LILRB4 on multiple myeloma cells promotes bone lesion by p-SHP2/NF-κB/RELT signal pathway.

BACKGROUND: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. METHODS: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. RESULTS: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. CONCLUSIONS: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Elucidating the photodegradation mechanism of octylisothiazolinone and dichlorooctylisothiazolinone in surface water: An in-depth comprehensive analysis.

Octylisothiazolinone (OIT) and Dichlorooctylisothiazolinone (DCOIT), widely used antibacterial agents in coatings, have seen a sharp increase in use in response to the Coronavirus disease 2019 (Covid-19) pandemic, ultimately leading to their increase in the aquatic environment. However, their photodegradation process in surface water is still unclear. The purpose of this study is to investigate the photodegradation kinetics and mechanisms of OIT and DCOIT in natural water environments. Under simulated solar irradiation, they undergo direct photolysis in both natural freshwater and seawater mainly via their excited singlet states, while no self-sensitization photolysis was observed. The direct photolysis rate constants of OIT and DCOIT were 1.19 ± 0.07 and 0.57 ± 0.03 h-1, respectively. In addition, dissolved organic matter (DOM), NO3- and Cl- in natural waters did not contribute significantly to the photodegradation, and the light screening effect of DOM was identified as the main inhibiting factor. The photodegradation half-life of OIT was estimated to be 0.66 to 1.69 days, while the half-life of DCOIT was as high as 20.9 days during winter in surface water at 30°N latitude. Ring opening of the N-S bond and covalent bond breaking between CN are the main pathways for the photodegradation of OIT and DCOIT, which is verified by density-functional theory calculations. Ecological Structure Activity Relationships (ECOSAR) results indicate that OIT and DCOIT have "Very Toxic" biological toxicity, and the acute toxicity of their products is significantly reduced. It is noteworthy that the toxicity of the products of DCOIT is generally higher than that of OIT, and the chronic toxicity of most of the products is still above the "Toxic" level. Therefore, an in-depth understanding of the photodegradation mechanisms of OIT and DCOIT in aqueous environments is crucial for accurately assessing their ecological risks in natural water environments.

Pecan (Carya illinoinensis (Wangenh.) K. Koch) nuts as an emerging source of protein: extraction, physicochemical and functional properties.

BACKGROUND: The increasing demand for sustainable alternatives to traditional protein sources, driven by population growth, underscores the importance of protein in a healthy diet. Pecan (Carya illinoinensis (Wangenh.) K. Koch) nuts are currently underutilized as plant-based proteins but hold great potential in the food industry. However, there is insufficient information available on pecan protein, particularly its protein fractions. This study aimed to explore the physicochemical and functional properties of protein isolate and the main protein fraction glutelin extracted from pecan nuts. RESULTS: The results revealed that glutelin (820.67 ± 69.42 g kg-1) had a higher crude protein content compared to the protein isolate (618.43 ± 27.35 g kg-1), while both proteins exhibited amino acid profiles sufficient for adult requirements. The isoelectric points of protein isolate and glutelin were determined to be pH 4.0 and pH 5.0, respectively. The denaturation temperature of the protein isolate (90.23 °C) was higher than that of glutelin (87.43 °C), indicating a more organized and stable conformation. This is further supported by the fact that the protein isolate had a more stable main secondary structure than glutelin. Both proteins demonstrated improved solubility, emulsifying, and foaming properties at pH levels deviating from their isoelectric points in U-shaped curves. Compared to the protein isolate, glutelin displayed superior water and oil absorption capacity along with enhanced gelling ability. CONCLUSION: The protein isolate and glutelin from pecan nuts exhibited improved stability and competitive functional properties, respectively. The appropriate utilization of these two proteins will support their potential as natural ingredients in various food systems. © 2024 Society of Chemical Industry.

[Comparsion of bone setting technique combined with percutaneous vertebroplasty and percutaneous kyphoplasty for the treatment of osteoporotic vertebral compression fractures].

