Oncogenic MORC2 in cancer development and beyond.

Microrchidia CW-type zinc finger 2 (MORC2) is a member of the MORC superfamily of nuclear proteins. Growing evidence has shown that MORC2 not only participates in gene transcription and chromatin remodeling but also plays a key in human disease and tumor development by regulating the expression of downstream oncogenes or tumor suppressors. The present review provides an updated overview of MORC2 in the aspect of cancer hallmark and therapeutic resistance and summarizes its upstream regulators and downstream target genes. This systematic review may provide a favorable theoretical basis for emerging players of MORC2 in tumor development and new insight into the potential clinical application of basic science discoveries in the future.

Enhanced hydrophobic interaction between fish (Cyprinus carpio L.) scale gelatin and curcumin: Mechanism study.

To enhance the solubility of hydrophobic nutrients, the hydrophobicity of fish scale gelatin hydrolysate (FSGH) was increased with moderate acid or alkali hydrolysis. Acid-induced FSG hydrolysate (AcFSGH) at 3 h showed a superior curcumin loading efficiency (18.30 ± 0.38 µg/mL) among all FSGHs. Compared with FSG, the proportion of hydrophobic amino acids (from 41.1% to 46.4%) and the hydrophobic interaction (from 12.72 to 20.10 mg/mL) was significantly increased in the AcFSGH. Meanwhile, the transformation of the α-helix (from 12.8% to 4.9%) to the ß-sheet (from 29.0% to 42.8%) was also observed in the AcFSGH. Based on the observation in the molecular weight and morphological analysis, AcFSGH acquired the best hydrophobic interaction with curcumin, presumably due to the formation of the flexible structure of the linear hydrolyzates. The above results call for an investigation of the role of FSG hydrolysate in the synthesis of nanoparticles loaded with bioactive lipophilic compounds.

Network pharmacology and experimental validation on yangjing zhongyu decoction against diminished ovarian reserve.

ETHNOPHARMACOLOGICAL RELEVANCE: Diminished ovarian reserve (DOR) was considered a refractory reproductive endocrine condition that negatively affected female reproductivity. Yangjing Zhongyu Decoction (YJZYD) had effects on treating infertility. However, there were few studies on the mechanisms of YJZYD preserving ovarian reserve. AIM OF THE STUDY: To explore the possible mechanisms of YJZYD against DOR by UPLC-ESI-MS/MS, network pharmacology, and experimental validation. METHODS: The chemicals of YJZYD were measured by UPLC-ESI-MS/MS. The correlating targets of YJZYD and DOR were identified by the ETCM database, GeneCards database, and PubMed database. The common targets were employed with the DAVID database and visualized with the PPI network. GO and KEGG enrichment analyses were carried out to explore biological progression and pathways. In vivo experiments, energy production was assessed by ATP, and apoptosis rate was analyzed by TUNEL. The serum FSH, AMH, and E2 levels were evaluated by ELISA. Western blotting and immunohistochemistry were used to measure the expression of SIRT1, PGC1α, NRF1, COX IV, FSHR, CYP19A1, PI3K, p-Akt, Akt, Bcl-2, and Bax. RESULTS: 132 components in YJZYD were identified by UPLC-ESI-MS/MS. 149 overlapped targets were extracted from YJZYD and DOR, and the top 20 common targets included AKT1 and CYP19A1. ATP binding was involved in GO analysis. In the KEGG enrichment analysis, the metabolic pathway was the top, and the PI3K-Akt signaling pathway was included. In vivo experiments, YJZYD improved ovarian index and histomorphology. After YJZYD treatment, serum FSH, E2, and AMH were well-modulated, and the content of ATP was up-regulated. Besides, the expression of Bax was suppressed in ovarian tissue, while the expressions of SIRT1, PGC1α, NRF1, COX IV, FSHR, CYP19A1, PI3K, Bcl-2, and p-Akt/Akt were enhanced. CONCLUSION: YJZYD could attenuate reproductive endocrine disturbance and ovarian lesions in vivo by mediating steroidogenesis, energy metabolism, and cell apoptosis. This study uncovered the mechanisms of YJZYD against DOR, providing a theoretical basis for further study.

Review of traditional uses, phytochemistry and pharmacology of Tibetan Medicine tangchong.

