Methylobacterium flocculans sp. nov., a Floc-Forming Bacterium Isolated from Aquaculture Ponds.

Strain FF17T, a Gram-negative, obligate aerobic, motile, pink-pigmented, and methylotrophic bacterium, was selected for a polyphasic taxonomic investigation due to its capacity for aggregation, or floc formation. The predominant respiratory quinone observed was Q-10, accounting for 83.36% of the total, while the major fatty acids were summed feature 8 (18:1 w6c and/or 18:1 w7c). The major polar lipids included Diphosphatidylglycerol (DPG), phosphatidylglycerol, phosphatidylethanolamine (PE), phosphatidylinositol (PI), and one unknown polar lipid. Phylogenetic analysis showed that strain FF17T was hithermost related to Methylobacterium goesingense iEII3T (99.86%), M. gossipiicola Gh-105 T (99.22%), M. adhaesivum AR27T (98.92%), and M. iners 5317S-33 T (97.27%) based on 16S rRNA gene sequence similarity. A 5,735,273-bp chromosome and six plasmids make up the genome, making it larger than the genomes of the other four Methylobacterium species described above. The digital DNA-DNA hybridization and average nucleotide identity values between strain FF17T and the reference strains were 21.90-28.70 and 77.39-85.04%, respectively. Strain FF17T had a genome DNA G + C content of 68.5 mol%. The analysis of genomes indicated that cellulose apparently plays an important character in the aggregation of Methylobacterium species. Genome annotation revealed the presence of genes involved in assimilatory/dissimilatory nitrate reduction and ammonia assimilation. In conclusion, Strain FF17T is identified as a new species in the Methylobacterium genus, based on analyses of genomics, phylogeny, biochemistry, and fatty acids, and the name Methylobacterium flocculans sp. nov. is proposed. The type strain is FF17T (= MCCC 1K08738T = KCTC 8320 T).

Fractionation, characterization, and assessment of nutritional and immunostimulatory protein-rich polysaccharide-protein complexes isolated from Lentinula edodes mushroom.

This study aimed to fractionate and characterize the protein-rich polysaccharide-protein (PSP) complexes from a well-known edible mushroom, Lentinula edodes, and assess their nutritional and immunostimulatory properties. Crude PSP isolated from the mushroom water extract was purified by anion exchange chromatography, yielding fractions PSP-F1 and PSP-F2 containing 66.1 % and 74.0 % protein, respectively. Both fractions exhibited primarily ß-sheet and random-coil protein structures, though the crude PSP fraction exhibited an additional α-helix structure. On SDS-PAGE, PSP-F1 showed two molecular weight bands, one below 10 kDa and another at 34 kDa, and PSP-F2 showed several bands, one below 10 kDa and others between 34 and 95 kDa. The nutritional value of essential and non-essential amino acid profiles was in the order of PSP-F2 > PSP-F1 > crude PSP; the amino acid ratio coefficient values of the crude PSP, PSP-F1, and PSP-F2 were 63 %, 67 %, and 72 %, respectively. The combination of PS and PSP fractions exhibited stronger immunoactivity than PSP-F1 or PSP-F2 alone. PSP-F2 showed a higher immunostimulatory activity than PSP-F1 in RAW264.7 cell culture. PSP-F2 was also more abundant of easily absorbed high-quality proteins. The results provide useful references for dietary and medicinal uses of PSP fractions in L. edodes and other edible mushrooms.

Tauroursodeoxycholic acid targets HSP90 to promote protein homeostasis and extends healthy lifespan.

As the elderly population expands, the pursuit of therapeutics to reduce morbidity and extend lifespan has become increasingly crucial. As an FDA-approved drug for chronic cholestatic liver diseases, tauroursodeoxycholic acid (TUDCA), a natural bile acid, offers additional health benefits beyond liver protection. Here, we show that TUDCA extends the lifespan and healthspan of C. elegans. Importantly, oral supplementation of TUDCA improves fitness in old mice, including clinically relevant phenotypes, exercise capacity and cognitive function. Consistently, TUDCA treatment drives broad transcriptional changes correlated with anti-aging characteristics. Mechanistically, we discover that TUDCA targets the chaperone HSP90 to promote its protein refolding activity. This collaboration further alleviates aging-induced endoplasmic reticulum (ER) stress and facilitates protein homeostasis, thus offering resistance to aging. In summary, our findings uncover new molecular links between an endogenous metabolite and protein homeostasis, and propose a novel anti-aging strategy that could improve both lifespan and healthspan.

