Multi-level sequence denoising with cross-signal contrastive learning for sequential recommendation.

Sequential recommender systems (SRSs) aim to suggest next item for a user based on her historical interaction sequences. Recently, many research efforts have been devoted to attenuate the influence of noisy items in sequences by either assigning them with lower attention weights or discarding them directly. The major limitation of these methods is that the former would still prone to overfit noisy items while the latter may overlook informative items. To the end, in this paper, we propose a novel model named Multi-level Sequence Denoising with Cross-signal Contrastive Learning (MSDCCL) for sequential recommendation. To be specific, we first introduce a target-aware user interest extractor to simultaneously capture users' long and short term interest with the guidance of target items. Then, we develop a multi-level sequence denoising module to alleviate the impact of noisy items by employing both soft and hard signal denoising strategies. Additionally, we extend existing curriculum learning by simulating the learning pattern of human beings. It is worth noting that our proposed model can be seamlessly integrated with a majority of existing recommendation models and significantly boost their effectiveness. Experimental studies on five public datasets are conducted and the results demonstrate that the proposed MSDCCL is superior to the state-of-the-art baselines. The source code is publicly available at https://github.com/lalunex/MSDCCL/tree/main.

Icariin attenuates asthmatic airway inflammation via modulating alveolar macrophage activation based on network pharmacology and in vivo experiments.

BACKGROUND: Icariin (ICA) inhibits inflammatory response in various diseases, but the mechanism underlying ICA treating airway inflammation in asthma needs further understood. We aimed to predict and validate the potential targets of ICA against asthma-associated airway inflammation using network pharmacology and experiments. METHODS: The ovalbumin-induced asthma-associated airway inflammation mice model was established. The effects of ICA were evaluated by behavioral, airway hyperresponsiveness, lung pathological changes, inflammatory cell and cytokines counts. Next, the corresponding targets of ICA were mined via the SEA, CTD, HERB, PharmMapper, Symmap database and the literature. Pubmed-Gene and GeneCards databases were used to screen asthma and airway inflammation-related targets. The overlapping targets were used to build an interaction network, analyze gene ontology and enrich pathways. Subsequently, flow cytometry, quantitative real-time PCR and western blotting were employed for validation. RESULTS: ICA alleviated the airway inflammation of asthma; 402 targets of ICA, 5136 targets of asthma and 4531 targets of airway inflammation were screened; 216 overlapping targets were matched and predicted ICA possesses the potential to modulate asthmatic airway inflammation by macrophage activation/polarization. Additionally, ICA decreased M1 but elevated M2. Potential targets that were disrupted by asthma inflammation were restored by ICA treatment. CONCLUSIONS: ICA alleviates airway inflammation in asthma by inhibiting the M1 polarization of alveolar macrophages, which is related to metabolic reprogramming. Jun, Jak2, Syk, Tnf, Aldh2, Aldh9a1, Nos1, Nos2 and Nos3 represent potential targets of therapeutic intervention. The present study enhances understanding of the anti-airway inflammation effects of ICA, especially in asthma.

Advances in research on immunocyte iron metabolism, ferroptosis, and their regulatory roles in autoimmune and autoinflammatory diseases.

Autoimmune diseases commonly affect various systems, but their etiology and pathogenesis remain unclear. Currently, increasing research has highlighted the role of ferroptosis in immune regulation, with immune cells being a crucial component of the body's immune system. This review provides an overview and discusses the relationship between ferroptosis, programmed cell death in immune cells, and autoimmune diseases. Additionally, it summarizes the role of various key targets of ferroptosis, such as GPX4 and TFR, in immune cell immune responses. Furthermore, the release of multiple molecules, including damage-associated molecular patterns (DAMPs), following cell death by ferroptosis, is examined, as these molecules further influence the differentiation and function of immune cells, thereby affecting the occurrence and progression of autoimmune diseases. Moreover, immune cells secrete immune factors or their metabolites, which also impact the occurrence of ferroptosis in target organs and tissues involved in autoimmune diseases. Iron chelators, chloroquine and its derivatives, antioxidants, chloroquine derivatives, and calreticulin have been demonstrated to be effective in animal studies for certain autoimmune diseases, exerting anti-inflammatory and immunomodulatory effects. Finally, a brief summary and future perspectives on the research of autoimmune diseases are provided, aiming to guide disease treatment strategies.

Co-removal and recycling of Ba2+ and Ca2+ in hypersaline wastewater based on the microbially induced carbonate precipitation technique: Overlooked Ba2+ in extracellular and intracellular vaterite.