ETHNOPHARMACOLOGICAL RELEVANCE: Tangchong (ཐང་ཕྲོམ།), a term in the Tibetan language, encompasses a diverse group of plants belonging to different genera of the Solanaceae family. These plants have been utilized in traditional Tibetan medicine for centuries and are currently still employed to treat a variety of ailments, including acute and severe abdominal pain, intestinal obstruction, epilepsy, ascariasis, lung abscess, and other diseases. The therapeutic properties of tangchong are attributed to the presence of tropane alkaloids (TAs), although recent research has also revealed their toxicity. AIM OF THIS REVIEW: The purpose of this review is to provide a comprehensive analysis of the traditional uses of tangchong, as well as the phytochemical and pharmacological studies conducted on this plant. The review aims to offer a critical update on the current state of knowledge of tangchong and to identify new opportunities for exploring its therapeutic potential. MATERIALS AND METHODS: To gather information on tangchong, we conducted a thorough search of several scientific databases, including Google Scholar, Web of Science, Scifinder, Baidu Scholar, PubMed, and CNKI. RESULTS: This review summarizes the traditional usage of 11 plants, 168 chemical components, including alkaloids, flavonoids, steroids, amides, coumarins, etc., describes the pharmacological activities of these medicinal plants and their mechanisms of action, provides an elaboration of toxicology, and provides new plant-derived drugs and herbal preparations from tangchong. CONCLUSIONS: Clarity regarding the source of the drug is crucial to ensure the safety and efficacy of clinical applications of Tibetan medicine. In this paper, we provide a comprehensive review of tangchong, including its traditional medicinal uses, chemical composition, pharmacology, toxicology, and quality control measures. Our analysis highlights the significant value of tangchong as an ethnomedicinal resource, with pharmacological activities primarily linked to its alkaloid content. Furthermore, this review serves as a valuable reference for future research on alkaloid-containing ethnomedicines.

The efficacy of sodium bicarbonated Ringer's solution versus lactated Ringer's solution in elderly patients undergoing gastrointestinal surgery: a prospective randomized controlled trial.

OBJECTIVE: To investigate the effect of sodium bicarbonated Ringer's solution (BRS) on lactate metabolism, acid-base balance, and clinical outcomes in elderly patients undergoing gastrointestinal surgery. METHODS: A total of 60 elderly patients undergoing gastrointestinal surgery were enrolled in this prospective, randomized controlled study. The participants were randomly assigned to the BRS group (n = 30) or sodium lactated Ringer's solution (LRS) group (n = 30) where they received goal-directed fluid therapy with BRS or LRS, respectively. The primary outcome was the incidence of postoperative hyperlactatemia, whereas the secondary outcomes included pH, bicarbonate, base excess (BE), liver function, and postoperative complications within 30 days. Linear regression was conducted to screen the factors affecting lactate concentration. RESULTS: After fluid therapy, the probability of hyperlactatemia was lower in the BRS group than in the LRS group (3.3% vs. 40.0%, P < 0.001). No significant difference in bicarbonate, pH, and BE was observed between the groups (P > 0.05). Furthermore, the incidence of major complications and the length of hospital stay were not significantly different (P > 0.05). However, the BRS group had a lower risk of minor complications than the LRS group (50.0% vs. 76.7%, P = 0.032), particularly in terms of impaired liver function (16.7% vs. 43.3%, P = 0.024). Diabetes, hypotension, and volume of LRS infused were highly correlated with lactate concentration. CONCLUSION: BRS is more beneficial to the reduction of the incidence of postoperative hyperlactatemia and the risk of minor postoperative complications in elderly patients undergoing gastrointestinal surgery. Therefore, BRS may be a better option for perioperative fluid therapy in elderly patients undergoing gastrointestinal surgery.

Basic research and clinical exploration of cold atmospheric plasma for skin wounds.

Skin wounds, such as burns, diabetic foot ulcers, pressure sores, and wounds formed after laser or surgical treatment, comprise a very high proportion of dermatological disorders. Wounds are treated in a variety of ways; however, some wounds are greatly resistant, resulting in delayed healing and an urgent need to introduce new alternatives. Our previous studies have shown that cold atmospheric plasma (CAP) has antibacterial activity and promotes cell proliferation, differentiation, and migration in vitro. To further advance the role of CAP in wound healing, we evaluated the safety and efficacy of CAP in vitro by irradiation of common refractory bacteria on the skin, irradiation of normal skin of rats and observing reactions, treatment of scald wounds in rats, and treating clinically common acute wounds. Our findings revealed that CAP can eliminate refractory skin bacteria in vitro; CAP positively affected wound healing in a rat scalding wound model; and direct CAP irradiation of low intensity and short duration did not lead to skin erythema or edema. CAP promises to be a new, economical, and safe means of wound treatment.