Relationship between TIGIT expression on T cells and the prognosis of patients with hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) combined with targeted therapy and immunotherapy can significantly improve the prognosis of patients with hepatocellular carcinoma (HCC). T-cell immunoreceptor with immunoglobulin and immunoreceptor tyrosine-based inhibitory motif domains (TIGIT) is a novel immunosuppressive molecule. This study aimed to analyze the clinical correlation between TIGIT expression on T cells and patients with HCC. METHODS: Clinical data from 140 patients with HCC were retrospectively collected, and TIGIT expression on T cells was examined in each patient. Patients were subsequently divided into high- and low-expression groups, and their prognosis was analyzed. RESULTS: Patients with a high TIGIT expression on their T cells at baseline had a larger tumor volume, later staging, higher proportion of regulatory T cells, higher blood concentrations of interleukin (IL)-6 and IL-10, and lower interferon-γ concentrations. Following TACE, CD155 concentration decreased; however, TACE did not affect TIGIT expression on T cells. Additionally, among patients receiving TACE combined with apatinib and camrelizumab treatment, patients with a high TIGIT expression on T cells had significantly shorter progression-free survival (PFS) and overall survival times than those of patients in the low-expression group. Patients receiving TACE combined with apatinib and camrelizumab treatment with higher TIGIT expression have shorter PFS time than those receiving TACE combined with apatinib treatment. CONCLUSIONS: Patients with HCC that have a high TIGIT expression on their T cells exhibited poorer baseline characteristics, immunosuppressive status, and prognosis after receiving TACE combined with apatinib and camrelizumab and maybe more suited to receive TACE combined with apatinib treatment instead.

Disruption of branched-chain amino acid homeostasis promotes the progression of DKD via enhancing inflammation and fibrosis-associated epithelial-mesenchymal transition.

BACKGROUND AND AIMS: The disrupted homeostasis of branched-chain amino acids (BCAAs, including leucine, isoleucine, and valine) has been strongly correlated with diabetes with a potential causal role. However, the relationship between BCAAs and diabetic kidney disease (DKD) remains to be established. Here, we show that the elevated BCAAs from BCAAs homeostatic disruption promote DKD progression unexpectedly as an independent risk factor. METHODS AND RESULTS: Similar to other tissues, the suppressed BCAAs catabolic gene expression and elevated BCAAs abundance were detected in the kidneys of type 2 diabetic mice and individuals with DKD. Genetic and nutritional studies demonstrated that the elevated BCAAs from systemic disruption of BCAAs homeostasis promoted the progression of DKD. Of note, the elevated BCAAs promoted DKD progression without exacerbating diabetes in the animal models of type 2 DKD. Mechanistic studies demonstrated that the elevated BCAAs promoted fibrosis-associated epithelial-mesenchymal transition (EMT) by enhancing the activation of proinflammatory macrophages through mTOR signaling. Furthermore, pharmacological enhancement of systemic BCAAs catabolism using small molecule inhibitor attenuated type 2 DKD. Finally, the elevated BCAAs also promoted DKD progression in type 1 diabetic mice without exacerbating diabetes. CONCLUSION: BCAA homeostatic disruption serves as an independent risk factor for DKD and restoring BCAA homeostasis pharmacologically or dietarily represents a promising therapeutic strategy to ameliorate the progression of DKD.

Development of RPA-Cas12a assay for rapid and sensitive detection of Pneumocystis jirovecii.

Pneumocystis jirovecii is a prevalent opportunistic fungal pathogen that can lead to life-threatening Pneumocystis pneumonia in immunocompromised individuals. Given that timely and accurate diagnosis is essential for initiating prompt treatment and enhancing patient outcomes, it is vital to develop a rapid, simple, and sensitive method for P. jirovecii detection. Herein, we exploited a novel detection method for P. jirovecii by combining recombinase polymerase amplification (RPA) of nucleic acids isothermal amplification and the trans cleavage activity of Cas12a. The factors influencing the efficiency of RPA and Cas12a-mediated trans cleavage reaction, such as RPA primer, crRNA, the ratio of crRNA to Cas12a and ssDNA reporter concentration, were optimized. Our RPA-Cas12a-based fluorescent assay can be completed within  30-40 min, comprising a 25-30 min RPA reaction and a 5-10 min trans cleavage reaction. It can achieve a lower detection threshold of 0.5 copies/µL of target DNA with high specificity. Moreover, our RPA-Cas12a-based fluorescent method was examined using 30 artificial samples and demonstrated high accuracy with a diagnostic accuracy of 93.33%. In conclusion, a novel, rapid, sensitive, and cost-effective RPA-Cas12a-based detection method was developed and demonstrates significant potential for on-site detection of P. jirovecii in resource-limited settings.

