Thermoresponsive and Substrate Self-Cycling Nanoenzyme System for Efficient Tumor Therapy.

Cerium oxide (CeO2-x) performs well in photothermal and catalytic properties due to its abundance of oxygen vacancies. Based on this, we designed a thermosensitive therapeutic nanoplatform to achieve continuous circular drug release in tumor. It can solve the limitation caused by insufficient substrate in the process of tumor treatment. Briefly, CeO2-x and camptothecin (CPT) were wrapped in an agarose hydrogel, which could be melted by the photothermal effect of CeO2-x. At the same time, the local temperature increase provided photothermal treatment, which could induce the apoptosis of tumor cell. After that, CPT was released to damage the DNA in tumor cells to realize chemical treatment. In addition, CPT could active nicotinamide adenine dinucleotide oxidase to react with O2 to increase the intracellular H2O2. After that, the exposed CeO2-x could catalyze H2O2 to generate cytotoxic reactive oxygen species for chemodynamic therapy. More importantly, CeO2-x could catalyze H2O2 to produce O2, which could combine with the catalytic action of CPT to construct a substrate self-cycling nanoenzyme system. Overall, this self-cycling nanoplatform released hypoxia in the tumor microenvironment and built a multimode tumor treatment, which achieved an ideal antitumor affect.

De novo design of SARS-CoV-2 main protease inhibitors with characteristic binding modes.

The coronavirus disease 2019 (COVID-19) is caused by a novel coronavirus called severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which spreads rapidly all over the world. The main protease (Mpro) is significant to the replication and transcription of viruses, making it an attractive drug target against coronaviruses. Here, we introduce a series of novel inhibitors which are designed de novo through structure-based drug design approach that have great potential to inhibit SARS-CoV-2 Mproin vitro. High-resolution structures show that these inhibitors form covalent bonds with the catalytic cysteine through the novel dibromomethyl ketone (DBMK) as a reactive warhead. At the same time, the designed phenyl group beside the DBMK warhead inserts into the cleft between H41 and C145 through π-π stacking interaction, splitting the catalytic dyad and disrupting proton transfer. This unique binding model provides novel clues for the cysteine protease inhibitor development of SARS-CoV-2 as well as other pathogens.

Epitope mapping and establishment of a blocking ELISA for mAb targeting the p72 protein of African swine fever virus.

The African swine fever virus (ASFV) has the ability to infect pigs and cause a highly contagious acute fever that can result in a mortality rate as high as 100%. Due to the viral epidemic, the pig industry worldwide has suffered significant financial setbacks. The absence of a proven vaccine for ASFV necessitates the development of a sensitive and reliable serological diagnostic method, enabling laboratories to effectively and expeditiously detect ASFV infection. In this study, four strains of monoclonal antibodies (mAbs) against p72, namely, 5A1, 4C4, 8A9, and 5E10, were generated through recombinant expression of p72, the main capsid protein of ASFV, and immunized mice with it. Epitope localization was performed by truncated overlapping polypeptides. The results indicate that 5A1 and 4C4 recognized the amino acid 20-39 aa, 8A9 and 5E10 are recognized at 263-282 aa, which is consistent with the reported 265-280 aa epitopes. Conserved analysis revealed 20-39 aa is a high conservation of the epitopes in the ASFV genotypes. Moreover, a blocking ELISA assay for detection ASFV antibody based on 4C4 monoclonal antibody was developed and assessed. The receiver-operating characteristic (ROC) was performed to identify the best threshold value using 87 negative and 67 positive samples. The established test exhibited an area under the curve (AUC) of 0.9997, with a 95% confidence interval ranging from 99.87 to 100%. Furthermore, the test achieved a diagnostic sensitivity of 100% (with a 95% confidence interval of 95.72 to 100%) and a specificity of 98.51% (with a 95% confidence interval of 92.02 to 99.92%) when the threshold was set at 41.97%. The inter- and intra-batch coefficient of variation were below 10%, demonstrating the exceptional repeatability of the method. This method can detect the positive standard serum at a dilution as high as 1:512. Subsequently, an exceptional blocking ELISA assay was established with high diagnostic sensitivity and specificity, providing a novel tool for detecting ASFV antibodies. KEY POINTS: • Four strains of ASFV monoclonal antibodies against p72 were prepared and their epitopes were identified. • Blocking ELISA method was established based on monoclonal antibody 4C4 with an identified conservative epitope. • The established blocking ELISA method has a good effect on the detection of ASFV antibody.