This study investigates the co-precipitation of calcium and barium ions in hypersaline wastewater under the action of Bacillus licheniformis using microbially induced carbonate precipitation (MICP) technology, as well as the bactericidal properties of the biomineralized product vaterite. The changes in carbonic anhydrase activity, pH, carbonate and bicarbonate concentrations in different biomineralization systems were negatively correlated with variations in metal ion concentrations, while the changes in polysaccharides and protein contents in bacterial extracellular polymers were positively correlated with variations in barium concentrations. In the mixed calcium and barium systems, the harvested minerals were vaterite containing barium. The increasing concentrations of calcium promoted the incorporation and adsorption of barium onto vaterite. The presence of barium significantly increased the contents of O-CO, N-CO, and Ba-O in vaterite. Calcium promoted barium precipitation, but barium inhibited calcium precipitation. After being treated by immobilized bacteria, the concentrations of calcium and barium ions decreased from 400 and 274 to 1.72 and 0 mg/L (GB/T15454-2009 and GB8978-1996). Intracellular minerals were also vaterite containing barium. Extracellular vaterite exhibited bactericidal properties. This research presents a promising technique for simultaneously removing and recycling hazardous heavy metals and calcium in hypersaline wastewater.

LINC00330/CCL2 axis-mediated ESCC TAM reprogramming affects tumor progression.

BACKGROUND: Tumor-associated macrophages (TAMs) significantly influence the progression, metastasis, and recurrence of esophageal squamous cell carcinoma (ESCC). The aberrant expression of long noncoding RNAs (lncRNAs) in ESCC has been established, yet the role of lncRNAs in TAM reprogramming during ESCC progression remains largely unexplored. METHODS: ESCC TAM-related lncRNAs were identified by intersecting differentially expressed lncRNAs with immune-related lncRNAs and performing immune cell infiltration analysis. The expression profile and clinical relevance of LINC00330 were examined using the TCGA database and clinical samples. The LINC00330 overexpression and interference sequences were constructed to evaluate the effect of LINC00330 on ESCC progression. Single-cell sequencing data, CIBERSORTx, and GEPIA were utilized to analyze immune cell infiltration within the ESCC tumor microenvironment and to assess the correlation between LINC00330 and TAM infiltration. ESCC-macrophage coculture experiments were conducted to investigate the influence of LINC00330 on TAM reprogramming and its subsequent effect on ESCC progression. The interaction between LINC00330 and C-C motif ligand 2 (CCL2) was confirmed through transcriptomic sequencing, subcellular localization analysis, RNA pulldown, silver staining, RNA immunoprecipitation, and other experiments. RESULTS: LINC00330 is significantly downregulated in ESCC tissues and strongly associated with poor patient outcomes. Overexpression of LINC00330 inhibits ESCC progression, including proliferation, invasion, epithelial-mesenchymal transition, and tumorigenicity in vivo. LINC00330 promotes TAM reprogramming, and LINC00330-mediated TAM reprogramming inhibits ESCC progression. LINC00330 binds to the CCL2 protein and inhibits the expression of CCL2 and downstream signaling pathways. CCL2 is critical for LINC00330-mediated TAM reprogramming and ESCC progression. CONCLUSIONS: LINC00330 inhibited ESCC progression by disrupting the CCL2/CCR2 axis and its downstream signaling pathways in an autocrine fashion; and by impeding CCL2-mediated TAM reprogramming in a paracrine manner. The new mechanism of TAM reprogramming mediated by the LINC00330/CCL2 axis may provide potential strategies for targeted and immunocombination therapies for patients with ESCC.

Effect of Ba2+ on the biomineralization of Ca2+ and Mg2+ ions induced by Bacillus licheniformis.

The effect of barium ions on the biomineralization of calcium and magnesium ions is often overlooked when utilizing microbial-induced carbonate precipitation technology for removing barium, calcium, and magnesium ions from oilfield wastewater. In this study, Bacillus licheniformis was used to bio-precipitate calcium, magnesium, and barium ions. The effects of barium ions on the physiological and biochemical characteristics of bacteria, as well as the components of extracellular polymers and mineral characteristics, were also studied in systems containing coexisting barium, calcium, and magnesium ions. The results show that the increasing concentrations of barium ions decreased pH, carbonic anhydrase activity, and concentrations of bicarbonate and carbonate ions, while it increased the contents of humic acids, proteins, polysaccharides, and DNA in extracellular polymers in the systems containing all three types of ions. With increasing concentrations of barium ions, the content of magnesium within magnesium-rich calcite and the size of minerals precipitated decreased, while the full width at half maximum of magnesium-rich calcite, the content of O-C=O and N-C=O, and the diversity of protein secondary structures in the minerals increased in systems containing all three coexisting ions. Barium ions does inhibit the precipitation of calcium and magnesium ions, but the immobilized bacteria can mitigate the inhibitory effect. The precipitation ratios of calcium, magnesium, and barium ions reached 81-94%, 68-82%, and 90-97%. This research provides insights into the formation of barium-enriched carbonate minerals and offers improvements for treating oilfield wastewater.