OBJECTIVE: To explore clinical efficacy of osteoplasty combined with percutaneous vertebroplasty(PVP) and percutaneous kyphoplasty (PKP) alone in treating osteoporosis vertebral compression fractures (OVCFs). METHODS: The clinical data of 80 patients with single-level OVCFs treated from January 2021 to June 2022 were retrospectively analyzed, and were divided into treatment group and control group according to different surgical methods, 40 patients in each group. In treatment group, there were 24 males and 16 females, aged from 60 to 83 years old with an average of (70.43±7.31) years old;bone mineral density ranged from -3.30 to -2.50 SD with an average of(-2.84±0.24) SD;1 patient with T10, 4 patients with T11, 11 patients with T12, 7 patients with L1, 7 patients with L2, 5 patients with L3, 3 patients with L4, 2 patients with L5;bone setting technique combined with PVP were performed. In control group, there were 27 males and 13 females, aged from 60 to 82 years old with an average of (68.98±6.94) years old;bone mineral density ranged from -3.40 to -2.50 SD with an average of (-2.76±0.23) SD;2 patients with T10, 3 patients with T11, 13 patients with T12, 11 patients with L1, 5 patients with L2, 3 patients with L3, 2 patients with L4, 1 patient with L5;simple PKP were peformed. Visual analogue scale (VAS) and lumbar Oswestry disability index (ODI) were compared between two groups before operation, 3 days, 3 and 12 months after operation. The changes of local kyphotic angle, vertebral wedge angle and vertebral anterior margin height ratio were compared between two groups before operation, 3 days and 12 months after operation. RESULTS: All patients were successfully completed operation. Treatment group were followed up from 13 to 22 months with an average of (16.82±2.14) months, and control group were followed up from 13 to 23 months with an average of (16.45±2.56) months. Three patients were occurred bone cement leakage in treatment group, while 1 patient were occurred bone cement leakage and 1 patient occurred sensory disturbance of lower limb skin in control group;there were no significant difference in complications between two groups (P>0.05). There were no significant difference in preoperative VAS and ODI between two groups (P>0.05). At 3 days after operation, VAS of treatment group 3.68±0.62 was significantly higher than that of control group 4.00±0.72 (P<0.05). There were no significant difference in VAS and ODI between two groups at 3 and 12 months after operation (P>0.05). There were no significant difference in local kyphotic angle, vertebral wedge angle and vertebral anterior margin height between two groups at 3 days and 12 months after operation (P>0.05). CONCLUSION: Compared with PKP, bone setting manipulation combined with PVP for the treatment of OVCFs has advantages in early postoperative pain relief. In terms of vertebral height recovery, bone setting manipulation combined with PVP and PKP alone have similar clinical effects.

Celastrol Regulates the Hsp90-NLRP3 Interaction to Alleviate Rheumatoid Arthritis.

Previous studies have verified that celastrol (Cel) protects against rheumatoid arthritis (RA) by inhibiting the NLRP3 inflammasome signaling pathway, but the molecular mechanism by which Cel regulates NLRP3 has not been clarified. This study explored the specific mechanisms of Cel in vitro and in vivo. A type II collagen-induced arthritis (CIA) mouse model was used to study the antiarthritic activity of Cel; analysis of paw swelling, determination of the arthritis score, and pathological examinations were performed. The antiproliferative and antimigratory effects of Cel on TNF-α induced fibroblast-like synoviocytes (FLSs) were tested. Proinflammatory factors were evaluated using enzyme-linked immunosorbent assay (ELISA). The expression of NF-κB/NLRP3 pathway components was determined by western blotting and immunofluorescence staining in vitro and in vivo. The putative binding sites between Cel and Hsp90 were predicted through molecular docking, and the binding interactions were determined using the Octet RED96 system and coimmunoprecipitation. Cel decreased arthritis severity and reduced TNF-α-induced FLSs migration and proliferation. Additionally, Cel inhibited NF-κB/NLRP3 signaling pathway activation, reactive oxygen species (ROS) production, and proinflammatory cytokine secretion. Furthermore, Cel interacted directly with Hsp90 and blocked the interaction between Hsp90 and NLRP3 in FLSs. Our findings revealed that Cel regulates NLRP3 inflammasome signaling pathways both in vivo and in vitro. These effects are induced through FLSs inhibition of the proliferation and migration by blocking the interaction between Hsp90 and NLRP3.

Multi-dimensional cell-free DNA-based liquid biopsy for sensitive early detection of gastric cancer.