Three-Dimensional Quantitative Analysis of Internal Limiting Membrane Peeling Related Structural Changes in Retinal Detachment Repair.

PURPOSE: To assess macular microstructural changes associated with internal limiting membrane peeling (ILMP) using 3-dimensional optical coherence tomography (3D-OCT) in primary macula-off rhegmatogenous retinal detachment (RRD) repairs with vitrectomy and silicone oil (SO) tamponade. DESIGN: Retrospective, consecutive, interventional case series. METHODS: Setting: Institutional practice. PATIENT POPULATION: Patients who received primary RRD repair by a single experienced surgeon between January 2017 and December 2021. MAIN OUTCOME MEASURES: In the qualitative comparative analysis, the presence of macular changes among patients who underwent primary RRD repair with (21 eyes) or without ILMP (20 eyes) were observed. Subsequently, a detailed quantitative analysis of ILMP-related microstructural changes in 56 eyes using both 3D and 2D-OCT images were performed. RESULTS: In the qualitative comparative analysis, macular microstructural changes were observed in 95% of ILMP eyes and 5% of non-ILMP eyes (p < .001). In the quantitative analysis, 4 major macular microstructural changes were detected: dimple (75%), dissociated nerve fiber layer (DONFL) (55%), ILM peeling edge thinning (IPET) (64%), and temporal macular groove (TMG) (23%). Dimples (n = 251, average 4.5 ± 5.8 per eye) could be further classified into type I (confined to the inner plexiform layer [IPL]; 73%) and type II (beyond IPL, 27%). The average depth of the deepest dimples was 58 ± 18 µm. The extent of IPET was 6.0 ± 3.7 clock hours. The average length of TMG was 1.8 ± 0.4 mm. Comparing to unoperated fellow eyes, the eyes after ILMP showed decreased inner temporal over nasal retinal thickness ratio (0.86 ± 0.07 versus 0.96 ± 0.03, p < .001), shorter disc-fovea distance (4.61 ± 0.32 µm versus 4.78 ± 0.37 µm, p = .041), and wider retinal vein trajectories (c' = 2.48 ± 0.84 vs 3.39 ± 1.61, p = .002). CONCLUSIONS: Macular microstructural changes are common after ILMP in RRD repair, encompassing both focal changes (dimples, DONFL) and zonal changes (IPET, TMG). DONFL and dimples may be part of a continuum of findings stemming from the same mechanism. IPET and TMG are the results of macular tissue shift due to contracture of the optic disc and neurovascular bundle.

[Efficacy and Safety of Reduced Dose Azacitidine in the Treatment of Elderly Patients with Myelodysplastic Syndromes].

OBJECTIVE: To analyze the efficacy and safety of low-dose azacitidine in the treatment of senile myelodysplastic syndromes (MDS). METHODS: A total of 92 elderly MDS patients who were initially diagnosed in the Huaibei Miners General Hospital and the Affiliated Hospital of Xuzhou Medical University from January 2018 to June 2022 were randomly divided into the observation group and the control group with 46 patients in each group. The observation group received a low dose of azacitidine 100 mg/d, d1-7, 28 days as a course of treatment, 6 courses in total, and the control group received a standard dose of azacitidine 75 mg(m2·d), d1-7, 28 days as a course of treatment, a total of 6 courses of treatment. The clinical efficacy, overall survival (OS) and adverse reactions of the two groups of patients were observed. RESULTS: There was no statistically significant difference in the clinical data between the two groups (P >0.05). After treatment, the hemoglobin and platelet levels of the two groups of patients were significantly higher than before treatment in each group (P < 0.05). There was no statistically significant difference in leukocyte, hemoglobin and platelet levels between patients in the observation group and control group (P >0.05). The number of cases with complete remission, partial remission, hematological remission, disease stabilization and disease progression in the observation group were 4, 10, 22, 6 and 4, respectively, with a total effective rate of 78.26%. The numbers of cases with complete remission, partial remission, hematological remission, disease stabilization and disease progression in control group were 8, 12, 18, 4 and 4, respectively, with a total effective rate of 82.61%. The total effective rate of patients in the observation group was slightly lower than that of the control group(χ2=0.457, P =0.254). There was no significant difference between the two treatment schemes in the treatment of patients with blood transfusion dependence and patients with low risk, medium risk and high risk (P >0.05). It takes 4 and 6 courses of treatment to achieve the best treatment response in the control group and observation group respectively. There was no significant difference in OS between the two groups (P >0.05). In the observation group, there were 4, 6 and 2 cases of infection, III-IV degree myelosuppression and gastrointestinal reaction, respectively, with the incidence rate of adverse events being 26.09%. In the control group, there were 6, 16 and 6 cases of infection, III-IV degree myelosuppression and gastrointestinal reaction, respectively, with the adverse event rate was 60.87%. The incidence of adverse events in the control group was significantly higher than that in the observation group (χ2=7.095, P =0.036). CONCLUSION: Elderly patients with MDS have poor tolerance to chemotherapy. Reducing azacitidine in the treatment of elderly MDS patients shows good efficacy and safety.

