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Virus-induced genomic remodeling and altered gene expression contribute significantly to cancer development. Some oncogenic viruses such as Human papillomavirus (HPV) specifically trigger certain cancers by integrating into the host’s DNA, disrupting gene regulation linked to cell growth and migration. The effect can be through direct integration of viral genomes into the host genome or through indirect modulation of host cell pathways/proteins by viral proteins. Viral proteins also disrupt key cellular processes like apoptosis and DNA repair by interacting with host molecules, affecting signaling pathways. These disruptions lead to mutation accumulation and tumorigenesis. This review focuses on recent studies exploring virus-mediated genomic structure, altered gene expression, and epigenetic modifications in tumorigenesis.

BackgroundWe explored clinical characteristics and risk factors for mortality in patients with mental disorders combined with severe pneumonia and developed predictive models.MethodsWe retrospectively analyzed the data of 161 patients with mental disorders combined with severe pneumonia in the intensive care unit (ICU) of a psychiatric hospital from May 2020 to February 2023, and divided them into two groups according to whether they died or not, and analyzed their basic characteristics, laboratory results and treatments, etc. We analyzed the risk factors of patients' deaths using logistics regression, established a prediction model, and drew a dynamic nomogram based on the results of the regression analysis. Based on the results of regression analysis, a prediction model was established and a dynamic nomogram was drawn.ResultsThe non-survivor group and the survivor group of patients with mental disorders combined with severe pneumonia were statistically different in terms of age, type of primary mental illness, whether or not they were intubated, whether or not they had been bedridden for a long period in the past, and the Montreal Cognitive Assessment (MoCA) scale, procalcitonin (PCT), albumin (ALB), hemoglobin (Hb), etc. Logistics regression analysis revealed the following: MoCA scale (OR = 0.932, 95% CI:0.872–0.997), age (OR = 1.077, 95%CI:1.029–1.128), PCT (OR = 1.078, 95% CI:10.006–10.155), ALB (OR = 0.971, 95%CI:0.893–1.056), Hb (OR = 0.971, 95% CI: 0.942–0.986) were statistically significant. The ROC curve showed that the model predicted patient death with an area under the curve (AUC) of 0.827 with a sensitivity of 73.4% and a specificity of 80.4%.ConclusionLow MoCA score, age, PCT, and low Hb are independent risk factors for death in patients with mental disorders with severe pneumonia, and the prediction model constructed using these factors showed good predictive efficacy.

Depression is a major neuropsychiatric disease that considerably impacts individuals’ psychosocial function and life quality. Neurotrophic factors are now connected to the pathogenesis of depression, while the definitive neurotrophic basis remains elusive. Besides, phytotherapy is alternative to conventional antidepressants that may minimize undesirable adverse reactions. Thus, further research into the interaction between neurotrophic factors and depression and phytochemicals that repair neurotrophic factors deficit is highly required. This review highlighted the implication of neurotrophic factors in depression, with a focus on the brain-derived neurotrophic factor (BDNF), glial cell line-derived neurotrophic factor (GDNF), vascular endothelial growth factor (VEGF), and nerve growth factor (NGF), and detailed the antidepressant activities of various phytochemicals targeting neurotrophic factors. Additionally, we presented future opportunities for novel diagnostic and therapeutic strategies for depression and provided solutions to challenges in this area to accelerate the clinical translation of neurotrophic factors for the treatment of depression.

Mucormycosis is a conditionally pathogenic fungal disease with high morbidity that mainly affects patients with decreased immunity. Diagnosis relies on the histopathological examination of microorganisms with the typical structure of mucormycetes in tissues and subsequent confirmation via culture. Early detection of causative microorganisms is critical to rapidly administer appropriately targeted antibiotics. Metagenomic next-generation sequencing (mNGS) is an innovative and sensitive technique used to identify pathogenic strains. Here we used mNGS to timely diagnose an infection with Lichtheimia ramosa and Mucor irregularis in two patients with hematologic malignancies; the infections manifested as nasal and cutaneous infections and developed after chemotherapy and small molecule targeted therapy. Following treatment with amphotericin B cholesteryl sulfate complex, the symptoms were reduced significantly, and both patients obtained successful outcomes. Additionally, we searched and summarized the current medical literature on the successful diagnosis of mucormycosis using mNGS. These cases indicated that mNGS, a novel culture-independent method, is capable of rapid, sensitive, and accurate identification of pathogens. mNGS may be a complementary method for the early identification of mucormycosis, allowing for appropriate and timely antibiotic administration and thus improving patient outcomes.