FAM120A deficiency improves resistance to cisplatin in gastric cancer by promoting ferroptosis.

The occurrence of chemoresistance is an inescapable obstacle affecting the clinical efficacy of cisplatin in gastric cancer (GC). Exploring the regulatory mechanism of cisplatin resistance will help to provide potential effective targets for improving the prognosis of gastric cancer patients. Here, we find that FAM120A is upregulated in GC tissues and higher in cisplatin-resistant GC tissues, and its high expression is positively correlated with the poor outcome of GC patients. Functional studies indicate that FAM120A confers chemoresistance to GC cells by inhibiting ferroptosis. Mechanically, METTL3-induced m6A modification and YTHDC1-induced stability of FAM120A mRNA enhance FAM120A expression. FAM120A inhibits ferroptosis by binding SLC7A11 mRNA and enhancing its stability. FAM120A deficiency enhances cisplatin sensitivity by promoting ferroptosis in vivo. These results reveal the function of FAM120A in chemotherapy tolerance and targeting FAM120A is an effective strategy to alleviate cisplatin resistance in GC.

Supercritical CO2 fluid extract from Stellariae Radix ameliorates 2,4-dinitrochlorobenzene-induced atopic dermatitis by inhibit M1 macrophages polarization via AMPK activation.

Yin chai hu (Radix Stellariae) is a root medicine that is frequently used in Chinese traditional medicine to treat fever and malnutrition. In modern medicine, it has been discovered to have anti-inflammatory, anti-allergic, and anticancer properties. In a previous study, we were able to extract lipids from Stellariae Radix using supercritical CO2 extraction (SRE), and these sterol lipids accounted for up to 88.29% of the extract. However, the impact of SRE on the development of atopic dermatitis (AD) has not yet been investigated. This study investigates the inhibitory effects of SRE on AD development using a 2,4-dinitrochlorobenzene (DNCB)-induced AD mouse model. Treatment with SRE significantly reduced the dermatitis score and histopathological changes compared with the DNCB group. The study found that treatment with SRE resulted in a decrease of pro-inflammatory cytokines TNF-α, CXC-10, IL-12, and IL-1ß in skin lesions. Additionally, immunohistochemical analysis revealed that SRE effectively suppressed M1 macrophage infiltration into the AD lesion. Furthermore, the anti-inflammatory effect of SRE was evaluated in LPS + INF-γ induced bone marrow-derived macrophages (BMDMs) M1 polarization, SRE inhibited the production of TNF-α, CXC-10, IL-12, and IL-1ß and decreased the expression of NLRP3. Additionally, SRE was found to increase p-AMPKT172, but had no effect on total AMPK expression, after administration of the AMPK inhibitor Compound C, the inhibitory effect of SRE on M1 macrophages was partially reversed. The results indicate that SRE has an inhibitory effect on AD, making it a potential therapeutic agent for this atopic disorder.

SETDB1: Progress and prospects in cancer treatment potential and inhibitor research.

