Undescribed steroidal alkaloids from the bulbs of Fritillaria ussuriensis Maxim and their anti-inflammatory activities.

In total, 16 undescribed steroidal alkaloids (1-16), along with nine known ones (17-25), were isolated from the bulbs of Fritillaria ussuriensis Maxim. Among the undescribed compounds mentioned, compounds 1-6, 8 bearing an 16ß-hydroxy substituent, as well as compounds 13 and 14 exhibited an unusual seven-membered skeleton. Their structures were established based on extensive spectroscopic analyses, including HRESIMS and NMR (1D and 2D), and comparison with the data reported in the literature. Furthermore, all the compounds were evaluated for their anti-inflammatory effect on the NO production of LPS-stimulated RAW264.7 cells. Compounds 1, 4, 11, 15, 22 and 24 could significantly inhibit NO production with IC50 values below 10 µM.

Association of inflammatory trajectory with subarachnoid hemorrhage mortality.

OBJECTIVE: White blood cells (WBC) play an important role in the inflammatory response of the body. Elevated WBC counts on admission in patients with subarachnoid hemorrhage (SAH) correlate with a poor prognosis. However, the role of longitudinal WBC trajectories based on repeated WBC measurements during hospitalization remains unclear. We explored the association between different WBC trajectory patterns and in-hospital mortality. METHODS: We analyzed a cohort of consecutive patients with SAH between 2012 and 2020. Group-based trajectory modeling (GBTM) was used to group the patients according to their white blood cell patterns over the first 4 days. Stabilized inverse probability treatment weighting (sIPTW) was used to balance baseline demographic and clinical characteristics. We analyzed the association between the WBC trajectory groups and in-hospital mortality using a Cox proportional hazards model. RESULTS: In total, 506 patients with SAH were included in this retrospective cohort. The final model identified two distinct longitudinal WBC trajectories. After adjusting for confounding factors, multivariate regression analysis suggested that an elevated longitudinal WBC trajectory increased the risk of in-hospital mortality (hazard ratio [HR], 2.476; 95% confidence interval [CI] 1.081-5.227; P = 0.024) before sIPTW, and (HR, 2.472; 95%CI 1.489-4.977; P = 0.018) after sIPTW. CONCLUSION: In patients with SAH, different clinically relevant groups could be identified using WBC trajectory analysis. The WBC count trajectory-initially elevated and then decreased- may lead to an increased risk of in-hospital mortality following SAH.

Enhancing the selectivity for light olefins through catalytic cracking of n-hexane by phosphorus doping on lanthanum-modified ZSM-5.

Naphtha, as the primary raw material in the production of light olefins, could well accommodate their increasing demand through the energy-efficient process of catalytic cracking with ZSM-5. In the current work, different amounts of lanthanum and phosphorous were loaded on ZSM-5 using the wet impregnation method to tune the acidic properties of ZSM-5 for selective catalytic cracking of n-hexane to produce light olefins. Various characterization techniques such as X-ray diffraction (XRD), Al nuclear magnetic resonance (NMR), temperature-programmed desorption of NH3 (NH3-TPD), Py-Fourier transform infra-red (Py-FTIR), inductively coupled plasma optical emission spectroscopy (ICP-OES), N2 adsorption-desorption, X-ray photoelectron spectra (XPS), and scanning electron microscopy were adopted to investigate the modified zeolites. It was found that adding La to ZSM-5 (0.25 wt% to 1 wt%) improved the catalytic life and increased the n-hexane conversion (to 99.7%), while the further addition had a negative impact, reducing the conversion rate and deviating the product selectivity towards a substantial, undesired benzene, toluene, and xylene (BTX) fraction (33%). On the other hand, a 64% selectivity for light olefins was achieved on phosphorous-doped ZSM-5 (at a loading amount of 1 wt%) while reducing the BTX fraction (2.3%) and converting 69% of the n-hexane. A dual metal-modified ZSM-5 with optimal loading amount, 1P0.25LaZ5 (phosphorus 1 wt% and La 0.25 wt%), helped boost the light olefin selectivity to 62% in the tuned Lewis acid sites at an n-hexane conversion of about 77% while decreasing the undesired BTX selectivity to 3% by reducing the number of Brønsted sites. Thus, the current study reveals that tuning the acidic sites of ZMS-5 by dual metal augmentation with P.La is an effective way of controlling the amount of undesirable BTX produced at a stable n-hexane conversion rate and substantial olefin selectivity.