Lanthanide complexes with an azo-dye chromophore ligand: syntheses, crystal structures, and near-infrared luminescence by long-wavelength excitation.

Near-infrared (NIR) emissive probes are becoming increasingly popular in biological sensing and imaging due to the advantages of non-invasiveness and deep tissue-penetrating ability. Herein, a series of complexes of trivalent lanthanide ions (Ln = Yb, Er, and Gd) with the commercially available azo dye chromophore 2R (Na2H2C2R) as ligand and featuring respectively H2O and dimethylsulfoxide (DMSO) as ancillary ligands have been prepared. Formulated as [Ln2(HC2R)2(H2O)10]·8H2O (1-3, Ln = Yb, Er, Gd) and [Ln2(HC2R)2(DMSO)10]·2DMSO (4-6, Ln = Yb, Er, Gd), their structures have been determined by single-crystal X-ray diffraction studies. Photophysical property studies revealed NIR emissions of the DMSO complexes characteristic of Yb(III) and Er(III), effectively sensitized by the dye ligand arising mainly from the π-π* transition of the chromophore. The long-wavelength excitation of the complexes, covering the whole visible-light range and extending into the NIR region, portends the potential applications of such complexes for flexible bioimaging and sensing.

Prognostic utility of blood inflammation biomarkers before and after treatment on the survival of patients with locally advanced non-small cell lung cancer undergoing stereotactic body radiotherapy.

BACKGROUND AND OBJECTIVE: The neutrophil-lymphocyte ratio (NLR) and platelet-lymphocyte ratio (PLR) were significant and succinct indicators of systemic inflammation. We assessed the influence of stereotactic body radiotherapy (SBRT) on NLR and PLR in patients with locally advanced non-small cell lung cancer (LA-NSCLC). METHODS: We reviewed the medical data of patients with LA-NSCLC who underwent SBRT between 1 January 2013 and 31 December 2018. NLR and PLR values recorded at pre- and post-SBRT were examined. We assessed the correlation between pre/post-SBRT NLR and PLR and survival outcomes. The decision tree evaluation was conducted using Chi-square automatic detection. RESULTS: In total, 213 patients were included in the study with a median follow-up duration of 40.00 (ranging from 5.28 to 100.70) months. Upon dichotomization by a median, we identified that post-SBRT NLR > 5.5 and post-SBRT PLR > 382.0 were negatively associated with shorter overall survival (OS). In the multivariate assessment, post-SBRT PLR > 382.0 was the only factor. Based on post-SBRT PLR, tumor locations, and tumor stage, we categorized patients into low, medium, or high-risk groups. CONCLUSIONS: Post-SBRT PLR > 382.0 correlated with survival in patients undergoing SBRT. The decision tree model might play a role in future risk stratification to guide the clinical practice of individualized SBRT for LA-NSCLC.

A Novel NIR Fluorescence Probe with AIE Property to Image Viscosity in Nystatin-Induced Cell Model.

As one of the most significant parameters in cellular microenvironment, viscosity levels could be used to determine the metabolic process of bioactive substances within cells. Abnormal viscosity levels are closely associated with a series of diseases. Therefore, the design and synthesis of fluorescent probes that can monitor changes of intracellular viscosity in real-time is of great significance for the study of disease development process. Here, a new viscosity-recognized NIR fluorescence probe W1 based on quinoline-malonitrile is synthesized, and it is not susceptible to interference substances. Besides, AIE probe W1 shows fast response, excellent photostability, low cytotoxicity, good linear relationship between fluorescence intensity value and viscosity. Based on the above advantages, probe W1 is used to image the change of viscosity level in the cell model induced by nystatin.

Research reviews and prospects of gut microbiota in liver cirrhosis: a bibliometric analysis (2001-2023).