SET domain bifurcated methyltransferase 1 (SETDB1) serves as a histone lysine methyltransferase, catalyzing the di- and tri-methylation of histone H3K9. Mounting evidence indicates that the abnormal expression or activity of SETDB1, either through amplification or mutation, plays a crucial role in tumorigenesis and progression. This is particularly evident in the context of tumor immune evasion and resistance to immune checkpoint blockade therapy. Furthermore, there is a robust association between SETDB1 dysregulation and an unfavorable prognosis across various types of tumors. The oncogenic role of SETDB1 primarily arises from its methyltransferase function, which contributes to the establishment of a condensed and transcriptionally inactive heterochromatin state. This results in the inactivation of genes that typically hinder cancer development and silencing of retrotransposons that could potentially trigger an immune response. These findings underscore the substantial potential for SETDB1 as an anti-tumor therapeutic target. Nevertheless, despite significant strides in recent years in tumor biology research, challenges persist in SETDB1-targeted therapy. To better facilitate the development of anti-tumor therapy targeting SETDB1, we have conducted a comprehensive review of SETDB1 in this account. We present the structure and function of SETDB1, its role in various tumors and immune regulation, as well as the advancements made in SETDB1 antagonists. Furthermore, we discuss the challenges encountered and provide perspectives for the development of SETDB1-targeted anti-tumor therapy.

Salmonella enterica serovar Typhimurium remodels mitochondrial dynamics of macrophages via the T3SS effector SipA to promote intracellular proliferation.

Mitochondrial dynamics are critical in cellular energy production, metabolism, apoptosis, and immune responses. Pathogenic bacteria have evolved sophisticated mechanisms to manipulate host cells' mitochondrial functions, facilitating their proliferation and dissemination. Salmonella enterica serovar Typhimurium (S. Tm), an intracellular foodborne pathogen, causes diarrhea and exploits host macrophages for survival and replication. However, S. Tm-associated mitochondrial dynamics during macrophage infection remain poorly understood. In this study, we showed that within macrophages, S. Tm remodeled mitochondrial fragmentation to facilitate intracellular proliferation mediated by Salmonella invasion protein A (SipA), a type III secretion system effector encoded by Salmonella pathogenicity island 1. SipA directly targeted mitochondria via its N-terminal mitochondrial targeting sequence, preventing excessive fragmentation and the associated increase in mitochondrial reactive oxygen species, loss of mitochondrial membrane potential, and release of mitochondrial DNA and cytochrome c into the cytosol. Macrophage replication assays and animal experiments showed that mitochondria and SipA interact to facilitate intracellular replication and pathogenicity of S. Tm. Furthermore, we showed that SipA delayed mitochondrial fragmentation by indirectly inhibiting the recruitment of cytosolic dynamin-related protein 1, which mediates mitochondrial fragmentation. This study revealed a novel mechanism through which S. Tm manipulates host mitochondrial dynamics, providing insights into the molecular interplay that facilitates S. Tm adaptation within host macrophages.

Protist ubiquitin ligase effector PbE3-2 targets cysteine protease RD21A to impede plant immunity.

Clubroot, caused by the soil-borne protist pathogen Plasmodiophora brassicae, is one of the most devastating diseases of Brassica oil and vegetable crops worldwide. Understanding the pathogen infection strategy is crucial for the development of disease control. However, because of its obligate biotrophic nature, the molecular mechanism by which this pathogen promotes infection remains largely unknown. P. brassicae E3 ubiquitin ligase 2 (PbE3-2) is a Really Interesting New Gene (RING)-type E3 ubiquitin ligase in P. brassicae with E3 ligase activity in vitro. Yeast (Saccharomyces cerevisiae) invertase assay and apoplast washing fluid extraction showed that PbE3-2 harbors a functional signal peptide. Overexpression of PbE3-2 in Arabidopsis (Arabidopsis thaliana) resulted in higher susceptibility to P. brassicae and decreases in chitin-triggered reactive oxygen species burst and expression of marker genes in salicylic acid signaling. PbE3-2 interacted with and ubiquitinated host cysteine protease RESPONSIVE TO DEHYDRATION 21A (RD21A) in vitro and in vivo. Mutant plants deficient in RD21A exhibited similar susceptibility and compromised immune responses as in PbE3-2 overexpression plants. We show that PbE3-2, which targets RD21A, is an important virulence factor for P. brassicae. Two other secretory RING-type E3 ubiquitin ligases in P. brassicae performed the same function as PbE3-2 and ubiquitinated RD21A. This study reveals a substantial virulence functional role of protist E3 ubiquitin ligases and demonstrates a mechanism by which protist E3 ubiquitin ligases degrade host immune-associated cysteine proteases to impede host immunity.