BACKGROUND: Gastric cancer is the fifth most common cancer type. Most patients are diagnosed at advanced stages with poor prognosis. A non-invasive assay for the detection of early-stage gastric cancer is highly desirable for reducing associated mortality. METHODS: We collected a prospective study cohort of 110 stage I-II gastric cancer patients and 139 non-cancer individuals. We performed whole-genome sequencing with plasma samples and profiled four types of cell-free DNA (cfDNA) characteristics, fragment size pattern, copy number variation, nucleosome coverage pattern, and single nucleotide substitution. With these differential profiles, we developed an ensemble model to detect gastric cancer signals. Further, we validated the assay in an in-house first validation cohort of 73 gastric cancer patients and 94 non-cancer individuals and an independent second validation cohort of 47 gastric cancer patients and 49 non-cancer individuals. Additionally, we evaluated the assay in a hypothetical 100,000 screening population by Monte Carlo simulation. RESULTS: Our cfDNA-based assay could distinguish early-stage gastric cancer from non-cancer at an AUROC of 0.962 (95% CI: 0.942-0.982) in the study cohort, 0.972 (95% CI: 0.953-0.992) in the first validation cohort and 0.937 (95% CI: 0.890-0.983) in the second validation cohort. The model reached a specificity of 92.1% (128/139) and a sensitivity of 88.2% (97/110) in the study cohort. In the first validation cohort, 91.5% (86/94) of non-cancer individuals and 91.8% (67/73) of gastric cancer patients were correctly identified. In the second validation cohort, 89.8% (44/49) of non-cancer individuals and 87.2% (41/47) of gastric cancer patients were accurately classified. CONCLUSIONS: We introduced a liquid biopsy assay using multiple dimensions of cfDNA characteristics that could accurately identify early-stage gastric cancer from non-cancerous conditions. As a cost-effective non-invasive approach, it may provide population-wide benefits for the early detection of gastric cancer. TRIAL REGISTRATION: This study was registered on ClinicalTrials.gov under the identifier NCT05269056 on March 7, 2022.

Spinal myeloid sarcoma presenting as initial symptom in acute promyelocytic leukemia with a rare cryptic PLZF::RARα fusion gene: a case report and literature review.

Background: Acute promyelocytic leukemia (APL) is rarely caused by the PLZF::RARα fusion gene. While APL patients with PLZF::RARα fusion commonly exhibit diverse hematologic symptoms, the presentation of myeloid sarcoma (MS) as an initial manifestation is infrequent. Case presentation: A 61-year-old patient was referred to our hospital with 6-month history of low back pain and difficulty walking. Before this admission, spine magnetic resonance imaging (MRI) conducted at another hospital revealed multiple abnormal signals in the left iliac bone and vertebral bodies spanning the thoracic (T11-T12), lumbar (L1-L4), and sacral (S1/S3) regions. This led to a provisional diagnosis of bone tumors with an unknown cause. On admission, complete blood count (CBC) test and peripheral blood smear revealed a slightly increased counts of monocytes. Immunohistochemical staining of both spinal and bone marrow (BM) biopsy revealed positive expression for CD117, myeloperoxidase (MPO), and lysozyme. BM aspirate showed a significant elevation in the percentage of promyelocytes (21%), which were morphologically characterized by round nuclei and hypergranular cytoplasm. Multiparameter flow cytometry of BM aspirate revealed that blasts were positive for CD13, CD33, CD117, and MPO. Through the integrated application of chromosome analysis, fluorescence in situ hybridization (FISH), reverse transcriptase polymerase chain reaction (RT-PCR), and Sanger sequencing, it was determined that the patient possessed a normal karyotype and a rare cryptic PLZF::RARα fusion gene, confirming the diagnosis of APL. Conclusion: In the present study, we report the clinical features and outcome of a rare APL patient characterized by a cryptic PLZF::RARα fusion and spinal myeloid sarcoma (MS) as the initial presenting symptom. Our study not only offers valuable insights into the heterogeneity of APL clinical manifestations but also emphasizes the crucial need to promptly consider the potential link between APL and MS for ensuring a timely diagnosis and personalized treatments.

Total Syntheses of (±)-Acetoxymarsupellone and (±)-Marsupellins A, B, and D Enabled by a Reductive Cyclization and Semipinacol Rearrangement Strategy.