Non-Clinical Safety Evaluation of Exosomes Derived from Human Umbilical Cord Mesenchymal Stem Cells in Cynomolgus Monkeys.

Purpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future. Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection. Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group. Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.

Decoupling the correlation between cytotoxic and exhausted T lymphocyte states enhances melanoma immunotherapy response prediction.

Cytotoxic T lymphocyte (CTL) and terminal exhausted T lymphocyte (ETL) activities crucially influence immune checkpoint inhibitor (ICI) response. Despite this, the efficacy of ETL and CTL transcriptomic signatures for response prediction remains limited. Investigating this across the TCGA and publicly available single-cell cohorts, we find a strong positive correlation between ETL and CTL expression signatures in most cancers. We hence posited that their limited predictability arises due to their mutually canceling effects on ICI response. Thus, we developed DETACH, a computational method to identify a gene set whose expression pinpoints to a subset of melanoma patients where the CTL and ETL correlation is low. DETACH enhances CTL's prediction accuracy, outperforming existing signatures. DETACH signature genes activity also demonstrates a positive correlation with lymphocyte infiltration and the prevalence of reactive T cells in the tumor microenvironment (TME), advancing our understanding of the CTL cell state within the TME.

A case report of the treatment of carotid artery stenosis by staged angioplasty based on intraoperative TCD monitoring.

Objective: Cerebral hyperperfusion syndrome (CHS) is the most severe complication of carotid artery stenting (CAS) or endarterectomy (CEA). Staging treatment can effectively reduce the risk of CHS without increasing the risk of ischemic stroke. The first stage of balloon dilatation is critical for staged treatment. However, the successful criterion of the first stage balloon dilatation is still inconsistent. Method: In the current study presents a case of a 61-year-old male with bilateral internal carotid subtotal occlusion, transcranial doppler (TCD) was used to measure middle cerebral artery (MCA) flow rate on the narrow side of surgery and the results are promising. Result: Intraoperative TCD monitoring is expected to be an evaluation criterion for staged angioplasty for carotid artery stenosis. Conclusion: The approach of blood flow velocity in the brain based on intraoperative measurement of TCD during the treatment of this patient is a new idea for staging treatment in the future.

The prognostic value of co-expression of stemness markers CD44 and CD133 in endometrial cancer.

Objective: The purpose of this study was to investigate the correlation between stemness markers (CD44 and CD133) and clinical pathological features, and to further explore the prognostic value of co-expression of CD44 & CD133 in endometrial cancer (EC). Methods: Clinical data of stage I-III EC patients who underwent initial surgical treatment at two large tertiary medical centers from 2015 to 2020 were retrospectively collected. Cohen's kappa coefficient was used to show the consistency of the expression between CD44 and CD133. The correlation between co-expression of CD44 & CD133 and prognosis of EC patients was explored using univariate and multivariate Cox regression analysis. Then, the prognosis models for early-stage (stage I-II) EC patients were constructed. Finally, stratified analysis was performed for EC patients in high-intermediate-risk and high-risk groups, Kaplan-Meier analysis was used to compare the survival differences between patients with and without adjuvant therapy in different co-expression states (low expression, mixed expression, high expression) of CD44 & CD133. Results: A total of 1168 EC patients were included in this study. The consistency of the expression between CD44 and CD133 was 70.5%, the kappa coefficient was 0.384. High expression of CD44 & CD133 was associated with early FIGO stage (P=0.017), superficial myometrial invasion (P=0.017), and negative lymphatic vessel space invasion (P=0.017). Cox regression analysis showed that the co-expression of CD44 & CD133 was significantly correlated with the prognosis of early-stage (stage I-II) patients (P=0.001 for recurrence and P=0.005 for death). Based on this, the nomogram models were successfully constructed to predict the prognosis of early-stage EC patients. Meanwhile, Kaplan-Meier analysis showed that patients with adjuvant therapy had a better overall prognosis than those without adjuvant therapy in high-intermediate-risk and high-risk groups. However, there was no statistically significant difference in survival between patients with and without adjuvant therapy in high expression of CD44 & CD133 group (P=0.681 for recurrence, P=0.621 for death). Conclusion: High expression of CD44 & CD133 was closely related to the adverse prognosis of early-stage EC patients. Meanwhile, patients with high expression of CD44 & CD133 may not be able to achieve significant survival benefits from adjuvant therapy.