[Application characteristics and modern research progress of "bone-approaching" acupuncture].

The paper explores the evolution of "bone-approaching" acupuncture, its effect target and mechanism. The concrete operation procedure of "bone-approaching" method is recorded originally in Huangdi Neijing (Inner Canon of Yellow Emperor) as short needling and Shu needling (referring to the category of the five needling technique). The periosteum is the most effective stimulation target of "bone-approaching" acupuncture for analgesia, regaining consciousness and regulating spirit. The "bone-approaching" acupuncture is not only prominently effective on bone bi syndrome, but also has the unique effect on painful, encephalogenic and emotional diseases. The paper summarizes and improves "bone-approaching" acupuncture, i.e. "touching bone surface" with needle tip by slow insertion, "touching bone surface" without pain by swift insertion and "touching bone" with needle body by oblique insertion. It contributes to the inheritance, development and supplementation to the bone needling techniques in Huangdi Neijing and is significant for broadening the clinical application range of acupuncture.

Insights into the Mechanisms and Structure of Breakage-Fusion-Bridge Cycles in Cervical Cancer using Long-Read Sequencing.

Cervical cancer is caused by human papillomavirus (HPV) infection, has few approved targeted therapeutics, and is the most common cause of cancer death in low-resource countries. We characterized 19 cervical and four head and neck cell lines using long-read DNA and RNA sequencing and identified the HPV types, HPV integration sites, chromosomal alterations, and cancer driver mutations. Structural variation analysis revealed telomeric deletions associated with DNA inversions resulting from breakage-fusion-bridge (BFB) cycles. BFB is a common mechanism of chromosomal alterations in cancer, and this is one of the first analyses of these events using long-read sequencing. Analysis of the inversion sites revealed staggered ends consistent with exonuclease digestion of the DNA after breakage. Some BFB events are complex, involving inter- or intra-chromosomal insertions or rearrangements. None of the BFB breakpoints had telomere sequences added to resolve the dicentric chromosomes and only one BFB breakpoint showed chromothripsis. Five cell lines have a Chr11q BFB event, with YAP1/BIRC2/BIRC3 gene amplification. Indeed, YAP1 amplification is associated with a 10-year earlier age of diagnosis of cervical cancer and is three times more common in African American women. This suggests that cervical cancer patients with YAP1 / BIRC2 / BIRC3 -amplification, especially those of African American ancestry, might benefit from targeted therapy. In summary, we uncovered new insights into the mechanisms and consequences of BFB cycles in cervical cancer using long-read sequencing.

Silicon composition and stoichiometric ratios with other nutrients in the lower Minjiang River, Southeast China.

Over the past decades, rivers have delivered imbalanced nutrient loads to coastal marine ecosystems due to human activities, which leads to serious regional or global eutrophication problems. The Minjiang River is heavily influenced by human activities. To understand the changing characteristics of nutrient transport ratios in the Minjiang River waters, we measured the seasonal variations of carbon, nitrogen, phosphorus and silicon nutrients in the lower surface waters of the Minjiang River between July 2019 and July 2020. The results showed that the annual average contents of dissolved silicon (DSi), lithogenic silicon (LSi) and biogenic silicon (BSi) in the surface waters of the lower Minjiang River were 5.30, 4.58 and 2.37 mg·L-1, respectively. There were large seasonal differences among these parameters, with higher content of DSi than LSi and BSi in summer, higher content of DSi than BSi and LSi in autumn and higher content of LSi than DSi and BSi in winter. The proportions of DSi in total silicon tended to decrease gradually from land to sea, while the proportion of BSi was on the contrary. In term of stoichiometric ratios, the Minjiang River mostly presented carbon or phosphorus limitation and was unlimited by silicon or nitrogen. About 1.03×1010 mol DSi and 0.46 ×1010 mol BSi were delivered via the Minjiang River to the ocean yearly, showing a decreasing trend year by year. Based on the data in recent years, the nutrient loads of carbon, nitrogen, and phosphorus transported by Minjiang River showed an increasing trend. The imbalanced nutrient loads may lead to changes in the structure and function of the river, estuary, and offshore ecosystems. The study of nutrient stoichiometric ratios can provide a theoretical basis for solving the problems in structural balance of nutrients and eutrophication in Minjiang River estuary and adjacent marine waters.