Introduction: The gut-liver axis has emerged as a focal point in chronic liver disorders, prompting more research into the role of the gut microbiota in liver cirrhosis. In individuals with liver cirrhosis, changes in the structure and function of the gut microbiota are closely tied to clinical prognosis. However, there is a scarcity of bibliometric evaluations conducted in this particular field. Methods: This study is aiming to conduct a complete analysis of the knowledge structure and centers pertaining to gut microbiota in liver cirrhosis using bibliometric methods. Publications on gut microbiota and liver cirrhosis from 2001 to 2023 are sourced from the Web of Science Core Collection. For the bibliometric analysis, we employ VOSviewer, CiteSpace, and the R package "bibliometrix". Results: Our study encompasses a comprehensive collection of 3109 articles originating from 96 countries, with notable contributions from leading nations such as the United States and China. The quantity of publications concerning the gut microbiota of liver cirrhosis rises annually. The University of California San Diego, Virginia Commonwealth University, Zhejiang University are the primary research institutions. World Journal of Gastroenterology publishes the most papers in this field, while hepatology is the most frequently co-cited journal. These publications come from a total of 15,965 authors, and the most prolific authors are Bajaj Jasmohan S., Schnabl Bernd and Gillevet Patrick M., while the most co-cited authors are Bajaj Jasmohan S., Younossi Zobair M., and Reiner Wiest. In addition, "dysbiosis", "gut microbiota", "intestinal barrier", "fecal microbiota transplantation", and "complement-system" are the primary keywords of research trends in recent years. Discussion: This study offering a comprehensive insight into the research dynamics surrounding gut microbiota in patients with liver cirrhosis. It delineates the current research frontiers and hotspots, serving as a valuable guide for scholars.

Gut microbiota-dependent modulation of pre-metastatic niches by Jianpi Yangzheng decoction in the prevention of lung metastasis of gastric cancer.

AIM OF THE STUDY: To evaluate the in vitro and in vivo anti-metastasis efficacy of Jianpi Yangzheng (JPYZ) decoction against gastric cancer (GC) and its potential mechanisms. MATERIALS AND METHODS: The distant metastasis of GC cells administered via tail vein injection was assessed using the pre-metastatic niche (PMN) model. 16S rRNA sequencing and GC-MS/MS were applied to determine the component of the gut microbiota and content of short-chain fatty acids (SCFAs) in feces of mice, respectively. The proportion of myeloid-derived suppressor cells (MDSCs) in the lung was evaluated by flow cytometry and immunofluorescence. Serum or tissue levels of inflammation factors including IL-6, IL-10 and TGF-ß were determined by ELISA or Western blot respectively. RESULTS: Injecting GC cells into the tail vein of mice led to the development of lung metastases and also resulted in alterations in the composition of gut microbiota and the levels of SCFAs produced. Nevertheless, JPYZ treatment robustly impeded the effect of GC cells administration. Mechanically, JPYZ treatment not only prevented the alteration in gut microbiota structure, but also restored the SCFAs content induced by GC cells administration. Specifically, JPYZ treatment recovered the relative abundance of genera Moryella, Helicobacter, Lachnoclostridium, Streptococcus, Tuzzerella, GCA-900066575, uncultured_Lachnospiraceae, Rikenellaceae_RC9_gut_group and uncultured_bacterium_Muribaculaceae to near the normal control levels. In addition, JPYZ abrogated MDSCs accumulation in the lung tissue and blocked inflammation factors overproduction in the serum and lung tissues, which subsequently impede the formation of the immunosuppressive microenvironment. Correlation analysis revealed that the prevalence of Rikenellaceae in the model group exhibited a positive correlation with MDSCs proportion and inflammation factor levels. Conversely, the scarcity of Muribaculaceae in the model group showed a negative correlation with these parameters. This suggests that JPYZ might exert an influence on the gut microbiota and their metabolites, such as SCFAs, potentially regulating the formation of the PMN and consequently impacting the outcome of GC metastasis. CONCLUSION: These findings suggest that GC cells facilitate metastasis by altering the gut microbiota composition, affecting the production of SCFAs, and recruiting MDSCs to create a pro-inflammatory pre-metastatic niche. JPYZ decoction counteracts this process by reshaping the gut microbiota structure, enhancing SCFA production, and inhibiting the formation of the pre-metastatic microenvironment, thereby exerting an anti-metastatic effect.

Efficacy and safety of gut microbiota-based therapies in autoimmune and rheumatic diseases: a systematic review and meta-analysis of 80 randomized controlled trials.