Hexokinase (HXK) is involved in hexose phosphorylation, sugar sensing, and signal transduction, all of which regulate plant growth and adaptation to stresses. Gossypium hirsutum L. is one of the most important fiber crops in the world, however, little is known about the HXKs gene family in G. hirsutum L. We identified 17 GhHXKs from the allotetraploid G. hirsutum L. genome (AADD). G. raimondii (DD) and G. arboreum (AA) are the diploid progenitors of G. hirsutum L. and contributed equally to the At_genome and Dt_genome GhHXKs genes. The chromosomal locations and exon-intron structures of GhHXK genes among cotton species are conservative. Phylogenetic analysis grouped the HXK proteins into four and three groups based on whether they were monocotyledons and dicotyledons, respectively. Duplication event analysis demonstrated that HXKs in G. hirsutum L. primarily originated from segmental duplication, which prior to diploid hybridization. Experiments of qRT-PCR, transcriptome and promoter cis-elements demonstrated that GhHXKs’ promoters have auxin and GA responsive elements that are highly expressed in the fiber initiation and elongation stages, while the promoters contain ABA-, MeJA-, and SA-responsive elements that are highly expressed during the synthesis of the secondary cell wall. We performed a comprehensive analysis of the GhHXK gene family is a vital fiber crop, which lays the foundation for future studies assessing its role in fiber development.

Daily foods contain a great number of self-assembled nanoparticles (NPs) which were incidentally produced during food processing. These food incidental NPs can directly access the human gastrointestinal tract in high frequency and large quantities. Limited reports were focused on whether and how these food incidental NPs affected the gastrointestinal tissues and gut microbiota. In the present study, bone soup and its NPs both significantly ameliorated colitis symptoms in dextran sulfate sodium (DSS)-induced mice and inhibited the release of pro-inflammatory cytokines. They also restored intestinal microbiota dysbiosis by improving the diversity and richness of intestinal microbiota and regulating community composition, such as a remarkable increase in Muribaculaceae, Alistipes, and Alloprevotella, and a decrease in Helicobacter. Moreover, the correlation analysis showed that pro-inflammatory cytokines were negatively correlated with Muribaculaceae, Alloprevotella, and Alistipes, but positively correlated with Helicobacter. These findings suggest that the food incidental NPs can influence human health through regulating the inflammation of the gastrointestinal tissues and the gut microbiota.

Objective: To investigate the immunological mechanism of bone marrow–derived mesenchymal stem cells (BM-MSCs) in inflammatory bowel disease (IBD).Methods: Mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)–induced colitis were intraperitoneally injected with phosphate-buffered saline, BM-MSCs, BM-MSCs with tumor necrosis factor–induced protein 6 (Tnfaip6) knockdown mediated by RNA interference recombinant adenovirus, and BM-MSCs–infected with control adenovirus or recombinant mouse Tnfaip6. The disease activity index, weight loss, and histological scores were recorded. Serum levels of Tnfaip6 and pro- and anti-inflammatory cytokines, including interleukin (IL)-21, tumor necrosis factor-alpha (TNF-α), IL-10 were measured by enzyme-linked immunosorbent assay. The relative expression levels of these cytokines, B-cell lymphoma 6 (BCL-6) and fork-like transcription factor p3 (Foxp3) in the colon were determined by real-time quantitative PCR (RT-qPCR). BCL-6 and Foxp3 are the master regulators of follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr), respectively. The infiltration of Tfh and Tfr in mesenteric lymph nodes (MLNs) and spleens was analyzed by flow cytometry.Results: Compared to the normal control group, the expression levels of BCL-6 and IL-21 in the colon, Tfh infiltration, and ratios of Tfh/Tfr in the MLNs and spleen, and the serum concentrations of IL-21 and TNF-α increased significantly in the colitis model group (p < 0.05). Intraperitoneal injection of BM-MSCs or Tnfaip6 ameliorated weight loss and clinical and histological severity of colitis, downregulated the expression of BCL-6, IL-21, and TNF-α, upregulated the expression of Foxp3, IL-10, and Tnfaip6 (p < 0.05), increased Tfr and reduced the infiltration of Tfh in the MLNs and spleen, and downregulated the Tfh/Tfr ratio (p < 0.05). On the other hand, BM-MSCs lost the therapeutic effect and immune regulatory functions on Tfh and Tfr after Tnfaip6 knockdown.Conclusion: Tfh increase in the inflamed colon, Tfh decrease and Tfr increase during the colitis remission phase, and the imbalance of the Tfh/Tfr ratio is closely related to the progression of IBD. Tnfaip6 secreted by BM-MSCs alleviates IBD by inhibiting Tfh differentiation, promoting Tfr differentiation, and improving the imbalance of Tfh/Tfr in mice.