The toxic mechanism of tetracycline on root tips in hulless barley (Hordeum vulgare L. var. nudum).

Tetracycline (TC) is a commonly used antibiotic that affects various physiological processes in plants. However, its negative effects on plants remain poorly understood at the molecular level. To ascertain the TC toxicity in the roots, transcriptomic, cytological, and physiological analyses were performed to explore the molecular mechanisms of TC influencing the growth of hulless barley root. At a low concentration (1 mg/L), TC promoted root growth by upregulating the genes related to the flavonoid pathway. At high concentrations (10, 100, and 200 mg/L), TC downregulated genes related to homologous recombination in the root meristem zone and inhibited the mitosis index by 16.4%. Disruption of the DNA repair process can lead to chromosomal aberrations, resulting in a 6.8% C-mitosis rate in the most severe cases. Finally, root growth was inhibited by TC, as evidenced by a reduction in root viability, an increase in reactive oxygen species content, and an inhibition of root length. Cross-comparison of physiological and cytological characterizations and transcriptomic information revealed changes in genetic processes under TC stress. Overall, we present an early genetic strategy to study the significant influence of TC stress on roots.

Nanofiber Composite Microchannel-Containing Injectable Hydrogels for Cartilage Tissue Regeneration.

Articular cartilage tissue is incapable of self-repair and therapies for cartilage defects are still lacking. Injectable hydrogels have drawn much attention in the field of cartilage regeneration. Herein, the novel design of nanofiber composite microchannel-containing hydrogels inspired by the tunnel-piled structure of subway tunnels is proposed. Based on the aldehydized polyethylene glycol/carboxymethyl chitosan (APA/CMCS) hydrogels, thermosensitive gelatin microrods (GMs) are used as a pore-forming agent, and coaxial electrospinning polylactic acid/gelatin fibers (PGFs) loaded with kartogenin (KGN) are used as a reinforcing agent and a drug delivery system to construct the nanofiber composite microchannel-containing injectable hydrogels (APA/CMCS/KGN@PGF/GM hydrogels). The in situ formation, micromorphology and porosity, swelling and degradation, mechanical properties, self-healing behavior, as well as drug release of the nanofiber composite microchannel-containing hydrogels are investigated. The hydrogel exhibits good self-healing ability, and the introduction of PGF nanofibers can significantly improve the mechanical properties. The drug delivery system can realize sustained release of KGN to match the process of cartilage repair. The microchannel structure effectively promotes bone marrow mesenchymal stem cell (BMSC) proliferation and ingrowth within the hydrogels. In vitro and animal experiments indicate that the APA/CMCS/KGN@PGF/GM hydrogels can enhance the chondrogenesis of BMSCs and promote neocartilage formation in the rabbit cartilage defect model.

Coinfection of SARS-CoV-2 and influenza A (H3N2) detected in bronchoalveolar lavage fluid of a patient with long COVID using metagenomic next-generation sequencing: a case report.

The growing number of long COVID cases has drawn clinical attention to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which has been spreading worldwide since winter 2019. Its symptoms are not limited to fatigue and shortness of breath but also affect daily life. We report the use of metagenomic next-generation sequencing (mNGS) to detect coinfection with SARS-CoV-2 and influenza A virus in a patient with long COVID. The patient was admitted with fever, expectoration, fatigue, and shortness of breath. The PCR test was negative due to possible clearance of SARS-Cov-2 in the upper respiratory tract of patients with long COVID. Other routine microbiological tests were also negative, making the clinical diagnosis difficult. Bronchoalveolar lavage fluid (BALF) samples were tested using mNGS. The patient was diagnosed and treated promptly, recovered quickly, and continued taking azvudine after discharge; his condition was stable. This study illustrates that mNGS may be valuable for the timely diagnosis of patients with long COVID and their mixed infections.