BACKGROUND: Previous randomized controlled trials (RCTs) suggested that gut microbiota-based therapies may be effective in treating autoimmune diseases, but a systematic summary is lacking. METHODS: Pubmed, EMbase, Sinomed, and other databases were searched for RCTs related to the treatment of autoimmune diseases with probiotics from inception to June 2022. RevMan 5.4 software was used for meta-analysis after 2 investigators independently screened literature, extracted data, and assessed the risk of bias of included studies. RESULTS: A total of 80 RCTs and 14 types of autoimmune disease [celiac sprue, SLE, and lupus nephritis (LN), RA, juvenile idiopathic arthritis (JIA), spondyloarthritis, psoriasis, fibromyalgia syndrome, MS, systemic sclerosis, type 1 diabetes mellitus (T1DM), oral lichen planus (OLP), Crohn's disease, ulcerative colitis] were included. The results showed that gut microbiota-based therapies may improve the symptoms and/or inflammatory factor of celiac sprue, SLE and LN, JIA, psoriasis, PSS, MS, systemic sclerosis, Crohn's disease, and ulcerative colitis. However, gut microbiota-based therapies may not improve the symptoms and/or inflammatory factor of spondyloarthritis and RA. Gut microbiota-based therapies may relieve the pain of fibromyalgia syndrome, but the effect on fibromyalgia impact questionnaire score is not significant. Gut microbiota-based therapies may improve HbA1c in T1DM, but its effect on total insulin requirement does not seem to be significant. These RCTs showed that probiotics did not increase the incidence of adverse events. CONCLUSIONS: Gut microbiota-based therapies may improve several autoimmune diseases (celiac sprue, SLE and LN, JIA, psoriasis, fibromyalgia syndrome, PSS, MS, T1DM, Crohn's disease, and ulcerative colitis).

Herbal Medicine-Inspired Carbon Quantum Dots with Antibiosis and Hemostasis Effects for Promoting Wound Healing.

Bleeding and bacterial infections are crucial factors affecting wound healing. The usage of herbal medicine-derived materials holds great potential for promoting wound healing. However, the uncertain intrinsic effective ingredients and unclear mechanism of action remain great concerns. Herein, inspired by the herbal medicine Ligusticum wallichii, we reported the synthesis of tetramethylpyrazine-derived carbon quantum dots (TMP-CQDs) for promoting wound healing. Of note, the use of TMP as the precursor instead of L. wallichii ensured the repeatability and homogeneity of the obtained products. Furthermore, TMP-CQDs exhibited high antibacterial activity. Mechanically, TMP-CQDs inhibited the DNA repair, biosynthesis, and quorum sensing of the bacteria and induced intracellular reactive oxygen species (ROS). Moreover, TMP-CQDs could accelerate blood coagulation through activating factor VIII and promoting platelet aggregation. Effective wound healing was achieved by using TMP-CQDs in the Staphylococcus aureus-infected mouse skin wound model. This study sheds light on the development of herbal medicine-inspired materials as effective therapeutic drugs.

[Effect analysis of information-guided enteral nutrition-associated diarrhea treatment process in patients with chronic obstructive pulmonary disease undergoing continuous non-invasive assisted ventilation: a mixed cohort study of pre- and post-control].