We report herein the total syntheses of three marsupellin-family sesquiterpenoids, (±)-acetoxymarsupellone and (±)-marsupellins B and D, in 14-19 steps from our known precursor, making marsupellin A also accessible from marsupellin B through a known procedure. The critical tricyclic framework bearing the challenging C7 bridgehead all-carbon quaternary center is strategically constructed through a Ti-mediated reductive cyclization and semipinacol rearrangement sequence. This study provides a general approach to the syntheses of (ent-)longipinane-type molecules.

Mutation characteristics and molecular evolution of ovarian metastasis from gastric cancer and potential biomarkers for paclitaxel treatment.

Ovarian metastasis is one of the major causes of treatment failure in patients with gastric cancer (GC). However, the genomic characteristics of ovarian metastasis in GC remain poorly understood. In this study, we enroll 74 GC patients with ovarian metastasis, with 64 having matched primary and metastatic samples. Here, we show a characterization of the mutation landscape of this disease, alongside an investigation into the molecular heterogeneity and pathway mutation enrichments between synchronous and metachronous metastasis. We classify patients into distinct clonal evolution patterns based on the distribution of mutations in paired samples. Notably, the parallel evolution group exhibits the most favorable prognosis. Additionally, by analyzing the differential response to chemotherapy, we identify potential biomarkers, including SALL4, CCDC105, and CLDN18, for predicting the efficacy of paclitaxel treatment. Furthermore, we validate that CLDN18 fusion mutations improve tumor response to paclitaxel treatment in GC with ovarian metastasis in vitro and vivo.

Sagittal balance parameters measurement on cervical spine MR images based on superpixel segmentation.

Introduction: Magnetic Resonance Imaging (MRI) is essential in diagnosing cervical spondylosis, providing detailed visualization of osseous and soft tissue structures in the cervical spine. However, manual measurements hinder the assessment of cervical spine sagittal balance, leading to time-consuming and error-prone processes. This study presents the Pyramid DBSCAN Simple Linear Iterative Cluster (PDB-SLIC), an automated segmentation algorithm for vertebral bodies in T2-weighted MR images, aiming to streamline sagittal balance assessment for spinal surgeons. Method: PDB-SLIC combines the SLIC superpixel segmentation algorithm with DBSCAN clustering and underwent rigorous testing using an extensive dataset of T2-weighted mid-sagittal MR images from 4,258 patients across ten hospitals in China. The efficacy of PDB-SLIC was compared against other algorithms and networks in terms of superpixel segmentation quality and vertebral body segmentation accuracy. Validation included a comparative analysis of manual and automated measurements of cervical sagittal parameters and scrutiny of PDB-SLIC's measurement stability across diverse hospital settings and MR scanning machines. Result: PDB-SLIC outperforms other algorithms in vertebral body segmentation quality, with high accuracy, recall, and Jaccard index. Minimal error deviation was observed compared to manual measurements, with correlation coefficients exceeding 95%. PDB-SLIC demonstrated commendable performance in processing cervical spine T2-weighted MR images from various hospital settings, MRI machines, and patient demographics. Discussion: The PDB-SLIC algorithm emerges as an accurate, objective, and efficient tool for evaluating cervical spine sagittal balance, providing valuable assistance to spinal surgeons in preoperative assessment, surgical strategy formulation, and prognostic inference. Additionally, it facilitates comprehensive measurement of sagittal balance parameters across diverse patient cohorts, contributing to the establishment of normative standards for cervical spine MR imaging.

Photochemical fate of ß-blocker pindolol in riverine and its downstream coastal waters.

Pindolol (PIN) is a commonly used ß-blocker drug and has been frequently detected in various natural waters. Comprehensive understanding of its environmental photochemical transformation is necessary to assess its environmental risk. In this study, the photodegradation kinetics and mechanisms of PIN in both freshwater and coastal water were investigated for the first time. The photodegradation experiments were carried out by steady-state photochemical experiment under simulated sunlight irradiation. The results showed that the photodegradation rate of PIN in the freshwater of the Pearl River estuary was significantly faster than that in its downstream coastal water. In river water, PIN can undergo both direct photolysis and indirect photolysis induced by riverine dissolved organic matter (DOM) mainly through excited triplet-state of DOM and singlet oxygen, while direct photolysis dominated its degradation in coastal water. The promotion effect was found to be much greater for Suwannee River Natural Organic Matter (SRNOM) than that of the sampled riverine DOM, due to its high steady-state concentrations of reactive species. Interestingly, coastal DOM in northern and southern China were found to have similar promotion effects on PIN photodegradation for the first time, but both less than that of riverine DOM. A total of seven degradation products of PIN resulting from hydroxylation, hydrogen abstraction and cleavage of ether bond were identified. Biological toxicity of one products were found to be higher than that of PIN. These results are of significance for knowing the persistence and ecological risk of PIN in natural waters.