[Medical visit status and clinical features in patients with IgG4 related disease].

OBJECTIVE: To understand the medical treatment and clinical characteristics of patients with IgG4-related disease (IgG4-RD) with complex clinical manifestations and easy to be misdiagnosed and missed, and to improve the recognition of this disease among doctors from relevant medical departments. METHODS: A retrospective analysis was conducted on the medical records of patients diagnosed with IgG4-RD who were hospitalized and discharged from Peking University Third Hospital from January 1, 2012 to December 31, 2022. The patient' s medical visit status, clinical manifestations, laboratory examinations, diagnosis, and treatment information were summarized. RESULTS: A total of 116 patients diagnosed with IgG4-RD were included in this study, with a male to female ratio of 2. 52∶ 1 and an average age of (61.83±10.80) years. The departments for initial visits were gastroenterology, general surgery, and ophthalmology. While the departments responsible for definitive diagnosis were gastroenterology, rheumatology and immunology, and respiratory medicine. Twenty-one patients (18. 10%) required consultation and treatment from three or more departments before receiving a definitive diagnosis. The median time from symptom onset to the initial clinic visit was 2 (1, 7) months, and the median time from symptom onset to diagnosis was 1 (1, 12) month. Twenty-four patients (20.69%) underwent surgical resection of the affected sites before diagnosis. According to the classification criteria of IgG4-RD, sixty-eight (58.62%) cases were diagnosed definitively, eight (6.9%) cases were likely to be diagnosed, and 40 (34.48%) cases were suspected to be diagnosed. In the 68 definitively diagnosed patients, the most commonly affected organs were submandibular gland, the pancreas, biliary tract, parotid in sequence. The median serum IgG4 (IgG4, immunoglobulin G4) level was 6.16 (3. 61, 12. 30) g/L. Fifty-seven patients (83.82%) were treated with glucocorticoids, and 14 patients (20.59%) were treated with immunosuppressants. The use of immunosuppressants was mainly in the rheumatology and immunology department (78. 57%). CONCLUSION: IgG4-RD is more common in elderly males, with submandibular gland, the pancreas, biliary tract, and parotid being most commonly affected. The distribution of initial visit departments in patients is wide. The proportion of definitive diagnosis based on pathology is relatively low. In terms of treatment, the main approach is steroid treatment, while the use of immunosuppres-sants is not widespread.

Machine learning classification of polycystic ovary syndrome based on radial pulse wave analysis.

BACKGROUND: Patients with Polycystic ovary syndrome (PCOS) experienced endocrine disorders that may present vascular function changes. This study aimed to classify and predict PCOS by radial pulse wave parameters using machine learning (ML) methods and to provide evidence for objectifying pulse diagnosis in traditional Chinese medicine (TCM). METHODS: A case-control study with 459 subjects divided into a PCOS group and a healthy (non-PCOS) group. The pulse wave parameters were measured and analyzed between the two groups. Seven supervised ML classification models were applied, including K-Nearest Neighbors (KNN), Support Vector Machine (SVM), Decision Trees, Random Forest, Logistic Regression, Voting, and Long Short Term Memory networks (LSTM). Parameters that were significantly different were selected as input features and stratified k-fold cross-validations training was applied to the models. RESULTS: There were 316 subjects in the PCOS group and 143 subjects in the healthy group. Compared to the healthy group, the pulse wave parameters h3/h1 and w/t from both left and right sides were increased while h4, t4, t, As, h4/h1 from both sides and right t1 were decreased in the PCOS group (P < 0.01). Among the ML models evaluated, both the Voting and LSTM with ensemble learning capabilities, demonstrated competitive performance. These models achieved the highest results across all evaluation metrics. Specifically, they both attained a testing accuracy of 72.174% and an F1 score of 0.818, their respective AUC values were 0.715 for the Voting and 0.722 for the LSTM. CONCLUSION: Radial pulse wave signal could identify most PCOS patients accurately (with a good F1 score) and is valuable for early detection and monitoring of PCOS with acceptable overall accuracy. This technique can stimulate the development of individualized PCOS risk assessment using mobile detection technology, furthermore, gives physicians an intuitive understanding of the objective pulse diagnosis of TCM. TRIAL REGISTRATION: Not applicable.

