Comparative Genomics Unveils Functional Diversity, Pangenome Openness, and Underlying Biological Drivers among Bacillus subtilis Group.

The Bacillus subtilis group (Bs group), with Bacillus subtilis as its core species, holds significant research and economic value in various fields, including science, industrial production, food, and pharmaceuticals. However, most studies have been confined to comparative genomics analyses and exploration within individual genomes at the level of species, with few conducted within groups across different species. This study focused on Bacillus subtilis, the model of Gram-positive bacteria, and 14 other species with significant research value, employing comparative pangenomics as well as population enrichment analysis to ascertain the functional enrichment and diversity. Through the quantification of pangenome openness, this work revealed the underlying biological drivers and significant correlation between pangenome openness and various factors, including the distribution of toxin-antitoxin- and integrase-related genes, as well as the number of endonucleases, recombinases, repair system-related genes, prophages, integrases, and transfer mobile elements. Furthermore, the functional enrichment results indicated the potential for secondary metabolite, probiotic, and antibiotic exploration in Bacillus licheniformis, Bacillus paralicheniformis, and Bacillus spizizenii, respectively. In general, this work systematically exposed the quantification of pangenome openness, biological drivers, the pivotal role of genomic instability factors, and mobile elements, providing targeted exploration guidance for the Bs group.

Natural down fiber-reinforced and polypyrrole-modified silk fibroin composite aerogel for efficient solar steam generation toward seawater desalination and wastewater treatment.

Poor mechanical properties and low photothermal efficiency of silk fibroin (SF)-based aerogels are current challenges that need to be addressed. Herein, SF composite aerogel was developed to enhance the mechanical properties through physical interpenetration of natural down fiber (Df) and hydrogen bonds formed among SF, Df, and polypyrrole (PPy) and to improve the evaporation performance via in-situ polymerization of PPy. The resultant Df/PPy@SF aerogel showed significant improvement of compressive stress (194.29 kPa), which was 6.96 times than that of SF aerogel (27.91 kPa), and also good compression resiliency. Furthermore, due to uniform distribution of PPy and high porosity of 95.27 %, Df/PPy@SF aerogel possessed high light absorbance of 99.87 % and low thermal conductivity (0.043 W·m-1·K-1). Thus, the Df/PPy@SF aerogel evaporator demonstrated high evaporation rates of 2.12 kg·m-2·h-1 for 3.5 wt% saline water, 2.04-2.15 kg·m-2·h-1 for various dye water, and 2.10 kg·m-2·h-1 for actual dye wastewater. Moreover, the developed aerogel exhibited evaporation stability and outstanding salt-resistance when treating seawater due to continuous water supply by superhydrophilic porous aerogel. Therefore, these findings demonstrate the excellent performance of Df/PPy@SF aerogel and will inspire further research on developing natural fiber-reinforced aerogels for use in the fields of solar water evaporation, energy, and other related applications.

Research Progress of Aging-related MicroRNAs.

Senescence refers to the irreversible state in which cells enter cell cycle arrest due to internal or external stimuli. The accumulation of senescent cells can lead to many age-related diseases, such as neurodegenerative diseases, cardiovascular diseases, and cancers. MicroRNAs are short non-coding RNAs that bind to target mRNA to regulate gene expression after transcription and play an important regulatory role in the aging process. From nematodes to humans, a variety of miRNAs have been confirmed to alter and affect the aging process. Studying the regulatory mechanisms of miRNAs in aging can further deepen our understanding of cell and body aging and provide a new perspective for the diagnosis and treatment of aging-related diseases. In this review, we illustrate the current research status of miRNAs in aging and discuss the possible prospects for clinical applications of targeting miRNAs in senile diseases.

A systematic evidence map of the association between cannabis use and psychosis-related outcomes across the psychosis continuum: An umbrella review of systematic reviews and meta-analyses.

While the legal status and public perception of cannabis are currently changing in many countries, one of the important considerations from a public health viewpoint is its potential association with adverse health outcomes such as the development of psychosis. We conducted an umbrella review of systematic reviews and meta-analyses using the AMSTAR-2 to assess the quality of included reviews. We further created an evidence map to visualize and facilitate the overview of the published evidence synthesis on the association between cannabis use and all psychosis-related outcomes and risk moderators in healthy, high-risk, and clinical populations. Overall, we found 32 systematic reviews and meta-analyses. Based on a synthesis of current evidence, cannabis use is associated with subclinical psychosis states (psychotic-like experiences) and traits (schizotypal personality) in the healthy population, as well as earlier onset and development of psychosis. An association with the clinical-high-risk state for psychosis, attenuated psychosis symptoms and transition to psychosis in this population could not be confirmed. An association between cannabis use and psychosis outcomes in patients with psychotic disorder could solely be confirmed regarding relapse. Whether causal effects underlie those associations has not sufficiently been addressed in the evidence synthesis to date.