Insights into anthropogenic impact on atmospheric inorganic aerosols in the largest city of the Tibetan Plateau through multidimensional isotope analysis.

Particulate inorganic nitrogen aerosols (PIN) significantly influence air pollution and pose health risks worldwide. Despite extensive observations on ammonium (pNH4+) and nitrate (pNO3-) aerosols in various regions, their key sources and mechanisms in the Tibetan Plateau remain poorly understood. To bridge this gap, this study conducted a sampling campaign in Lhasa, the Tibetan Plateau's largest city, with a focus on analyzing the multiple isotopic signatures (δ15N, ∆17O). These isotopes were integrated into a Bayesian mixing model to quantify the source contributions and oxidation pathways for pNH4+ and pNO3-. Our results showed that traffic was the largest contributor to pNH4+ (31.8 %), followed by livestock (25.4 %), waste (21.8 %), and fertilizer (21.0 %), underscoring the impact of vehicular emissions on urban NH3 levels in Lhasa. For pNO3-, coal combustion emerged as the largest contributor (27.3 %), succeeded by biomass burning (26.3 %), traffic emission (25.3 %), and soil emission (21.1 %). In addition, the ∆17O-based model indicated a dominant role of NO2 + OH (52.9 %) in pNO3- production in Lhasa, which was similar to previous observations. However, it should be noted that the NO3 + volatile organic component (VOC) contributed up to 18.5 % to pNO3- production, which was four times higher than the Tibetan Plateau's background regions. Taken together, the multidimensional isotope analysis performed in this study elucidates the pronounced influence of anthropogenic activities on PIN in the atmospheric environment of Lhasa.

Congener-specific fate and impact of microcystins in the soil-earthworm system.

Microcystins (MCs) have a significant influence on aquatic ecosystems, but little is known about their terrestrial fate and impact. Here, we investigated the fate of two MCs (MC-LR and MC-RR) in the soil-earthworm system, with consideration of their congener-specific impact on earthworm health, soil bacteria, and soil metabolome. Although MCs had little acute lethal effect on earthworms, they caused obvious growth inhibition and setae rupture. Relative to MC-RR, MC-LR exhibited higher bioaccumulation and the resulting dermal lesions and deformation of longitudinal muscles. While the incorporation of both MCs into soils stimulated pathogenic bacteria and depressed oxidative stress tolerant bacteria, the response among soil nitrification and glutathione metabolism differed between the two congeners. The dissipation kinetics of MCs obeyed the first-order model. Earthworms stimulated soil N-cycling enzyme activities, increased the abundance of MC-degrading bacteria, and promoted bacterial metabolic functions related to glutathione metabolism, xenobiotics biodegradation, and metabolism of amino acids that comprise MCs, which accelerated the dissipation of MC-LR and MC-RR by 227% and 82%, respectively. These results provide evidence of significant congener differences in the terrestrial fate and impact of MCs, which will enable a better understanding of their role in mediating soil functions and ecosystem services.

Novel selective agents for the degradation of AR/AR-V7 to treat advanced prostate cancer.

The androgen receptor AR antagonists, such as enzalutamide and apalutamide, are efficient therapeutics for the treatment of prostate cancer (PCa). Even though they are effective at first, resistance to both drugs occurs frequently. Resistance is mainly driven by aberrations of the AR signaling pathway including AR gene amplification and the expression of AR splice variants (e.g. AR-V7). This highlights the urgent need for alternative therapeutic strategies. Here, a total of 24 compounds were synthesized and biologically evaluated to disclose compound 20i, exhibiting potent AR antagonistic activities (IC50 = 172.85 ± 21.33 nM), promising AR/AR-V7 protein degradation potency, and dual targeting site of probably AR (ligand-binding domain, LBD and N-terminal domain, NTD). It potently inhibits cell growth with IC50 values of 4.87 ± 0.52 and 2.07 ± 0.34 µM in the LNCaP and 22RV1 cell lines, respectively, and exhibited effective tumor growth inhibition (TGI = 50.9 %) in the 22RV1 xenograft study. These data suggest that 20i has the potential for development as an AR/AR-V7 inhibitor with degradation ability to treat advanced prostate cancer.