Comparison of One-Year Outcome of Intravitreal Aflibercept with or without Photodynamic Therapy for Polypoidal Choroidal Vasculopathy.

Background and Objectives: Our study compared the visual and anatomical outcomes of polypoidal choroidal vasculopathy (PCV) patients receiving intravitreal aflibercept (IVA) with or without photodynamic therapy (PDT) over 12 months. Materials and Methods: This retrospective study was performed for 60 eyes from 60 patients with treatment-naïve PCV. Thirty eyes were treated using IVA monotherapy (IVA group), and thirty eyes were treated using a combination of IVA with PDT (IVA/PDT group). The baseline characteristics, treatment outcomes, and retreatment rates were compared between the two groups over a one-year follow-up period. Results: The best-corrected visual acuity (BCVA) was found to have improved significantly in the IVA/PDT group at every 3-month visit. However, no significant BCVA improvement was observed in the IVA group. A significantly lower retreatment rate and higher dry macula rate were found in the IVA/PDT group than that in the IVA group. In the entire population of the study, a better baseline vision and younger age were associated with better final visual outcomes. Retreatment was associated with poor baseline BCVA and IVA monotherapy. Conclusions: The combination of IVA and PDT may offer superior visual improvement and a higher dry macula rate compared to IVA monotherapy in the treatment of PCV patients while requiring fewer retreatments over 12 months.

Clinical characteristics of overlapping syndrome in patients with GFAP-IgG and MOG-IgG: a case series of 8 patients and literature review.

OBJECTIVE: The overlapping syndrome of anti-GFAP and anti-MOG antibodies is extremely rare. This retrospective study reports 8 adult cases of the GFAP-MOG overlapping syndrome. METHODS: We reviewed the clinical characteristics of 8 adult patients with the GFAP-MOG overlapping syndrome from Jan 2019 and Sep 2023 at the Third Affiliated Hospital, Sun Yat-sen University. Moreover, we searched the literature and included all case reports with this overlapping syndrome since 2018 on PubMed. RESULTS: The predominant clinical syndrome was meningoencephalomyelitis (5/8), followed by meningoencephalitis (2/8), and myelitis (1/8). Five patients had a flu-like prodromal symptom or diarrhea. No neoplasms were found in these patients. Regarding brain MRI, T2-weighted/fluid-attenuated inversion recovery hyperintensities were in 7 patients and leptomeningeal enhancement was in 4 patients. However, only one patient had periventricular radial linear enhancement. Besides, two patients had large space-occupying lesions. For spinal MRI, T2-hyperintensities were observed in 4 patients, in which 3 patients had longitudinally extensive lesions. All patients were treated with immunotherapy, the median follow-up period was 18 months (range, 3-36 months). Three patients presented relapses during the follow-up, but all cases recovered to mRS scores ≤ 2 at last follow-up. In addition, we also reviewed 14 cases (including 7 adults and 7 children) with this overlapping syndrome by literature review. CONCLUSION: Our findings provide data to understand the clinical features and prognosis of the GFAP-MOG overlapping syndrome. Recognizing this overlapping syndrome will expand our knowledge, allowing for better management of these patients.

Simulated human digestion and fermentation of a high-molecular weight polysaccharide from Lentinula edodes mushroom and protective effects on intestinal barrier.