Depression is an inflammation-associated disease that results in major depression as inflammation increases and progresses. Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and anti-inflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of connexin43 (Cx43) ubiquitin degradation, while Rg1 could upregulate Cx43 expression to attenuate depression. However, whether the ubiquitination of Cx43 is the specific correlation between depression and inflammation, and how Rg1 ameliorates neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (CUS). Moreover, these CUS rats treated with Rg1 exhibited attenuated neuroinflammation, together with the suppression of Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory cytokines and the ubiquitination of Cx43 in lipopolysaccharide-induced glial cells. Furthermore, treatment with ubiquitin-proteasome inhibitor MG132 suppressing the ubiquitination of Cx43 ameliorated lipopolysaccharide-induced neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in CUS-exposed rats; and the main mechanism of the antidepressant-like effects of Rg1 appears to involve protection against neuroinflammation via suppression of Cx43 ubiquitination. In conclusion, Rg1 could ameliorate neuroinflammation via suppression of Cx43 ubiquitination to attenuate depression, which represents the perspective of an innovative therapy of Rg1 in the treatment of inflammation-associated depression.

Chronic stress is an essential factor leading to depression. However, there exist individual differences in people exposed to the same stressful stimuli. Some people display negative psychology and behavior, while others are normal. Given the importance of individual difference, finding differentially expressed proteins in stress-resistant and stress-susceptible groups has great significance for the study of pathogenesis and treatment of depression. In this study, stress-susceptible rats and stress-resilient rats were first distinguished by sucrose preference test. These stress-susceptible rats also displayed depression-like behaviors in forced swimming test and open field test. Then, we employed label-free quantitative proteomics to analyze proteins in the ventral hippocampus. There were 4,848 proteins totally identified. Based on statistical analysis, we found 276 differentially expressed proteins. Bioinformatics analysis revealed that the biological processes of these differential proteins were related to mitochondrion organization, protein localization, coenzyme metabolic process, cerebral cortex tangential migration, vesicle-mediated transport, and so on. The KEGG pathways were mainly involved in metabolic pathways, axon guidance, autophagy, and tight junction. Furthermore, we ultimately found 20 stress-susceptible proteins and two stress-resilient proteins. These stress-related proteins could not only be potential biomarkers for depression diagnosis but also contribute to finding new therapeutic targets and providing personalized medicine.

The Chinese herb couple Fuzi and Ganjiang (FG) has been a classic combination of traditional Chinese medicine that is commonly used clinically in China for nearly 2000 years. Traditional Chinese medicine suggests that FG can treat various ailments, including heart failure, fatigue, gastrointestinal upset, and depression. Neuroinflammation is one of the main pathogenesis of many neurodegenerative diseases in which microglia cells play a critical role in the occurrence and development of neuroinflammation. FG has been clinically proven to have an efficient therapeutic effect on depression and other neurological disorders, but its mechanism remains unknown. Cancer-related fatigue (CRF) is a serious threat to the quality of life of cancer patients and is characterized by both physical and psychological fatigue. Recent studies have found that neuroinflammation is a key inducement leading to the occurrence and development of CRF. Traditional Chinese medicine theory believes that extreme fatigue and depressive symptoms of CRF are related to Yang deficiency, and the application of Yang tonic drugs such as Fuzi and Ganjiang can relieve CRF symptoms, but the underlying mechanisms remain unknown. In order to define whether FG can inhibit CRF depression-like behavior by suppressing neuroinflammation, we conducted a series of experimental studies in vitro and in vivo. According to the UPLC-Q-TOF/MSE results, we speculated that there were 49 compounds in the FG extraction, among which 30 compounds were derived from Fuzi and 19 compounds were derived from Ganjiang. Our research data showed that FG can effectively reduce the production of pro-inflammatory mediators IL-6, TNF-α, ROS, NO, and PGE2 and suppress the expression of iNOS and COX2, which were related to the inhibition of NF-κB/activation of Nrf2/HO-1 signaling pathways. In addition, our research results revealed that FG can improve the depression-like behavior performance of CRF model mice in the tail suspension test, open field test, elevated plus maze test, and forced swimming test, which were associated with the inhibition of the expression of inflammatory mediators iNOS and COX2 in the prefrontal cortex and hippocampus of CRF model mice. Those research results suggested that FG has a satisfactory effect on depression-like behavior of CRF, which was related to the inhibition of neuroinflammation.