Catheter-guided anvil insertion for circular stapler esophagojejunal anastomosis: a novel technique in laparoscopic total gastrectomy.

OBJECTIVE: This study evaluates feasibility, safety, and short-term outcomes of employing the catheter-guided stapler anvil insertion technique for esophagojejunal anastomosis using a circular stapler during laparoscopic total gastrectomy (LTG). MATERIALS AND METHODS: From September 2021 to April 2023, the catheter-guided stapler anvil insertion technique was employed in 80 patients undergoing laparoscopic total gastrectomy (LTG) for esophagojejunal anastomosis. A modified D2 dissection, according to the en bloc technique, was performed in the patients. Subsequently, a longitudinal incision, approximately 2 cm in length, was made on the anterior wall of the esophagus, about 2 cm above the tumor. The transection line was pre-marked with blue dye along the esophagus's minor axis, and the tail of the anvil was capped with a 10-cm length of catheter (F14 d4.7 mm). The surgeon secures the head of anvil and carefully inserts it into the esophagus, ensuring that only a 5-cm segment of the catheter remains outside the esophagus. A linear cutter was employed to transect and seal the lower end of the esophagus. Subsequently, esophagojejunostomy was performed under laparoscopic guidance using a circular stapler. RESULTS: Among patients undergoing esophagojejunal anastomosis with the new technique, postoperative complications included pneumonia or pleural effusion in 14 patients (17.5%), anastomotic stenosis in 3 patients (3.75%), abdominal infection in 2 patients (2.5%), and intestinal obstruction in 1 patient (1.25%). No instances of anastomotic leakage, anastomotic bleeding, or deaths were recorded. All patients experiencing complications improved with conservative treatment, without the need for secondary surgery. CONCLUSION: The catheter-guided stapler anvil insertion technique is demonstrated to be a safe and effective method for esophagojejunostomy, potentially reducing the occurrence of anastomotic leakage.

Clinicopathological characteristics of gastric neuroendocrine neoplasms: A comprehensive analysis.

OBJECTIVE: This study aimed to explore the clinicopathological characteristics and prognostic implications of gastric neuroendocrine neoplasms (g-NENs). METHODS: A retrospective enrollment of 142 patients diagnosed with g-NENs was conducted at Zhejiang Cancer Hospital between January 1, 2007 and December 31, 2021. The study compared essential clinicopathological features and survival rates. Additionally, the prognosis of gastric neuroendocrine carcinomas/mixed neuroendocrine-non-neuroendocrine neoplasms (g-NEC/MiNEN) were contrasted with those of gastric adenocarcinoma (GAC) and signet ring cell carcinoma (SRCC). RESULTS: The study comprised a total of 142 g-NENs cases, with a male-to-female ratio of approximately 2:1. The 5-year survival rates for g-NEC and g-MiNEN were 26.7% and 35.2%, respectively. Corresponding 5-year survival rates for G1 and G2 were observed at 100% and 80.0%, respectively. g-NEC/MiNEN showed a significantly worse prognosis compared to g-NET (p < 0.001). g-NEC/MiNEN exhibited a poor prognosis compared to GAC (p < 0.001), and within poorly differentiated GAC, g-NEC/MiNEN demonstrated a worse prognosis (p = 0.007). Additionally, patients receiving postoperative adjuvant therapy exhibited notably prolonged overall survival (OS) in the case of g-NEC/MiNEN (p = 0.010). CONCLUSION: In short, the prognosis of g-NEC/MiNEN was worse than that of g-NET, GAC and poorly differentiated GAC, but this group benefit from postoperative adjuvant therapy.

Genomic and immune microenvironment features influencing chemoimmunotherapy response in gastric cancer with peritoneal metastasis: a retrospective cohort study.