CAR T Cell Membrane Camouflaged Nanocatalyst Augments CAR T Cell Therapy Efficacy Against Solid Tumor.

The immunosuppressive tumor microenvironment (TME) reduces the chimeric antigen receptor (CAR) T-cell therapy against solid tumors. Here, a CAR T cell membrane-camouflaged nanocatalyst (ACSP@TCM) is prepared to augment CAR T cell therapy efficacy against solid tumors. ACSP@TCM is prepared by encapsulating core/shell Au/Cu2- xSe and 3-bromopyruvate with a CAR T cell membrane. It is demonstrated that the CAR T cell membrane camouflaging has much better-targeting effect than the homologous tumors cell membrane camouflaging. ACSP@TCM has an appealing synergistic chemodynamic/photothermal therapy (CDT/PTT) effect that can induce the immunogenic cell death (ICD) of NALM 6 cells. Moreover, 3-bromopyruvate can inhibit the efflux of lactic acid by inhibiting the glycolysis process, regulating the acidity of TME, and providing a more favorable environment for the survival of CAR T cells. In addition, the photoacoustic (PA) imaging and computed tomography (CT) imaging performance can guide the ACSP@TCM-mediated tumor therapy. The results demonstrated that the ACSP@TCM significantly enhanced the CAR T cell therapy efficacy against NALM 6 solid tumor mass, and completely eliminated tumors. This work provides an effective tumor strategy for CAR T cell therapy in solid tumors.

Improving grape fruit quality through soil conditioner: Insights from RNA-seq analysis of Cabernet Sauvignon roots.

The application of fertilizers and soil quality are crucial for grape fruit quality. However, the molecular data linking different fertilizer (or soil conditioner [SC]) treatments with grape fruit quality is still lacking. In this study, we investigated three soil treatments, namely inorganic fertilizer (NPK, 343.5 kg/hm2 urea [N ≥ 46%]; 166.5 kg/hm2 P2O5 [P2O5 ≥ 64%]; 318 kg/hm2 K2O [K2O ≥ 50%]), organic fertilizer (Org, 9 t/hm2 [organic matter content ≥ 35%, N + P2O5 + K2O ≥ 13%]), and SC (SC, 3 t/hm2 [humic acid ≥ 38.5%; C, 56.1%; H, 3.7%; N, 1.5%; O, 38%; S, 0.6%]), on 4-year-old Cabernet Sauvignon grapevines. Compared with the NPK- and Org-treated groups, the SC significantly improved the levels of soluble solids, tannins, anthocyanins, and total phenols in the grape berries, which are important biochemical indicators that affect wine quality. Furthermore, we conducted RNA-seq analysis on the grapevine roots from each of the three treatments and used weighted gene co-expression network analysis to identify five hub genes that were associated with the biochemical indicators of the grape berries. Furthermore, we validated the expression levels of three hub genes (ERF, JP, and SF3B) and five selected genes related to anthocyanin biosynthesis (UFGT1, UFGT2, UFGT3, GST, and AT) by using quantitative reverse transcription-polymerase chain reaction. Compared to the NPK and Org treatment groups, the SC treatment resulted in a significant increase in the transcription levels of three hub genes as well as VvUFGT1, VvUFGT3, VvGST, and VvAT. These results suggest that the SC can improve grape fruit quality by altering gene transcription patterns in grapevine roots and further influence the biochemical indices of grape fruits, particularly anthocyanin content. This study reveals that the application of SC can serve as an important measure for enhancing vineyard SC and elevating grape quality.

Efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in the treatment of locally advanced cervical cancer.

BACKGROUND: Evaluate the efficacy and safety of different chemotherapy regimens concurrent with radiotherapy in treating locally advanced cervical cancer (LACC). METHODS: Retrospective data was collected from LACC patients who were treated at our institution. These patients were categorized into three groups: the single-agent cisplatin (DDP) chemoradiotherapy group, the paclitaxel plus cisplatin (TP) chemoradiotherapy group, and the nanoparticle albumin-bound (nab-) paclitaxel combined with cisplatin (nPP) chemoradiotherapy group. The primary endpoints were overall survival (OS) and progression-free survival (PFS) and the secondary endpoints were objective response rate (ORR) and incidence of adverse events (AEs). RESULTS: A total of 124 patients were enrolled (32 in the DDP group, 41 in the TP group, and 51 in the nPP group). There were differences in OS (P = 0.041, HR 0.527, 95% CI 0.314-0.884) and PFS (P = 0.003, HR 0.517, 95% CI 0.343-0.779) between the three groups. Notably, the 2-year OS rate was significantly higher in the nPP group compared to the DDP group (92.2% vs. 85.4%, P = 0.012). The 2-year PFS rates showed a marked increase in the TP group (78.0% vs. 59.4%, P = 0.048) and the nPP group (88.2% vs. 59.4%, P = 0.001) relative to the DPP group, with multiple comparisons indicating that the 2-year PFS rate was significantly superior in the nPP group versus the DDP group (88.2% vs. 59.4%, P = 0.001). Moreover, the ORR was also significantly higher in the nPP group than in the DDP group (P = 0.013); and no statistically significant differences were found in the incidence of AEs among the groups (P > 0.05). CONCLUSIONS: In LACC treatment, the two cisplatin-based doublet chemotherapy regimens are associated with better outcomes, with the nab-paclitaxel plus cisplatin regimen showing better efficacy than the paclitaxel plus cisplatin regimen. Furthermore, the AEs associated with these regimens were deemed tolerable. These findings could provide a reference for the clinical treatment of LACC. However, further prospective studies are needed to verify it.

Novel strategy to quantify the viability of oocysts of Cryptosporidium parvum and C. hominis, a risk factor of the waterborne protozoan pathogens of public health concern.

While waters might be contaminated by oocysts from >40 Cryptosporidium species, only viable oocysts of C. parvum and C. hominis truly pose the main health risk to the immunocompetent population. Oocyst viability is also an important but often neglected risk factor in monitoring waterborne parasites. However, commonly used methods in water monitoring and surveys cannot distinguish species (microscopic observation) or oocyst viability (PCR), as dead oocysts in water could retain gross structure and DNA content for weeks to months. Here, we report new TaqMan qRT-PCR/qPCR assays for quantitative detection of viable C. parvum and C. hominis oocysts. By targeting a hypothetical protein-encoding gene cgd6_3920 that is highly expressed in oocysts and variable between species, the qRT-PCR/qPCR assays achieve excellent analytical specificity and sensitivity (limit of quantification [LOQ] = 0.25 and 1.0 oocyst/reaction). Using calibration curves, the number and ratio of viable oocysts in specimens could be calculated. Additionally, we also establish a TaqMan-18S qPCR for cost-effective screening of pan-Cryptosporidium-positive specimens (LOQ = 0.1 oocyst/reaction). The assay feasibility is validated using field water (N = 43) and soil (79) specimens from 17 locations in Changchun, China, which detects four Cryptosporidium species from seven locations, including three gp60-subtypes (i.e., IIdA19G1, IIdA17G1 and IIdA24G2) of C. parvum oocysts showing varied viability ratios. These new TaqMan q(RT)-PCR assays supplement current methods in the survey of waters and other samples (e.g., surfaces, foods and beverages), and are applicable to assessing the efficiency of oocyst deactivation protocols.