Virome of high-altitude canine digestive tract and genetic characterization of novel viruses potentially threatening human health.

The majority of currently emerging infectious illnesses are zoonotic infections, which have caused serious public health and economic implications. The development of viral metagenomics has helped us to explore unknown viruses. We collected 1,970 canine feces from Yushu and Guoluo in the plateau region of China for this study to do a metagenomics analysis of the viral community of the canine digestive tract. Our analysis identified 203 novel viruses, classified into 11 known families and 2 unclassified groups. These viruses include the hepatitis E virus, first identified in dogs, and the astrovirus, coronavirus, polyomavirus, and others. The relationship between the newly identified canine viruses and known viruses was investigated through the use of phylogenetic analysis. Furthermore, we demonstrated the cross-species transmission of viruses and predicted new viruses that may cause diseases in both humans and animals, providing technical support for the prevention and control of diseases caused by environmental pollution viruses. IMPORTANCE Most emerging infectious diseases are due to zoonotic disease agents. Because of their effects on the security of human or animal life, agriculture production, and food safety, zoonotic illnesses and livestock diseases are of worldwide significance. Because dogs are closely related to humans and domestic animals, they serve as one of the important links in the transmission of zoonotic and livestock diseases. Canines can contaminate the environment in which humans live such as water and soil through secretions, potentially altering the human gut microbiota or causing diseases. Our study enriched the viral community in the digestive tract microbiome of dogs and found types of viruses that threaten human health, providing technical support for the prevention and control of early warning of diseases caused by environmental contaminant viruses.

Screening of Potential Probiotic Lactobacillaceae and Their Improvement of Type 2 Diabetes Mellitus by Promoting PI3K/AKT Signaling Pathway in db/db Mice.

The study aimed to isolate Lactobacillaceae strains with in vitro hypoglycemic activity and probiotic properties and to determine their antidiabetic abilities in vivo. Lactiplantibacillus plantarum 22, L. plantarum 25, Limosilactobacillus fermentum 11, and L. fermentum 305 with high in vitro hypoglycemic activity were screened from 23 strains of Lactobacillaceae isolated from human feces and identified by 16S rDNA sequencing. The fasting blood glucose (FBG) of the mice was recorded weekly. After 12 weeks, liver, kidney, and pancreas tissues were stained with hematoxylin and eosin (H&E) to observe histomorphology; the inflammatory factors were assayed by Quantitative Real-time PCR; PI3K and AKT were measured by Western blot; the short-chain fatty acids (SCFAs) were determined by LC-MS/MS. Inhibitory activities of L. plantarum 22, L. plantarum 25, L. fermentum 11, and L. fermentum 305 against α-amylase were 62.29 ± 0.44%, 51.81 ± 3.65%, 58.40 ± 1.68%, and 57.48 ± 5.04%, respectively. Their inhibitory activities to α-glucosidase were 14.89 ± 0.38%, 15.32 ± 0.89%, 52.63 ± 3.07%, and 51.79 ± 1.13%, respectively. Their survival rate after simulated gastrointestinal test were 12.42 ± 2.84%, 9.10 ± 1.12%, 5.86 ± 0.52%, and 8.82 ± 2.50% and their adhesion rates to Caco-2 cell were 6.09 ± 0.39%, 6.37 ± 0.28%, 6.94 ± 0.27%, and 6.91 ± 0.11%, respectively. The orthogonal tests of bacterial powders of the four strains showed that the maximum inhibitory activities to α-amylase and α-glucosidase were 93.18 ± 1.19% and 75.33 ± 2.89%, respectively. The results showed that the mixture of Lactobacillaceae could lower FBG, reduce inflammation, and liver, kidney, and pancreas damage, promote PI3K/AKT signaling pathway, and increase the content of SCFAs. The combination of L. plantarum 22, L. plantarum 25, L. fermentum 11, and L. fermentum 305 can potentially improve type 2 diabetes mellitus (T2DM).

Ginsenoside RG1-induced mesenchymal stem cells alleviate diabetic cardiomyopathy through secreting exosomal circNOTCH1 to promote macrophage M2 polarization.