Single-Atom Nanoenzyme-Based Autoluminescence System for Cancer Cell Imaging and Mitochondrial-Targeted Therapy.

The autoluminescence nanoplatform based on a single-atom catalyst has the potential to achieve accurate tumor diagnosis and treatment. Taking advantage of this, glycyrrhetinic acid (GA) and chitosan-modified single Fe-N-C atom catalysts (SAF NPs) loaded with luminol-curcumin (Cur) were fabricated (SAF-LCCG). Once delivered to the tumor, this autoluminescence SAF-LCCG could target the mitochondria to restrain tumor metastasis and promote the production of hydrogen peroxide (H2O2). Then, SAF NPs with Fenton-like properties could actively utilize intracellular H2O2 to produce ·OH for chemodynamic therapy. After that, excess ·OH and H2O2 were transmitted to luminol to emit blue-violet chemiluminescence (CL) for cancer cell imaging. Synchronously, light was transferred to Cur to produce reactive oxygen species (ROS) which realized photodynamic therapy. Besides, Cur could be served as a chemotherapeutic drug to enhance intracellular ROS for penetrating therapy. More importantly, the massive accumulation of ROS in cancer cells can promote the CL intensity of luminol, which realized the cyclic ROS amplification. This autoluminescence nanoplatform was developed for accurate cancer cell imaging, effective inhibition of tumor metastasis, and synergistic and penetrated treatment of tumors.

Escherichia coli-Based In Situ Triggerable Probe as an Amplifier for Sensitive Diagnosis and Penetrated Therapy of Cancer.

Escherichia coli (E. coli) was used for cancer therapy due to the tumor-targeting, catalytic, and surface-reducing properties. Effective diagnosis combined with treatment of cancer based on E. coli, however, was rarely demonstrated. In this study, E. coli was used to surface reduce HAuCl4 and as a carrier to modify riboflavin (Rf) and luminol (E-Au@Rf@Lum). After targeted delivery to tumor, the E-Au@Rf@Lum probe could actively emit 425 nm blue-violet chemiluminescence (CL) to achieve cell imaging for cancer diagnosis. Furthermore, this light could in situ trigger the photosensitizer (Rf) through CL resonance energy transfer, which produces reactive oxygen species (ROS) for accurate photodynamic therapy. In return, the excessive ROS enhanced the blue-violet light which was further absorbed by Rf, and ROS production was cyclically amplified. Abundant ROS broke down the dense extracellular matrix network and penetrated deep into tumors. Besides, E. coli with excellent catalytic property could decompose H2O2 to O2 to relieve tumor hypoxia for a long time and enhance the photosensitized process of Rf. By self-illumination, effective penetration, and tumor hypoxia relief, this work opens a self-amplified therapy modality to tumor.

Low-Dose Staphylococcal Enterotoxin C2 Mutant Maintains Bone Homeostasis via Regulating Crosstalk between Bone Formation and Host T-Cell Effector Immunity.