Understanding the Relationship Between Vascular Smooth Muscle Cell Function and the Efficacy of Acupuncture in Treating Cerebral Ischemic Stroke: A Preclinical Meta-Analysis and Systematic Review.

Background: Cerebral blood flow and vascular structures serve as the fundamental components of brain metabolism and circulation. Acupuncture, an alternative and complementary medical approach, has demonstrated efficacy in treating cerebral ischemic stroke (CIS). Nevertheless, the mechanisms underlying the impact of acupuncture on vascular smooth muscle cell (VSMC) function remain uncertain. The objective of this systematic review and meta-analysis is to assess the alterations in VSMC function following acupuncture stimulation in CIS models. Methods: The databases PubMed, Web of Science, SCOPUS, and EMBASE were queried until November 2022 using a predetermined search strategy. The FORMAT BY SYRCLE guidelines were adhered to, and the risk of bias of the included studies was evaluated using the Risk of Bias tool developed by the Systematic Review Centre for Laboratory Animal Experimentation. The random-effects model was employed to estimate the standardized mean difference (SMD). Results: Eighteen articles are included in this review. Acupuncture showed significant positive effects on the region cerebral blood flow (SMD=8.15 [95% CI, 4.52 to 11.78]) and neurological deficiency (SMD=-3.75 [95% CI, -5.54 to -1.97]). Descriptive analysis showed a probable mechanism of acupuncture stimulation in CIS rats related to VSMC function. Limitations and publication bias were presented in the studies. Conclusion: In this systematic review and meta-analysis, our findings indicate that acupuncture stimulation has the potential to improve regional cerebral blood flow and alleviate neurological deficits, possibly by regulating VSMC function. However, it is important to exercise caution when interpreting these results due to the limitations of animal experimental design and methodological quality.

A novel perineal exposure method in laparoscopic abdominal perineal resection of rectal cancer: a case series study.

BACKGROUND: Abdominal perineal resection (APR) of rectal cancer, also known as Mile's procedure, is a classic procedure for the treatment of rectal cancer. Through the improvement of surgical skills and neoadjuvant therapy, the sphincter-preserving rate in rectal cancer patients has improved, even in patients with ultralow rectal cancer who underwent APR in the past. However, APR cannot be completely replaced by low anterior resection (LAR) in reality. APR still has its indications, when the tumor affects the external sphincter, etc. Good perineal exposure in APR is difficult and can seriously affect surgical safety and the long-term prognosis. METHODS: We reviewed the records of 16 consecutive patients with rectal cancer who underwent APR at Anqing Municipal Hospital from January 2022 to April 2023, including 11 males and 5 females, with an average age of 64.8 ± 10.3 years. The perineal operation was completed with the Lone-Star® retractor-assisted (LSRA) exposure method. After incising the skin and subcutaneous tissue, a Lone-Star® retractor was placed, and the incision was retracted in surrounding directions with 8 small retractors, which facilitated the freeing of deep tissues. We dynamically adjusted the retractor according to the plane to fully expose the surgical field. RESULTS: All 16 patients underwent laparoscopic-assisted APR successfully. Thirteen procedures were performed independently by a single person, and the others were completed by two persons due to intraoperative arterial hemostasis. All specimens were free of perforation and had a negative circumferential resection margin (CRM). Postoperative complications occurred in 4 patients, including urinary retention in 1 patient, pulmonary infection in 1 patient, intestinal adhesion in 1 patient and peristomal dermatitis in 1 patient, and were graded as ClavienDindo grade 3 or lower and cured. No distant metastasis or local recurrence was found for any of the patients in the postoperative follow-up. CONCLUSIONS: The application of the LSRA exposure method might be helpful for perineal exposure during APR for rectal cancer, which could improve intraoperative safety and surgical efficiency, achieve one-person operation, and increase the comfort of operators.

Effects of low protein feed on hepato-intestinal health and muscle quality of grass carp (Ctenopharyngodon idellus).