OBJECTIVE: To clarify the application effect of information-guided enteral nutrition-associated diarrhea (ENAD) management process in patients with chronic obstructive pulmonary disease (COPD) undergoing non-invasive assisted ventilation. METHODS: A mixed cohort study of pre- and post-control was conducted. Thirty-nine patients with COPD who were admitted to the emergency intensive care unit (ICU) of Huzhou First People's Hospital from July 1, 2021 to July 31, 2022 were enrolled. Taking the completion of the software development of ENAD management software for critically ill patients on January 28, 2022 as the time node, 20 patients admitted from July 1, 2021 to January 28, 2022 were set as the control group, and 19 patients admitted from January 29 to July 31, 2022 were set as the observation group. The two groups of patients received the same enteral nutrition support treatment, and the control group implemented the conventional ENAD treatment process with enteral nutrition intolerance disposal process as the core. On the basis of the control group, the observation group implemented the information-guided ENAD treatment process, and the system software actively captured the information of ENAD patients and reminded the medical team to improve the patient's diarrhea-related examination and provide alternative treatment plans. The duration of antidiarrhea, feeding interruption rate, and energy and protein intake, blood biochemical indexes, incidence of abnormal blood electrolyte metabolism, daily continuous non-invasive assisted ventilation and endotracheal intubation after 7 days of targeted diarrhea intervention were compared between the two groups. RESULTS: Except for the basal pulse rate, there were no significant differences in gender distribution, age, and vital signs, basic nutritional status, arterial blood gas analysis and blood biochemistry at admission between the two groups, indicating comparability between the two groups. When ENAD occurred, the patients in the observation group obtained earlier cessation of diarrhea than those in the control group [days: 3.00 (2.00, 3.25) vs. 4.00 (3.00, 5.00), P < 0.01], and the feeding interruption rate was significantly lower than that in the control group [10.53% (2/19) vs. 65.00% (13/20), P < 0.01]. After 7 days of diarrhea intervention, the energy intake of the observation group was significantly higher than that of the control group [kJ×kg-1×d-1: 66.28 (43.34, 70.36) vs. 47.88 (34.60, 52.32), P < 0.01], the levels of hemoglobin (Hb), albumin (Alb) and serum prealbumin (PAB) were significantly higher than those in the control group [Hb (g/L): 119.79±10.04 vs. 110.20±7.75, Alb (g/L): 36.00 (33.75, 37.25) vs. 31.00 (30.00, 33.00), PAB (mg/L): 155.79±25.78 vs. 140.95±14.97, all P < 0.05], the daily continuous non-invasive assisted ventilation duration was significantly shorter than that of the control group [hours: 14 (12, 16) vs. 16 (14, 18), P < 0.01], and the arterial partial pressure of carbon dioxide (PaCO2) was significantly lower than that of the control group [mmHg (1 mmHg ≈ 0.133 kPa): 66.00 (62.00, 70.00) vs. 68.00 (67.50, 70.05), P < 0.05]. However, there were no significant differences in protein intake, incidence of abnormal electrolyte metabolism, and incidence of endotracheal intubation due to acute respiratory failure between the two groups. CONCLUSIONS: The information-guided ENAD treatment process can enable the COPD patients undergoing continuous non-invasive assisted ventilation who experience ENAD to receive earlier cessation of diarrhea, and improve the protein energy metabolism and respiratory function of the patients.

Immune profiling of pancreatic cancer for radiotherapy with immunotherapy and targeted therapy: Biomarker analysis of a randomized phase 2 trial.

PURPOSE: Immunotherapy alone offered limited survival benefits in pancreatic cancer, while the role of immunotherapy-centric combined therapy remains controversial. Therefore, it is required to develop biomarkers to precisely deliver immunotherapy-based multimodality for pancreatic cancer. METHODS: This is a secondary analysis of an open label, randomized, phase 2 trial, whereas patients with locally recurrent pancreatic cancer after surgery were enrolled. Eligible patients with mutant KRAS and positive immunohistochemical staining of PD-L1 were randomly assigned to receive stereotactic body radiation therapy (SBRT) plus pembrolizumab and trametinib (SBRT + K + M) or SBRT and gemcitabine (SBRT + G). Meanwhile, patients were classified into PD-L1+/tumor infiltrating lymphocytes [TIL(s)]- and PD-L1+/TIL + group for each arm. RESULTS: A total of 170 patients were enrolled and randomly assigned to receive SBRT + K + M (n = 85) or SBRT + G (n = 85). The improved outcomes have been reported in patients with SBRT + K + M in the previous study. In this secondary analysis, the median overall survival (OS) was 17.2 months (95% CI 14.6-19.8 months) in patients with PD-L1+/TIL + and 12.7 months (95% CI 10.8-14.6 months) in patients with PD-L1+/TIL- (HR 0.62, 95% CI 0.39-0.97, p = 0.036) receiving SBRT + K + M. In SBRT + G group, the median OS was 13.1 months (95% CI 10.9-15.3 months) in patients with PD-L1+/TIL- and 12.7 months (95% CI 9.2-16.2 months) in patients with PD-L1+/TIL+ (HR 0.97, 95% CI 0.62-1.52, p = 0.896). Grade 3 or 4 adverse events were found in 16 patients (30.8%) and 10 patients (30.3%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + K + M group respectively; whereas 9 (16.7%) and 8 patients (25.8%) with PD-L1+/TIL- and PD-L1+/TIL + in SBRT + G group. CONCLUSION: PD-L1, TILs and mutant KRAS may be a biomarker to guide clinical practice of radiotherapy and immunotherapy-based regimens in pancreatic cancer if further combined with MEK inhibitors as targeted therapy.