Diabetic cardiomyopathy (DCM) is a cardiac complication resulting from long-term uncontrolled diabetes, characterized by myocardial fibrosis and abnormal cardiac function. This study aimed at investigating the potential of ginsenoside RG1 (RG1)-induced mesenchymal stem cells (MSCs) in alleviating DCM. A DCM mouse model was constructed, and the effects of RG1-induced MSCs on myocardial function and fibrosis in diabetic mice were evaluated. RG1-induced MSCs were cocultured with high glucose-treated fibroblasts for subsequent functional and mechanism assays. It was discovered that RG1-induced MSCs secrete exosomes that induce macrophage M2 polarization. Mechanistically, exosomes derived from RG1-induced MSCs transferred circNOTCH1 into macrophages, activating the NOTCH signaling pathway. A competing endogenous RNA (ceRNA) regulatory axis consisting of circNOTCH1, miR-495-3p, and NOTCH1 was found to contribute to DCM alleviation.. This study unveiled that exosomal circNOTCH1 secreted by RG1-induced MSCs can alleviate DCM by activating the NOTCH signaling pathway to induce macrophage M2 polarization. This finding may contribute to the development of new therapeutic approaches for DCM.

The Synergism of Human Lactobacillaceae and Inulin Decrease Hyperglycemia via Regulating the Composition of Gut Microbiota and Metabolic Profiles in db/db Mice.

This study aimed to evaluate the effects of Limosilactobacillus fermentum and Lactiplantibacillus plantarum isolated from human feces coordinating with inulin on the composition of gut microbiota and metabolic profiles in db/db mice. These supplements were administered to db/db mice for 12 weeks. The results showed that the Lactobacillaceae coordinating with inulin group (LI) exhibited lower fasting blood glucose levels than the model control group (MC). Additionally, LI was found to enhance colon tissue and increase the levels of short-chain fatty acids. 16S rRNA sequencing revealed that the abundance of Corynebacterium and Proteus, which were significantly increased diabetes. in the MC group compared with NC group, were significantly decreased by the treatment of LI that also restored the key genera of the Lachnospiraceae_NK4A136_group, Lachnoclostridium, Ruminococcus_gnavus_group,Desulfovibrio, and Lachnospiraceae_UCG-006. Untargeted metabolomics analysis showed thatlotaustralin, 5-hydroxyindoleacetic acid, and 13(S)-HpODE were increased while L-phenylalanine, and L-tryptophan were decreased in the MC group compared with the NC group. However, the intervention of LI reversed the levels of these metabolites in the intestine. Correlation analysis revealed that Lachnoclostridium and Ruminococcus_gnavus_group were negatively correlated with 5-hydroxyindoleacetic acid and 13 (S)-HpODE, but positively correlated with L-tryptophan. 13(S)-HpODE was involved in the "linoleic acid metabolism". L-tryptophan and 5-hydroxyindoleacetic acid were involved in "tryptophan metabolism" and "serotonergic synapse". These findings suggest that LI may alleviate type 2 diabetes symptoms by modulating the abundance of Ruminococcus_gnavus_group and Lachnoclostridium to regulate the pathways of "linoleic acid metabolism", "serotonergic synapse", and" tryptophan metabolism". Our results provide new insights into prevention and treatment of type 2 diabetes.

Delta-radiomics features for predicting the major pathological response to neoadjuvant chemoimmunotherapy in non-small cell lung cancer.