Studies in recent years have highlighted an elaborate crosstalk between T cells and bone cells, suggesting that T cells may be alternative therapeutic targets for the maintenance of bone homeostasis. Here, it is reported that systemic administration of low-dose staphylococcal enterotoxin C2 (SEC2) 2M-118, a form of mutant superantigen, dramatically alleviates ovariectomy (OVX)-induced bone loss via modulating T cells. Specially, SEC2 2M-118 treatment increases trabecular bone mass significantly via promoting bone formation in OVX mice. These beneficial effects are largely diminished in T-cell-deficient nude mice and can be rescued by T-cell reconstruction. Neutralizing assays determine interferon gamma (IFN-γ) as the key factor that mediates the beneficial effects of SEC2 2M-118 on bone. Mechanistic studies demonstrate that IFN-γ stimulates Janus kinase/signal transducer and activator of transcription (JAK-STAT) signaling, leading to enhanced production of nitric oxide, which further activates p38 mitogen-activated protein kinase (MAPK) and Runt-related transcription factor 2 (Runx2) signaling and promotes osteogenic differentiation. IFN-γ also directly inhibits osteoclast differentiation, but this effect is counteracted by proabsorptive factors tumor necrosis factor alpha (TNF-α) and interleukin 1 beta (IL-1ß) secreted from IFN-γ-stimulated macrophages. Taken together, this work provides clues for developing innovative approaches which target T cells for the prevention and treatment of osteoporosis.

A novel mutation in the TTN gene resulted in left ventricular noncompaction: a case report and literature review.

BACKGROUND: Left ventricular noncompaction (LVNC) is a specific type of cardiomyopathy characterized by coarse trabeculae and interspersed trabecular crypts within the ventricles. Clinical presentation varies widely and may be nonsignificant or may present with progressive heart failure, malignant arrhythmias, and multiorgan embolism. The mode of inheritance is highly heterogeneous but is most commonly autosomal dominant. The TTN gene encodes titin, which is not only an elastic component of muscle contraction but also mediates multiple signalling pathways in striated muscle cells. In recent years, mutations in the TTN gene have been found to be associated with LVNC, but the exact pathogenesis is still not fully clarified. CASE PRESENTATION: In this article, we report a case of an adult LVNC patient with a TTN gene variant, c.87857G > A (p. Trp29286*), that has not been reported previously. This 43-year-old adult male was hospitalized repeatedly for heart failure. Echocardiography showed reduced myocardial contractility, dilated left ventricle with many prominent trabeculae, and a loose texture of the left ventricular layer of myocardium with crypt-like changes. During the out-of-hospital follow-up, the patient had no significant signs or symptoms of discomfort. CONCLUSION: This case report enriches the mutational spectrum of the TTN gene in LVNC and provides a basis for genetic counselling and treatment of this patient. Clinicians should improve their understanding of LVNC, focusing on exploring its pathogenesis and genetic characteristics to provide new directions for future diagnosis and treatment.

Discovery of a novel dual-target inhibitor of CDK12 and PARP1 that induces synthetic lethality for treatment of triple-negative breast cancer.

Triple negative breast cancer (TNBC) is one of the most aggressive breast tumors, with a high rate of recurrence and metastasis as well as a poor prognosis. Consequently, it is urgent to find new targeted therapeutic strategies and development of corresponding drugs. Previous studies have shown that CDK12 inhibitors in combination with PARP1 inhibitors is able to induce synthetic lethality in TNBC cells. Here, we reported simultaneously inhibition of CDK12 and PARP1 by genetic or pharmacological approaches synergistically inhibited the proliferation of TNBC cells. Then, a series of small molecule inhibitors targeting both CDK12 and PARP1 were designed and synthesized. The new dual-target inhibitor (12e) showed potent inhibitory activity against CDK12 (IC50 = 285 nM) and PARP1 (IC50 = 34 nM), as well as good anti-proliferative effects in TNBC cell lines. Meanwhile, compound 12e showed favorable synergistic anti-tumor efficacy in cells and xenografts by inhibiting DNA damage repair, promoting cell cycle arrest and apoptosis. Taken together, we successfully synthesized the first effective CDK12-PARP1 dual inhibitor, which is expected to be an attractive therapeutic strategy for TNBC.

Application of natural polysaccharides and their novel dosage forms in gynecological cancers: therapeutic implications from the diversity potential of natural compounds.