Substituent Positioning Effects on the Magnetic Properties of Sandwich-Type Erbium(III) Complexes with Bis(trimethylsilyl)-Substituted Cyclooctatetraenyl Ligands.

Lanthanide complexes with judiciously designed ligands have been extensively studied for their potential applications as single-molecule magnets. With the influence of ligands on their magnetic properties generally established, recent research has unearthed certain effects inherent to site differentiation due to the different types and varying numbers of substituents on the same ligand platform. Using two new sandwich-type Er(III) complexes with cyclooctatetraenyl (COT) ligands featuring two differently positioned trimethylsilyl (TMS) substituents, namely, [Li(DME)Er(COT1,5-TMS2)2]n (Er1) and [Na(DME)3][Er(COT1,3-TMS2)2] (Er2) [COT1,3-TMS2 and COT1,5-TMS2 donate 1,3- and 1,5-bis(trimethylsilyl)-substituted cyclooctatetraenyl ligands, respectively; DME = 1,2-dimethoxyethane], and with reference to previously reported [Li(DME)3][Er(COT1,4-TMS2)2] (A) and [K(DME)2][Er(COT1,4-TMS2)2] (B), any possible substituent position effects have been explored for the first time. The rearrangement of the TMS substituents from the starting COT1,4-TMS2 to COT1,3-TMS2 and COT1,5-TMS2, by way of formal migration of the TMS group, was thermally induced in the case of Er1, while for the formation of Er2, the use of Na+ in the placement of its Li+ and K+ congeners is essential. Both Er1 and Er2 display single-molecule magnetic behaviors with energy barriers of 170(3) and 172(6) K, respectively. Magnetic hysteresis loops, butterfly-shaped for Er1 and wide open for Er2, were observed up to 12 K for Er1 and 13 K for Er2. Studies of magnetic dynamics reveal the different pathways for relaxation of magnetization below 10 K, mainly by the Raman process for Er1 and by quantum tunneling of magnetization for Er2, leading to the order of magnitude difference in magnetic relaxation times and sharply different magnetic hysteresis loops.

Ultrathin Van der Waals Lanthanum Oxychloride Dielectric for 2D Field-Effect Transistors.

Downsizing silicon-based transistors can result in lower power consumption, faster speeds, and greater computational capacity, although it is accompanied by the appearance of short-channel effects. The integration of high-mobility 2D semiconductor channels with ultrathin high dielectric constant (high-κ) dielectric in transistors is expected to suppress the effect. Nevertheless, the absence of a high-κ dielectric layer featuring an atomically smooth surface devoid of dangling bonds poses a significant obstacle in the advancement of 2D electronics. Here, ultrathin van der Waals (vdW) lanthanum oxychloride (LaOCl) dielectrics are successfully synthesized by precisely controlling the growth kinetics. These dielectrics demonstrate an impressive high-κ value of 10.8 and exhibit a remarkable breakdown field strength (Ebd ) exceeding 10 MV cm-1 . Remarkably, the conventional molybdenum disulfide (MoS2 ) field-effect transistor (FET) featuring a dielectric made of LaOCl showcases an almost negligible hysteresis when compared to FETs employing alternative gate dielectrics. This can be attributed to the flawlessly formed vdW interface and excellent compatibility established between LaOCl and MoS2 . These findings will motivate the further exploration of rare-earth oxychlorides and the development of more-than-Moore nanoelectronic devices.

Efficacy and safety of iguratimod in the treatment of rheumatic and autoimmune diseases: a meta-analysis and systematic review of 84 randomized controlled trials.