OBJECTIVES: To investigate if delta-radiomics features have the potential to predict the major pathological response (MPR) to neoadjuvant chemoimmunotherapy in non-small cell lung cancer (NSCLC) patients. METHODS: Two hundred six stage IIA-IIIB NSCLC patients from three institutions (Database1 = 164; Database2 = 21; Database3 = 21) who received neoadjuvant chemoimmunotherapy and surgery were included. Patients in Database1 were randomly assigned to the training dataset and test dataset, with a ratio of 0.7:0.3. Patients in Database2 and Database3 were used as two independent external validation datasets. Contrast-enhanced CT scans were obtained at baseline and before surgery. The delta-radiomics features were defined as the relative net change of radiomics features between baseline and preoperative. The delta-radiomics model and pre-treatment radiomics model were established. The performance of Immune-Related Response Evaluation Criteria in Solid Tumors (iRECIST) for predicting MPR was also evaluated. RESULTS: Half of the patients (106/206, 51.5%) showed MPR after neoadjuvant chemoimmunotherapy. For predicting MPR, the delta-radiomics model achieved a satisfying area under the curves (AUCs) values of 0.768, 0.732, 0.833, and 0.716 in the training, test, and two external validation databases, respectively, which showed a superior predictive performance than the pre-treatment radiomics model (0.644, 0.616, 0.475, and 0.608). Compared with iRECIST criteria (0.624, 0.572, 0.650, and 0.466), a mixed model that combines delta-radiomics features and iRECIST had higher AUC values for MPR prediction of 0.777, 0.761, 0.850, and 0.670 in four sets. CONCLUSION: The delta-radiomics model demonstrated superior diagnostic performance compared to pre-treatment radiomics model and iRECIST criteria in predicting MPR preoperatively in neoadjuvant chemoimmunotherapy for stage II-III NSCLC. CLINICAL RELEVANCE STATEMENT: Delta-radiomics features based on the relative net change of radiomics features between baseline and preoperative CT scans serve a vital support tool in accurately identifying responses to neoadjuvant chemoimmunotherapy, which can help physicians make more appropriate treatment decisions. KEY POINTS: • The performances of pre-treatment radiomics model and iRECIST model in predicting major pathological response of neoadjuvant chemoimmunotherapy were unsatisfactory. • The delta-radiomics features based on relative net change of radiomics features between baseline and preoperative CT scans may be used as a noninvasive biomarker for predicting major pathological response of neoadjuvant chemoimmunotherapy. • Combining delta-radiomics features and iRECIST can further improve the predictive performance of responses to neoadjuvant chemoimmunotherapy.

Integrative analysis of an endoplasmic reticulum stress-related signature in multiple myeloma.

BACKGROUND: Multiple myeloma (MM) is a malignancy in which plasma cells proliferate abnormally, and it remains incurable. The cells are characterized by high levels of endoplasmic reticulum stress (ERS) and depend on the ERS response for survival. Thus, we aim to find an ERS-related signature of MM and assess its diagnostic value. METHODS: We downloaded three datasets of MM from the Gene Expression Omnibus database. After identifying ERS-related differentially expressed genes (ERDEGs), we analyzed them using Gene Ontology enrichment analysis. A protein-protein interaction network, a transcription factor-mRNA network, a miRNA-mRNA network and a drug-mRNA network were constructed to explore the ERDEGs. The clinical application of these genes was identified by calculating the infiltration of immune cells and using receiver operating characteistic analyses. Finally, qPCR was performed to further confirm the roles of ERDEGs. RESULTS: We obtained nine ERDEGs of MM. Gene Ontology enrichment indicated that the ERDEGs played a role in the endoplasmic reticulum membrane. Additionally, the protein-protein interaction network showed interaction among the ERDEGs, and there were 20 proteins, 107 transcription factors, 42 drugs or molecular compounds and 51 miRNAs which were likely to interact with the nine genes. In addition, immune cell infiltration analyses showed that there was a strong correlation between the nine genes and immune cells, and these potential biomarkers exhibited good diagnostic values. Finally, the expression of ERDEGs in MM cells was different from that in healthy donor samples. CONCLUSION: The nine ERS-related genes, CR2, DHCR7, DNAJC3, KDELR2, LPL, OSBPL3, PINK1, VCAM1 and XBP1 are potential biomarkers of MM, and this supports further clinical development of the diagnosis and treatment of MM.

A new benzophenone derivative from Aspergillus fumigatus WJ-131.

A new benzophenone derivative, 8'-hydroxymonomethylsulochrin (1), together with eighteen known compounds (2-19) were produced by the endophytic fungus Aspergillus fumigatus WJ-131, isolated from the stem of Gardenia jasminoides. The structure of 1 was determined by extensive spectroscopic analysis and X-ray crystallography. Under the condition of concentration of 20.0 µM, the splenic lymphocytes proliferation rates of compounds 1 and 7 induced by LPS were 39.4% and 38.1% (LPS, the splenic lymphocytes cell proliferation rates of 21.3%), and the splenic lymphocytes proliferation rate of compounds 7 induced by ConA is 44.6% (ConA, the splenic lymphocytes proliferation rates of 28.9%). Therefore, compounds 1 and 7 promoted the proliferation of ConA/LPS-stimulated splenic lymphocytes at 20.0 µM in vitro. In addition, compound 1 showed weak antibacterial activity against Fusarium oxysporum.