Cancer is one of the most lethal diseases. Globally, the number of cancers is nearly 10 million per year. Gynecological cancers (for instance, ovarian, cervical, and endometrial), relying on hidden diseases, misdiagnoses, and high recurrence rates, have seriously affected women's health. Traditional chemotherapy, hormone therapy, targeted therapy, and immunotherapy effectively improve the prognosis of gynecological cancer patients. However, with the emergence of adverse reactions and drug resistance, leading to the occurrence of complications and poor compliance of patients, we have to focus on the new treatment direction of gynecological cancers. Because of the potential effects of natural drugs in regulating immune function, protecting against oxidative damage, and improving the energy metabolism of the body, natural compounds represented by polysaccharides have also attracted extensive attention in recent years. More and more studies have shown that polysaccharides are effective in the treatment of various tumors and in reducing the burden of metastasis. In this review, we focus on the positive role of natural polysaccharides in the treatment of gynecologic cancer, the molecular mechanisms, and the available evidence, and discuss the potential use of new dosage forms derived from polysaccharides in gynecologic cancer. This study covers the most comprehensive discussion on applying natural polysaccharides and their novel preparations in gynecological cancers. By providing complete and valuable sources of information, we hope to promote more effective treatment solutions for clinical diagnosis and treatment of gynecological cancers.

Laparoscopic parenchyma-sparing resections for solid pseudopapillary tumors located in the head of pancreas.

BACKGROUND: Solid pseudopapillary tumor (SPT) of the pancreas is a rare low-grade malignant tumor. Here, we aimed to determine the safety and feasibility of laparoscopic parenchyma-sparing pancreatectomy for SPT located in the pancreatic head. METHODS: From July 2014 to February 2022, 62 patients with SPT located in the pancreatic head were operated laparoscopically in two institutions. These patients were divided into two groups according to the operative strategy: laparoscopic parenchyma-sparing pancreatectomy (27 patients, group 1) and laparoscopic pancreaticoduodenectomy (35 patients, group 2). The clinical data were retrospectively collected and analyzed in terms of demographic characteristics, perioperative variables, and long-term follow-up outcomes. RESULTS: The demographic characteristics of the patients in the two groups were comparable. Compared to the patients in group 2, those in group 1 required less operative time (263.4 ± 37.2 min vs. 332.7 ± 55.6 min, p < 0.001) and experienced less blood loss (105.1 ± 36.5mL vs. 188.3 ± 150.7 mL, p < 0.001). None of the patients in group 1 had tumor recurrence or metastasis. However, 1 (2.5%) patient in group 2 showed liver metastasis. CONCLUSION: Laparoscopic parenchyma-sparing pancreatectomy is a safe and feasible approach for SPT located in the pancreatic head, with favorable long-term functional and oncological results.

Chitinolyticbacter albus sp. Nov., A Novel Chitin-Degrading Bacterium Isolated from Ancient Wood Rhizosphere Soil.

In this study, a novel aerobic mesophilic bacterial strain with capable of degrading chitin, designated YIM B06366T, was isolated and classified. The rod-shaped, Gram-stain-negative, on-spore-forming bacterium originated from rhizosphere soil sample collected in Kunming City, Yunnan Province, southwest PR China. Strain YIM B06366T exhibited growth at temperatures between 20 and 35 °C (optimum, 30 °C) and at pH 6.0-8.0 (optimum, pH 6.0). The analysis of 16S rRNA gene sequence similarity revealed that strain YIM B06366T was most closely related to type strain Chitinolyticbacter meiyuanensis SYBC-H1T (98.9%). Phylogenetic analysis based on genome data indicated that strain YIM B06366T should be assigned to the genus Chitinolyticbacter. The Average Nucleotide Identity (ANI) and digital DNA-DNA Hybridization (dDDH) values between strain YIM B06366T and the reference strain Chitinolyticbacter meiyuanensis SYBC-H1T were 84.4% and 27.7%, respectively. The major fatty acids included Summed Feature 3 (C16:1 ω6c/C16:1 ω7c), Summed Feature 8 (C18:1 ω6c/C18:1 ω7c), and C16:0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, aminophospholipids, and two unidentified phospholipids. The predominant menaquinone was Q-8, and the genomic DNA G + C content was 64.1%. Considering the polyphasic taxonomic evidence, strain YIM B06366T is proposed as a novel species within the genus Chitinolyticbacter, named Chitinolyticbacter albus sp. nov. (type strain YIM B06366T = KCTC 92434T = CCTCC AB 2022163T).