Antigenicity and adjuvanticity co-reinforced personalized cell vaccines based on self-adjuvanted hydrogel for post-surgical cancer vaccination.

Cancer vaccine-based postsurgical immunotherapy is emerging as a promising approach in patients following surgical resection for inhibition of tumor recurrence. However, low immunogenicity and insufficient cancer antigens limit the widespread application of postoperative cancer vaccines. Here, we propose a "trash to treasure" cancer vaccine strategy to enhance postsurgical personalized immunotherapy, in which antigenicity and adjuvanticity of purified surgically exfoliated autologous tumors (with whole antigen repertoire) were co-reinforced. In the antigenicity and adjuvanticity co-reinforced personalized vaccine (Angel-Vax), polyriboinosinic: polyribocytidylic acid (pIC) and tumor cells that have undergone immunogenic death are encapsulated in a self-adjuvanted hydrogel formed by cross-linking of mannan and polyethyleneimine. Angel-Vax exhibits an enhanced capacity on antigen-presenting cells stimulation and maturation compared to its individual components in vitro. Immunization with Angel-Vax provokes an efficient systemic cytotoxic T-cell immune response, contributing to the satisfied prophylactic and therapeutic efficacy in mice. Furthermore, when combined with immune checkpoint inhibitors (ICI), Angel-Vax effectively prevented postsurgical tumor recurrence, as evidenced by an increase in median survival of approximately 35% compared with ICI alone. Unlike the cumbersome preparation process of postoperative cancer vaccines, the simple and feasible approach herein may represent a general strategy for various kinds of tumor cell-based antigens in the inhibition of postsurgical tumor relapse by reinforced immunogenicity.

Metformin ameliorates 5-fluorouracil-induced intestinalinjury by inhibiting cellular senescence, inflammation, and oxidative stress.

5-Fluorouracil (5-Fu), which inhibits metabolism, isanessentialpartof the first-line treatment of colorectal cancer but causes severe side effects, including nausea, vomiting, anorexia, and gastrointestinal injury with severe diarrhea, and requires dose reduction or treatment deferral, resulting in a poor prognosis. Metformin has anti-inflammatory effects, but its role in the mechanism of treatment in intestinal injury caused by 5-Fu remains unclear. In our present research, we assessed the impact of metformin on damagetotheintestinefrom5-Fuby inhibiting cellular senescence, intestinalcanal inflammation, and oxidative stress by using HUVECs, HIECs, and male BALB/c mice. It has been found that intestinal damage caused by 5-Fu is associated with the accumulation of senescent cells. Metformin relieved intestinaldamage by suppressing the activity of senescence-ß-galactosidase (SA-ß-gal) and the development of the senescence-associated secretory phenotype (SASP). Furthermore, we observed that the anti-aging effect was closely correlated with mTOR suppression in cell and mouse models. In conclusion, this is the first time that metformin has been able to reduce intestinaldamage related to chemotherapy by inhibiting cellular senescence and oxidative stress.

Belinostat (PXD101) resists UVB irradiation-induced cellular senescence and skin photoaging.

Belinostat (PXD101), a new histone deacetylase inhibitor, has shown good performance in various cancer treatments and has been approved by the FDA for the treatment of recurrent or refractory peripheral T-cell lymphoma (PTCL) in patients with drugs. PXD101 is considered to have certain anti-allergic and anti-inflammatory properties, but its beneficial effects in UVB-induced skin photoaging have not been reported. In a recent study, HacaT cells and C57BL6 mice were used to study the impact of PXD101 on UVB-induced cellular senescence and skin photoaging and to explore their potential mechanisms of action. Studies have shown that PXD101 inhibits UVB-induced HacaT cell senescence, which appears to be achieved by inhibiting activation of the UVB-induced NF-κB/p65 signaling pathway. At the same time, PXD101 inhibits the expression of MMPs. In addition, PXD101 alleviated skin damage on the dorsal skin of mice, reduced skin aging and inflammation, increased collagen fiber synthesis, and restored UVB-induced epidermal thickening. In short, we believe that PXD101 effectively inhibits cellular senescence and skin photoaging caused by UVB exposure, a potential method for developing clinical prevention and treatment of skin aging.

Trifluridine induces HUVECs senescence by inhibiting mTOR-dependent autophagy.