Accurate regulation of cell cycle is important for normal tissue development and homeostasis. RCC2 (Regulator of Chromosome Condensation 2) play a role as chromosomal passenger complex (CPC) implicated in all cell cycle phases. RCC2 was initially identified as Ran guanine exchange factor (GEF) for small G proteins. Therefore, RCC2 plays a key role in oncogenesis of most cancers. RCC2 is implicated in Colorectal Cancer (CRC), Lung Adenocarcinoma (LUAD), breast cancer, and ovarian cancer. Expression level of RCC2 protein determines regulation of tumor cell proliferation, invasion, metastasis, and radio-chemotherapeutic resistance. In this review, we explored proteins that interact with RCC2 to modulate tumor development and cancer therapeutic resistance by regulation of cell cycle process through various signaling pathways.

Transcranial ultrasound stimulation (TUS; f < 1 MHz) is a promising approach to non-invasive brain stimulation. Transcranial magneto-acoustic stimulation (TMAS) is a technique of neuromodulation for regulating neuroelectric-activity utilizing a magnetic–acoustic coupling electric field generated by low-intensity ultrasound and magnetic fields. However, both techniques use the physical means of low-intensity ultrasound and can induce the response of the motor cortex. Therefore, it is necessary to distinguish the difference between the two techniques in the regulation of neural activity. This study is the first to quantify the amplitude and response latency of motor cortical electromyography (EMG) in mice induced by TMAS and TUS. The amplitude of EMG (2.73 ± 0.32 mV) induced by TMAS was significantly greater than that induced by TUS (2.22 ± 0.33 mV), and the EMG response latency induced by TMAS (101.25 ± 88.4 ms) was significantly lower than that induced by TUS (181.25 ± 158.4 ms). This shows that TMAS can shorten the response time of nerve activity and enhance the neuromodulation effect of TUS on the motor cortex. This provides a theoretical basis for revealing the physiological mechanisms of TMAS and the treatment of neuropsychiatric diseases using it.

Depression is an inflammation-associated disease that results in major depression as inflammation increases and progresses. Ginsenoside Rg1 (Rg1), the major bioactive ingredient derived from ginseng, possesses remarkable anti-depressant and antiinflammatory effects. Our previous studies showed that the pathogenesis of depression was concomitant with the acceleration of connexin43 (Cx43) ubiquitin degradation, while Rg1 could upregulate Cx43 expression to attenuate depression. However, whether the ubiquitination of Cx43 is the specific correlation between depression and inflammation, and how Rg1 ameliorates neuroinflammation to attenuate depression, are still under investigation. In in vivo experiments, Rg1 treatment significantly ameliorated depression-like behaviors in rats subjected to chronic unpredictable stress (CUS). Moreover, these CUS rats treated with Rg1 exhibited attenuated neuroinflammation, together with the suppression of Cx43 ubiquitination. In in vitro experiments, Rg1 reduced the secretion of inflammatory cytokines and the ubiquitination of Cx43 in lipopolysaccharide-induced glial cells. Furthermore, treatment with ubiquitin-proteasome inhibitor MG132 suppressing the ubiquitination of Cx43 ameliorated lipopolysaccharide-induced neuroinflammation. The results suggest that Rg1 attenuates depression-like behavioral performances in CUSexposed rats; and the main mechanism of the antidepressant-like effects of Rg1 appears to involve protection against neuroinflammation via suppression of Cx43 ubiquitination. In conclusion, Rg1 could ameliorate neuroinflammation via suppression of Cx43 ubiquitination to attenuate depression, which represents the perspective of an innovative therapy of Rg1 in the treatment of inflammation-associated depression. [ABSTRACT FROM AUTHOR]