BACKGROUND: Patients with peritoneal metastasis (PM) from gastric cancer (GC) exhibit poor prognosis. Chemoimmunotherapy offers promising clinical benefits; however, its efficacy and predictive biomarkers in a conversion therapy setting remain unclear. The authors aimed to retrospectively evaluate chemoimmunotherapy efficacy in a conversion therapy setting for GC patients with PM and establish a prediction model for assessing clinical benefits. MATERIALS AND METHODS: A retrospective evaluation of clinical outcomes encompassed 55 GC patients with PM who underwent chemoimmunotherapy in a conversion therapy setting. Baseline PM specimens were collected for genomic and transcriptomic profiling. Clinicopathological factors, gene signatures, and tumor immune microenvironment were evaluated to identify predictive markers and develop a prediction model. RESULTS: Chemoimmunotherapy achieved a 41.8% objective response rate and 72.4% R0 resection rate in GC patients with PM. Patients with conversion surgery showed better overall survival (OS) than those without the surgery (median OS: not reached vs 7.82 m, P <0.0001). Responders to chemoimmunotherapy showed higher ERBB2 and ERBB3 mutation frequencies, CTLA4 and HLA-DQB1 expression, and CD8+ T cell infiltration, but lower CDH1 mutation and naïve CD4+ T cell infiltration, compared to nonresponders. A prediction model was established integrating CDH1 and ERBB3 mutations, HLA-DQB1 expression, and naïve CD4+ T cell infiltration (AUC=0.918), which were further tested using an independent external cohort (AUC=0.785). CONCLUSION: This exploratory study comprehensively evaluated clinicopathological, genomic, and immune features and developed a novel prediction model, providing a rational basis for the selection of GC patients with PM for chemoimmunotherapy-involved conversion therapy.

Dynamical evolution of CO2 and H2O on garnet electrolyte elucidated by ambient pressure X-ray spectroscopies.

Garnet-type Li6.5La3Zr1.5Ta0.5O12 (LLZO) is considered a promising solid electrolyte, but the surface degradation in air hinders its application for all-solid-state battery. Recent studies have mainly focused on the final products of the LLZO surface reactions due to lacking of powerful in situ characterization methods. Here, we use ambient pressure X-ray spectroscopies to in situ investigate the dynamical evolution of LLZO surface in different gas environments. The newly developed ambient pressure mapping of resonant Auger spectroscopy clearly distinguishes the lithium containing species, including LiOH, Li2O, Li2CO3 and lattice oxygen. The reaction of CO2 with LLZO to form Li2CO3 is found to be a thermodynamically favored self-limiting reaction. On the contrary, the reaction of H2O with LLZO lags behind that of CO2, but intensifies at high pressure. More interestingly, the results provide direct spectroscopic evidence for the existence of Li+/H+ exchange and reveal the importance of the initial layer formed on clean electrolyte surface in determining their air stability. This work demonstrates that the newly developed in situ technologies pave a new way to investigate the oxygen evolution and surface degradation mechanism in energy materials.

Physiological and Molecular Response of Liriodendron chinense to Varying Stand Density.

Stand density affects the potentially superior productivity of forest ecosystems directly by regulating the light and nutrient availability of trees. Understanding how stand density influences the growth and development of trees is crucial for supporting forest management in the context of climate change. We focused on Liriodendron chinense in experimental plantations created in 2003, with planting densities ranging from 277 to 10,000 trees per hectare at six plots. The leaf structure and photosynthetic capacity of L. chinense changed significantly under different stand densities, which had a negative impact on their biomass (leaf mass) and nutrient (total carbohydrate content) accumulation. Transcriptional differences were observed among samples from plots with different planting densities. The expression of 1784 genes was negatively dependent on stand density, participating mainly in the biological processes of "circadian rhythm", "carbon metabolism", and "amino acid biosynthesis". Furthermore, we identified a photosynthesis-related module and constructed a gene regulatory network to discover that the transcription factors of MYB and bHLH may have important roles in the transcriptional regulation of photosynthesis biosynthesis by activating or repressing the expression of petA (Litul.15G096200), psbE (Litul.10G033900), and petD (Litul.17G061600) at different stand densities. Our study quantified the impact of stand density on tree growth at physiological and molecular levels. Our observations provide theoretical support for plantation establishment of L. chinense.