In this study, grass carp (33.28 ± 0.05 g) were fed three diets for 8 weeks: control (crude protein [CP] 30%, crude lipid [CL] 6%), low protein (LP; CP16%, CL6%), and low protein with high-fat (LPHF; CP16%, CL10%). The final body weight decreased in the LP and LPHF groups compared to the Control (P < 0.05). Liver triglycerides, total cholesterol, and nonesterified fatty acids were higher in the LP group than the Control, whereas these indexes in the LPHF group were higher than those in the LP group (P < 0.05). The LP group had intestinal barrier damage, while the LPHF group had a slight recovery. TNF-α, IL-8, and IL-1ß content were lower in the LP group than in the Control (P < 0.05), and even higher in the LPHF group (P < 0.05). The expressions of endoplasmic reticulum stress-related genes Activating transcription factor 6 (ATF-6) and Glucose-regulated protein (GRP78) were higher in the LPHF group against the LP group (P < 0.05). The IL-1ß and TNF-α content negatively correlated with intestinal Actinomycetes and Mycobacterium abundance (P < 0.05). The muscle fiber diameter was smaller in both the LP and LPHF groups than the control (P < 0.05), with the LP group showing metabolites related to protein digestion and absorption, and LPHF group exhibiting metabolites related to taste transmission. The results demonstrate reducing dietary protein affects growth, causing liver lipid accumulation, reduced enteritis response, and increased muscle tightness, while increasing fat content accelerates fat accumulation and inflammation.

Moringin alleviates DSS-induced ulcerative colitis in mice by regulating Nrf2/NF-κB pathway and PI3K/AKT/mTOR pathway.

Ulcerative colitis (UC) is a main form of inflammatory bowel disease (IBD), which is a chronic and immune-mediated inflammatory disease. Moringin (MOR) is an isothiocyanate isolated from Moringa oleifera Lam., and has been recognized as a promising potent drug for inflammatory diseases and antibacterial infections. The present study investigated the role of moringin in dextran sulfate sodium (DSS)-induced UC mice. Mouse colitis was induced by adding DSS to the drinking water for seven consecutive days. Our experimental results showed that MOR relieves DSS-induced UC in mice by increasing body weight and colonic length, and reducing the disease activity index and histological injury. Mechanistically, MOR improves intestinal barrier function by increasing the expression of tight junction proteins (TJPs) and enhancing the secretion of mucin in DSS-induced mice. MOR inhibits inflammatory response and intestinal damage by regulating Nrf2/NF-κB signaling pathway and modulating the PI3K/AKT/mTOR pathway. Furthermore, in Nrf2 knockout (Nrf2-/-) mice, the protective effects of MOR on DSS-induced UC were abolished. Meanwhile, treatment with MOR reduced inflammation and cell damage via regulating Nrf2/NF-κB pathway in a lipopolysaccharide (LPS)-induced inflammation model of Caco-2 cells. In contrast, ML385, an Nrf2 inhibitor, might eliminate the protection provided by MOR. Notably, treatment with MOR significantly up-regulated the expression of peroxisome proliferator-activated receptor-γ (PPAR-γ), suggesting that MOR may be a potential PPAR-γ activator. In conclusion, MOR exerts protective effect in UC by improving intestinal barrier function, regulating Nrf2/NF-κB and PI3K/AKT/mTOR signaling pathways, and another effect associated with the regulation of PPAR-γ expression.

Metabolism-inflammasome crosstalk shapes innate and adaptive immunity.

Inflammasomes are a central component of innate immunity and play a vital role in regulating innate immune response. Activation of inflammasomes is also indispensable for adaptive immunity, modulating the development and response of adaptive immunity. Recently, increasing studies have shown that metabolic alterations and adaptations strongly influence and regulate the differentiation and function of the immune system. In this review, we will take a holistic view of how inflammasomes bridge innate and adaptive (especially T cell) immunity and how inflammasomes crosstalk with metabolic signals during the immune responses. And, special attention will be paid to the metabolic control of inflammasome-mediated interactions between innate and adaptive immunity in disease. Understanding the metabolic regulatory functions of inflammasomes would provide new insights into future research directions in this area and may help to identify potential targets for inflammasome-associated diseases and broaden therapeutic avenues.

