy or chemotherapy. Participants were randomly allocated to either the intervention (n = 32) or the control (n = 32) group. Participants in the control group received enhanced recovery care, while those in the intervention group received enhanced recovery care combined with INT at the Yuan-source, Luo-connecting, and He-sea points. After surgery, INT was performed immediately upon the patient's return to the ward, and continued for seven consecutive days. The independent samples t-test, chi-square test, and generalized estimating equations were used for data analysis. RESULTS: The participants' ages ranged from 40 to 80 years (average 63 ± 10.1 years). Most participants underwent surgery for either gastric (43.8%) or colon cancer (39.1%) and had adenocarcinoma (87.5%). Significant differences were noted in time to first postoperative flatus passage (66 ± 27 h vs 103 ± 41 h, P < 0.001), time to first defecation (106 ± 44 h vs 153 ± 50 h, P < 0.001), and time to first oral feeding (73 ± 30 h vs 115 ± 38 h, P < 0.001) between the intervention and control groups. Gastrointestinal symptoms, including abdominal distension, nausea, and fatigue 48 h and 72 h after surgery, were significantly alleviated in the intervention group compared with that observed in the control group (P < 0.05). CONCLUSION: INT at the Yuan-source, Luo-connecting, and He-sea points can promote recovery of gastrointestinal function and ease gastrointestinal symptoms in patients following surgical resection of gastrointestinal tumors.