Trifluridine, a key component of trifluridine/tipiracil, is a potential anti-cancer drug that can act effectively on refractory metastatic colorectal cancer. Chemotherapy is important for cancer treatment, but its adverse effects limit its use. Long-term side-effects caused by the drug used during chemotherapy are closely related to the accumulation of cellular senescence. However, the relationship between trifluridine and normal cell aging remains unclear. The purpose of this study is to evaluate whether trifluridine can induce the senescence of human umbilical vein endothelial cells and to explore the possible mechanism. Human umbilical vein endothelial cells were treated with trifluridine, senescence levels were measured via senescence-related acidic ß-galactosidase staining and senescence-associated secretory phenotype levels respectively. Autophagy was assessed by the protein levels of LC3II/LC3I and p62, and LC3 fusion was detected by fluorescence microscopy. Chloroquine diphosphate salt and rapamycin were used to detect the effect of trifluridine on autophagy flux and mTOR signaling pathway. Trifluridine increased the expression of senescence-associated acidic ß-galactosidase and senescence-related secretory phenotype mRNA levels in cells. In addition, also trifluridine induced cellular senescence by inhibiting autophagy and was closely related to the activation of the mTOR signaling pathway, therefore, we believe that trifluridine may be an effective mTOR activator. The findings also provide a new strategy for establishing autophagy or aging models, as well as a new theoretical basis for the use of trifluridine in clinical treatment.

Somatic symptom disorder in the context of Chinese yin-yang culture: A case report and literature review. / 中国阴阳文化背景下的躯体症状障碍1ä¾‹å¹¶æ–‡çŒ®å¤ä¹ .

Somatic symptom disorder (SSD) is a somatic disorder characterized by excessive anxiety over various somatic symptoms for a long time, which makes patients feel very painful and the quality of personal life significantly decreased. Previous studies have shown that there is a connection between the clinical manifestations of SSD patients and their cultural background. The patient in this case report was highly affected by Chinese yin-yang culture, displaying obvious Chinese characteristics.We report a patient with SSD, whose clinical manifestations were mainly sexual dysfunction and mood symptoms which were closely related to the Traditional Chinese culture of Yin and Yang. In this case, Hamilton Anxiety Scale, Hamilton Depression Scale, and International Erectile Function Questionnaire were used to evaluate the patients' anxiety, depression, and sexual function, and the scores were 32, 33, and 9, respectively. The patient was treated with a combination of venlafaxine and mirtazapine. After 5 weeks of treatment, the patient's clinical symptoms improved significantly.The clinical manifestations of some Chinese SSD patients have obvious characteristic relevance to Chinese theory of Yin and Yang, making SSD easily to be misdiagnosed. Therefore, clinicians should pay atlention to this situation. In addition, the combination of venlafaxine and mirtazapine may have a better effect on SSD patients with chronic pain and sexual dysfunction.

Primary chondrocyte exosomes mediate osteoarthritis progression by regulating mitochondrion and immune reactivity.

Aim: We aimed to investigate the proteomics of primary chondrocyte exosomes and the effect of exosomes in osteoarthritis (OA) treatment. Materials & methods: We isolated exosomes from primary chondrocytes cultured in normal (D0) and inflammatory environments induced by IL-1ß and determined the proteomics of these exosomes. Next, we investigated what effect and mechanism D0 chondrocytes exosomes have in OA treatment. Results: There were more proteins that belonged to mitochondrion and were involved in immune system processes in D0 exosomes. Notably, intra-articular administration of D0 exosomes successfully prevented the development of OA. D0 chondrocyte exosomes could restore mitochondrial dysfunction and polarize macrophage response toward an M2 phenotype. Conclusion: Our findings demonstrated that primary chondrocyte exosomes are efficient in OA treatment.

Mesenchymal stem cell-derived exosomes ameliorate intervertebral disc degeneration via anti-oxidant and anti-inflammatory effects.

Excessive oxidative stress and inflammation are the key early events in the development of intervertebral disc degeneration (IVDD). The NACHT, LRR, and PYD domain-containing protein 3 (NLRP3) inflammasome has been identified as the major source of oxidative stress and the inflammatory responses and thus is an attractive therapeutic target for IVDD. However, currently, there are no reports on the use of mesenchymal stem cell (MSC)-derived exosomes to reduce NLRP3 inflammasome expression for IVDD treatment. The present study aimed to investigate the therapeutic effect of exosomes for use as IVDD therapeutics. We first manufactured and evaluated the characteristics of exosomes. Then, we investigated the effects of exosomes on H2O2-induced nucleus pulposus (NP) cell inflammation. Third, we tested the function of exosomes with respect to H2O2-induced ROS production and mitochondrial dysfunction. Finally, the therapeutic effect of exosomes on IVDD was investigated using a rabbit IVDD model. Results showed that exosomes play an anti-inflammatory role in pathological NP cells by suppressing inflammatory mediators and NLRP3 inflammasome activation. Moreover, it was suggested that exosomes might supply mitochondrial proteins to NP cells, and that the damaged mitochondria could be restored with this supplement. Further, in the rabbit IVDD model, exosomes significantly prevented the progression of degenerative changes. Our results confirmed that the NLRP3 inflammasome is an effective target for IVDD treatment and that the injection of exosomes could be a promising therapeutic strategy.