Histone acetylation gene-based biomarkers as novel markers of the immune microenvironment in glioblastoma.

BACKGROUND: Glioblastoma (GBM) is a primary malignant tumour with high intracranial morbidity, high malignancy and poor prognosis. Abnormal changes in histone acetylation are closely related to the occurrence and development of cancer. However, there is still a lack of systematic research on histone acetylation in GBM. METHODS: Whole-transcriptome sequencing data and clinical data of GBM patients were obtained through the TCGA database. Single-cell RNA-sequencing (scRNA-seq) data from GBM patients were obtained from GSE146711 in the Gene Expression Omnibus database. Cell descending fractionation was first performed for scRNA-seq on GBM. The CellChat and PROGENy scores explore the impact of the histone acetylation pathway in GBM on intercellular chat and tumour pathways. The AddModuleScore function evaluates the enrichment score of histone acetylation in cells and divides them into high-histone acetylation and low-histone acetylation groups. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed on the differential genes between different histone acetylation states, and the biological processes and pathways that may be affected by histone acetylation were evaluated. Based on this, a prognostic model was constructed using least absolute shrinkage and selection operator (LASSO) analysis, and survival analysis was performed to evaluate its prognostic performance. Finally, we also analysed the main effects of the constructed histone acetylation-related model on GBM immune infiltration by multiple methods, and analysed the main mutation data of its different subgroups. RESULTS: GBM samples mainly include seven large cell populations: oligodendrocyte precursor cells (OPCs), myeloid, neoplastic, oligodendrocytes, astrocytes, vascular and neurons. Cellchat and ProgenY scores revealed that in GBM tumours, histone acetylation interacts closely with multiple immune cells and tumour pathways. GO and KEGG analyses revealed the main impact proteins and pathway correlates of histone acetylation. Five histone acetylation genes were screened using LASSO analysis and a prognostic model was constructed. The results revealed that prognostic models were significant in the prognostic stratification of patients in both the training and validation groups of GBM patients. Immune infiltration analysis revealed that the mechanism of histone acetylation in GBM may be related to the immune infiltration of multiple effector immune cells. CONCLUSIONS: Our histone acetylation-based biomarkers are closely associated with immune microenvironmental infiltration and functional mutations in multiple tumour pathways in GBM. This suggests that histone acetylation may reveal microscopic alterations in the tumour microenvironment, and may provide potential evidence and a research basis for the development of novel therapeutic targets for GBM. On this basis, a novel perspective on the spatial biology and immunological understanding of GBM is provided.

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis.

Osteoporosis, a common systematic bone homeostasis disorder related disease, still urgently needs innovative treatment methods. Several natural small molecules were found to be effective therapeutics in osteoporosis. In the present study, quercetin was screened out from a library of natural small molecular compounds by a dual luciferase reporter system. Quercetin was found to upregulate Wnt/ß-catenin while inhibiting NF-κB signaling activities, and thereby rescuing osteoporosis-induced tumor necrosis factor alpha (TNFα) impaired BMSCs osteogenesis. Furthermore, a putative functional lncRNA, Malat1, was shown to be a key mediator in quercetin regulated signaling activities and TNFα-impaired BMSCs osteogenesis, as mentioned above. In an ovariectomy (OVX)-induced osteoporosis mouse model, quercetin administration could significantly rescue OVX-induced bone loss and structure deterioration. Serum levels of Malat1 were also obviously rescued in the OVX model after quercetin treatment. In conclusion, our study demonstrated that quercetin could rescue TNFα-impaired BMSCs osteogenesis in vitro and osteoporosis-induced bone loss in vivo, in a Malat1-dependent manner, suggesting that quercetin may serve as a therapeutic candidate for osteoporosis treatment.