Triterpenoids from the leaves of Eleutherococcus sessiliflorus, and their antiproliferative activities in TNF-α induced HFLS-RA cells.

Five undescribed elesesterpenes L-U, along with nine known 3,4-seco-lupane-type triterpenoids were isolated from the leaves of Eleutherococcus sessiliflorus (Rupr. & Maxim.) S. Y. Hu. Elesesterpene L-S, and U were lupane-type triterpenoids, whereas elesesterpene T was an oleanane-type triterpenoid, probably artifact, as suggested by LC-MS analysis. Out of the nine known compounds, five were initially identified in E. sessiliflorus. Moreover, their structures were definitively determined using spectroscopic analyses, and the absolute configurations of elesesterpenes L-M and sachunogenin 3-O-glucoside were clarified using X-ray crystallographic techniques. The absolute configuration of elesesterpene T was determined by measuring and calculating its ECD. In addition, all compounds were tested to examine their ability to inhibit the proliferation of HFLS-RA cells induced by TNF-α in vitro. Elesesterpene M, chiisanogenin, chiisanoside, and 3-methylisochiisanoside significantly inhibited HFLS-RA proliferation.

A novel multilevel iterative training strategy for the ResNet50 based mitotic cell classifier.

The number of mitotic cells is an important indicator of grading invasive breast cancer. It is very challenging for pathologists to identify and count mitotic cells in pathological sections with naked eyes under the microscope. Therefore, many computational models for the automatic identification of mitotic cells based on machine learning, especially deep learning, have been proposed. However, converging to the local optimal solution is one of the main problems in model training. In this paper, we proposed a novel multilevel iterative training strategy to address the problem. To evaluate the proposed training strategy, we constructed the mitotic cell classification model with ResNet50 and trained the model with different training strategies. The results showed that the models trained with the proposed training strategy performed better than those trained with the conventional strategy in the independent test set, illustrating the effectiveness of the new training strategy. Furthermore, after training with our proposed strategy, the ResNet50 model with Adam optimizer has achieved 89.26% F1 score on the public MITOSI14 dataset, which is higher than that of the state-of-the-art methods reported in the literature.

Mandibular Osteomyelitis as the Earliest Clinical Manifestation of Maxillary Sinus Lymphoma.

Extranodal natural killer/T-cell lymphoma is a distinct subtype of non-Hodgkin lymphoma that originates from natural killer cells or cytotoxic T cells. Its diagnosis is challenging due to the rarity and lack of awareness, especially in cases where osteomyelitis of the jawbone is the initial symptom. This paper reports a case of extranodal natural killer/T-cell lymphoma presenting primarily with oral ulcers. Through analyzing the clinical and pathological characteristics, differential diagnosis, treatment and prognosis, and reasons for misdiagnosis of the disease, this study aims to provide references for clinical diagnosis and treatment.

Electrostatic doping tunable magnetic transition and half-metallicity in the monolayer CrCTe3.

The electrical manipulation of the magnetic transition and spin-polarized states has attracted extensive attention in the field of spintronics. In this work, we perform a detailed study on the electronic and magnetic properties of the carrier-doped monolayer CrCTe3by using first-principles calculation. It is found that, the magnetic transition from Néel-antiferomagnetic (nAFM) to ferromagnetic (FM) is observed in the case of the electron doping, while for hole doping a magnetic transition sequence of nAFM→zigzag-AFM→FM is observed in the monolayer CrCTe3. Interestingly, the carrier doping induced FM ground state always exhibits half-metallicity with full spin polarization. Moreover, the spin polarity of the half-metallic electronic states is opposite for electron and hole doping, meaning that the spin polarization direction can be tuned by manipulating a gate voltage. The Monte Carlo calculations show that the magnetic transition temperature of the doped FM CrCTe3is rapidly increased with the increasing doping concentration and is extremely expected to achieve room temperature at a suitable doping concentration. These findings demonstrate that the monolayer AFM system possesses a potential application in spintronic devices with electrically tunable spin polarization.