Desktop-stereolithography 3D printing of a radially oriented extracellular matrix/mesenchymal stem cell exosome bioink for osteochondral defect regeneration.

Mitochondrial dysfunction and oxidative stress damage are hallmarks of osteoarthritis (OA). Mesenchymal stem cell (MSC)-derived exosomes are important in intercellular mitochondria communication. However, the use of MSC exosomes for regulating mitochondrial function in OA has not been reported. This study aimed to explore the therapeutic effect of MSC exosomes in a three dimensional (3D) printed scaffold for early OA therapeutics. Methods: We first examined the mitochondria-related proteins in normal and OA human cartilage samples and investigated whether MSC exosomes could enhance mitochondrial biogenesis in vitro. We subsequently designed a bio-scaffold for MSC exosomes delivery and fabricated a 3D printed cartilage extracellular matrix (ECM)/gelatin methacrylate (GelMA)/exosome scaffold with radially oriented channels using desktop-stereolithography technology. Finally, the osteochondral defect repair capacity of the 3D printed scaffold was assessed using a rabbit model. Results: The ECM/GelMA/exosome scaffold effectively restored chondrocyte mitochondrial dysfunction, enhanced chondrocyte migration, and polarized the synovial macrophage response toward an M2 phenotype. The 3D printed scaffold significantly facilitated the cartilage regeneration in the animal model. Conclusion: This study demonstrated that the 3D printed, radially oriented ECM/GelMA/exosome scaffold could be a promising strategy for early OA treatment.

A cancellous bone matrix system with specific mineralisation degrees for mesenchymal stem cell differentiation and bone regeneration.

Bone regenerative therapies have been explored using various biomaterial systems. Notably, collagen biomineralisation is believed to be essential for promoting bone regeneration. However, ideal bone repair materials with an appropriate mineralised matrix, superior osteogenic activity with early vascularisation, and recellularisation properties are still needed. This study aimed to develop a method to subject the decellularised cancellous bone matrix (DCBM) to ultrasound to obtain specific demineralisation to investigate the effects of DCBM with different degrees of mineralisation on proliferation and osteogenic differentiation in bone marrow-derived mesenchymal stem cells (BMSCs) and in repairing femoral bone defects in rabbits. We established an optimised native DCBM mineralisation ECM scaffold for bone regeneration. Upon complete decellularisation of the cancellous bone matrix, DCBMs with specific degrees of mineralisation were obtained. We comprehensively evaluated their bioactive components, minimal immunogenicity, ultra-micro-structural mechanical properties, and degree of mineralisation. Furthermore, specific mineralised DCBMs (obtained by low-temperature rapid ultrasound for 4 and 8 h) had prominent effects in promoting the osteogenic differentiation of BMSCs in vitro. Moreover, more newly formed trabeculae, vessels, and endochondral bone were also detected in the aforementioned groups during early-stage bone repair in vivo. The underlying mechanism might be mineralisation-related regulation and ultra-micro-structural mechanical properties. Thus, the present study shows that specific demineralised DCBM obtained under optimal conditions had superior properties to those of unmineralised or completely demineralised DCBM by promoting MSC osteogenic differentiation and initiating endochondral bone formation and de novo osteogenesis.

Decellularized cartilage as a prospective scaffold for cartilage repair.

Articular cartilage lacks self-healing capacity, and there is no effective therapy facilitating cartilage repair. Osteoarthritis (OA) due to cartilage defects represents large and increasing healthcare burdens worldwide. Nowadays, the generation of scaffolds to preserve bioactive factors and the biophysical environment has received increasing attention. Furthermore, improved decellularization technology has provided novel insights into OA treatment. This review provides a comparative account of different cartilage defect therapies. Furthermore, some recent effective decellularization protocols have been discussed. In particular, this review focuses on the decellularization ratio of each protocol. Moreover, these protocols were compared particularly on the basis of immunogenicity and mechanical functionality. Further, various recellularization methods have been enlisted and the reparative capacity of decellularized cartilage scaffolds is evaluated herein. The advantages and limitations of different recellularization processes have been described herein. This provides a basis for the generation of decellularized cartilage scaffolds, thereby potentially promoting the possibility of decellularization as a clinical therapeutic target.