Objective: To evaluate efficacy and safety of iguratimod (IGU) in the treatment of rheumatic and autoimmune diseases. Methods: Databases such as Pubmed, Embase, Sinomed were searched (as of July 2022) to collect randomized controlled trials (RCTs) of IGU in the treatment of rheumatic and autoimmune diseases. Two researchers independently screened the literature, extracted data, assessed the risk of bias of the included literature, and performed meta-analysis using RevMan 5.4 software. Results: A total of 84 RCTs and 4 types of rheumatic and autoimmune diseases [rheumatoid arthritis (RA), ankylosing spondylitis (AS), primary Sjögren's syndrome (PSS) and Autoimmune disease with interstitial pneumonia]. Forty-three RCTs reported RA and showed that IGU + MTX therapy can improve ACR20 (RR 1.45 [1.14, 1.84], p = 0.003), ACR50 (RR 1.80 [1.43, 2.26], p < 0.0000), ACR70 (RR 1.84 [1.27, 2.67], p = 0.001), DAS28 (WMD -1.11 [-1.69, -0.52], p = 0.0002), reduce ESR (WMD -11.05 [-14.58, -7.51], p < 0.00001), CRP (SMD -1.52 [-2.02, -1.02], p < 0.00001), RF (SMD -1.65 [-2.48, -0.82], p < 0.0001), and have a lower incidence of adverse events (RR 0.84 [0.78, 0.91], p < 0.00001) than the control group. Nine RCTs reported AS and showed that IGU can decrease the BASDAI score (SMD -1.62 [-2.20, -1.05], p < 0.00001), BASFI score (WMD -1.07 [-1.39, -0.75], p < 0.00001), VAS (WMD -2.01 [-2.83, -1.19], p < 0.00001), inflammation levels (decreasing ESR, CRP and TNF-α). Thirty-two RCTs reported PSS and showed that IGU can reduce the ESSPRI score (IGU + other therapy group: WMD -1.71 [-2.44, -0.98], p < 0.00001; IGU only group: WMD -2.10 [-2.40, -1.81], p < 0.00001) and ESSDAI score (IGU + other therapy group: WMD -1.62 [-2.30, -0.94], p < 0.00001; IGU only group: WMD -1.51 [-1.65, -1.37], p < 0.00001), inhibit the inflammation factors (reduce ESR, CRP and RF) and increase Schirmer's test score (IGU + other therapy group: WMD 2.18 [1.76, 2.59], p < 0.00001; IGU only group: WMD 1.55 [0.35, 2.75], p = 0.01); The incidence of adverse events in IGU group was also lower than that in control group (IGU only group: RR 0.66 [0.48, 0.98], p = 0.01). Three RCTs reported Autoimmune disease with interstitial pneumonia and showed that IGU may improve lung function. Conclusion: Based on current evidence, IGU may be a safe and effective therapy for RA, AS, PSS and autoimmune diseases with interstitial pneumonia. Systematic Review Registration: (CRD42021289489).

Recent Advances in Cyanotoxin Synthesis and Applications: A Comprehensive Review.

Over the past few decades, nearly 300 known cyanotoxins and more than 2000 cyanobacterial secondary metabolites have been reported from the environment. Traditional studies have focused on the toxic cyanotoxins produced by harmful cyanobacteria, which pose a risk to both human beings and wildlife, causing acute and chronic poisoning, resulting in diarrhea, nerve paralysis, and proliferation of cancer cells. Actually, the biotechnological potential of cyanotoxins is underestimated, as increasing studies have demonstrated their roles as valuable products, including allelopathic agents, insecticides and biomedicines. To promote a comprehensive understanding of cyanotoxins, a critical review is in demand. This review aims to discuss the classifications; biosynthetic pathways, especially heterogenous production; and potential applications of cyanotoxins. In detail, we first discuss the representative cyanotoxins and their toxic effects, followed by an exploration of three representative biosynthetic pathways (non-ribosomal peptide synthetases, polyketide synthetases, and their combinations). In particular, advances toward the heterologous biosynthesis of cyanotoxins in vitro and in vivo are summarized and compared. Finally, we indicate the potential applications and solutions to bottlenecks for cyanotoxins. We believe that this review will promote a comprehensive understanding, synthetic biology studies, and potential applications of cyanotoxins in the future.

Facile Preparation of a Novel HfC Aerogel with Low Thermal Conductivity and Excellent Mechanical Properties.

Aerogels emerge as captivating contenders within the realm of high-temperature thermal resistance and thermal insulation. Nevertheless, their practical applications are usually constrained by their inherent brittleness when subjected to rigorous conditions. Herein, employing hafnium dichloride oxide octahydrate (HfOCl2·8H2O) as the hafnium source and resorcinol-formaldehyde (RF) as the carbon precursor, hafnium carbide (HfC) aerogels are fabricated via the sol-gel method complemented with carbothermal reduction reaction. Investigations are conducted into the effects of various molar ratios, duration, and temperatures of calcination on the microstructural features and physico-chemical characteristics of the as-prepared HfC aerogel. The aerogel shows a high BET-specific surface area (601.02 m2/g), which is much larger than those of previously reported aerogels. Furthermore, the HfC aerogel exhibits a low thermal conductivity of 0.053 W/(m·K) and a compressive strength of up to 6.12 MPa after carbothermal reduction at 1500 °C. These excellent thermal insulation and mechanical properties ensure it is ideal for the utilization of high-temperature thermal resistance and thermal insulation in the fields of aerospace.