Lentinula edodes (Shiitake) is an important edible mushroom and polysaccharides are its major constituents with proven health benefits. The study was to investigate the gut bacterial fermentation and subsequent effects on gut barrier function of a glucan-rich polysaccharide, LePS40 precipitated from the mushroom water extract with 40 % (v/v) ethanol. LePS40 consisted of a ß-(1→3)-glucan main chain with substitution in the C-6 position with side chains mainly composed of (1 → 6)-linked ß-Glcp residues, (1 → 6)-linked α-Galp residues and terminal residues of ß-Glcp. LePS40 was found highly resistant to digestive enzymes and gastric acid in simulated human gastrointestinal tract, but highly fermentable during in vitro human fecal fermentation. The fecal fermentation degradation of LePS40 appeared to selectively break the glucoside linkage in view of the dramatic decrease in the glucose molar ratio (12.68 to 1.07). Compared with the prebiotic reference FOS, LePS40 led to much higher levels of butyric, and propionic acid and a lower level of acetic acid. Moreover, LePS40 enhanced the abundance of some beneficial bacterial populations, but decreased the bacteria possibly linked with fatty-liver disease and colorectal cancer. Furthermore, the fecal fermentation products of LePS40 showed a potential protective effect on intestinal barrier function against inflammatory damage in Caco-2/Raw264.7 co-culture model. These findings suggest the potential of LePS40 for improvement of gut health through modulation of gut microbiota.

The impact of a student death doula service-learning experience in palliative care settings on nursing students: A pilot mixed-methods study.

Through a mixed-methods approach (randomized controlled trial and thematic analysis of pre and post-service-learning reflections), this study evaluated the impact of a student death doula service-learning experience on nursing students' palliative competencies and learning experiences. The intervention group underwent a 2-day student death doula training workshop followed by a 6-month service-learning experience, while the control group received standard palliative care education. Attitudes toward the care of the dying significantly improved for the intervention group but not for compassion competence and palliative care knowledge. Six themes were developed: (1) Motivations for being a student death doula, (2) Improved perceptions of palliative care patients, (3) Perceptions of a good death, (4) Confidence in caring for palliative care patients, (5) Understanding the multifaceted nature of palliative care, and (6) Joys and challenges during service-learning. Service-learning helped students to understand palliative care patients and acquire confidence in engaging with them.

Residential Wood Burning and Vehicle Emissions as Major Sources of Environmentally Persistent Free Radicals in Fairbanks, Alaska.

Environmentally persistent free radicals (EPFRs) play an important role in aerosol effects on air quality and public health, but their atmospheric abundance and sources are poorly understood. We measured EPFRs contained in PM2.5 collected in Fairbanks, Alaska, in winter 2022. We find that EPFR concentrations were enhanced during surface-based inversion and correlate strongly with incomplete combustion markers, including carbon monoxide and elemental carbon (R2 > 0.75). EPFRs exhibit moderately good correlations with PAHs, biomass burning organic aerosols, and potassium (R2 > 0.4). We also observe strong correlations of EPFRs with hydrocarbon-like organic aerosols, Fe and Ti (R2 > 0.6), and single-particle mass spectrometry measurements reveal internal mixing of PAHs, with potassium and iron. These results suggest that residential wood burning and vehicle tailpipes are major sources of EPFRs and nontailpipe emissions, such as brake wear and road dust, may contribute to the stabilization of EPFRs. Exposure to the observed EPFR concentrations (18 ± 12 pmol m-3) would be equivalent to smoking ∼0.4-1 cigarette daily. Very strong correlations (R2 > 0.8) of EPFR with hydroxyl radical formation in surrogate lung fluid indicate that exposure to EPFRs may induce oxidative stress in the human respiratory tract.

Adaptive Size Evolution of an MOFs-in-MOF Nanovehicle for Enhanced Nucleus-Targeted Tumor Chemotherapy.

A metal-organic frameworks (MOFs)-in-MOF nanovehicle (160 nm), which was constructed with newly prepared ultrasmall Cu(I)Cu(II)-BTC MOFs (UCMs, 2.95 nm) loaded with doxorubicin (DOX) and a nuclear localization signal (NLS) peptide as multicores (UCMDNs) and ZIF-8 as the shell MOF, was proposed to cross layers of biological barriers with adaptive size evolution capacity for achieving efficient nucleus-targeted drug delivery. It first enhanced tumor tissue penetration through its larger nanosize effect. Then the acidic tumor environment made the ZIF-8 shell degrade, releasing small-sized UCMDNs to enter into the cell and into the nucleus under the guidance of NLS. Furthermore, due to the distinct surface structural characteristics of UCMs, UCMDNs remained stable in the cytoplasm and collapsed in the nucleus due to the DOX-DNA interaction to deliver DOX precisely. It showed superior performance in the nucleus-directed delivery of DOX (delivery efficiency up to 56.7%) and a high tumor growth inhibition rate (96.4%), offering promising prospects in tumor chemotherapy.

Analysis of spiritual well-being status and influencing factors in patients with esophageal cancer: a cross-sectional study.

OBJECTIVE: To understand the status of spiritual well-being in patients with esophageal cancer and analyze its influencing factors. METHODS: A total of 187 patients with esophageal cancer (EC) from two grade A hospitals in Chengdu were selected and investigated by general data questionnaire, chronic disease function evaluation-spirituality scale 12 (FACIT-SP-12), general well-being scale (GWB), and Anderson symptom assessment scale gastrointestinal tract (MDASI-GI). RESULTS: The spiritual well-being score of patients with esophageal cancer was (25.13 ± 9.63). Spiritual well-being was positively correlated with general well-being and negatively correlated with symptom burden (P < 0.01). The results of multiple stepwise linear regression analysis showed that hobbies, disease stage, general well-being, and symptom burden were the main influencing factors for the spiritual well-being of esophageal cancer patients (P < 0.05), explaining 49.0% of the total variation. CONCLUSIONS: The spiritual well-being of patients with esophageal cancer is lower than the middle level, In addition, whether there is a hobby in life, disease stage, subjective well-being, and symptom burden are the main factors affecting the spiritual well-being of patients with EC. It is suggested that medical staff should take targeted care measures according to the influencing factors, so as to improve the spiritual well-being level of patients and improve the quality of life of patients.

A novel bispecific antibody targeting two overlapping epitopes in RBD improves neutralizing potency and breadth against SARS-CoV-2.

SARS-CoV-2 has been evolving into a large number of variants, including the highly pathogenic Delta variant, and the currently prevalent Omicron subvariants with extensive evasion capability, which raises an urgent need to develop new broad-spectrum neutralizing antibodies. Herein, we engineer two IgG-(scFv)2 form bispecific antibodies with overlapping epitopes (bsAb1) or non-overlapping epitopes (bsAb2). Both bsAbs are significantly superior to the parental monoclonal antibodies in terms of their antigen-binding and virus-neutralizing activities against all tested circulating SARS-CoV-2 variants including currently dominant JN.1. The bsAb1 can efficiently neutralize all variants insensitive to parental monoclonal antibodies or the cocktail with IC50 lower than 20 ng/mL, even slightly better than bsAb2. Furthermore, the cryo-EM structures of bsAb1 in complex with the Omicron spike protein revealed that bsAb1 with overlapping epitopes effectively locked the S protein, which accounts for its conserved neutralization against Omicron variants. The bispecific antibody strategy engineered from overlapping epitopes provides a novel solution for dealing with viral immune evasion.

Immune effect and prognosis of transcatheter arterial chemoembolization and tyrosine kinase inhibitors therapy in patients with hepatocellular carcinoma.

BACKGROUND: The combination of transcatheter arterial chemoembolization (TACE) and tyrosine kinase inhibitors (TKIs) has shown broad prospects in prolonging the survival of patients with hepatocellular carcinoma (HCC). TACE and TKIs can affect the immune microenvironment in patients with HCC. AIM: To determine the overall effects and differences between TACE and different TKIs combinations on the immune microenvironment. METHODS: Data and immune cell profile test results from 213 HCC patients treated with TACE combined with apatinib, lenvatinib, sorafenib, or donafenib before and after 3 wk of treatment were collected. Monocytes were co-cultured with LM3 liver cancer cells, and their ability to inhibit cancer cell growth was analyzed using the MTT method and a nude mouse subcutaneous tumorigenesis experiment. Simulated combined therapy was done using an in situ liver cancer C57BL/6 male mouse model, and the immune response of tumor tissues was analyzed using immunohistochemistry. RESULTS: Compared to before combination therapy, the proportion of programmed cell death protein 1 (PD-1)+ mononuclear cells and the number of CD4+ T cells decreased in the TACE + apatinib group, while the number of absolute count of CD4+ and CD8+ T cells increased in the TACE + lenvatinib group. Furthermore, the number of regulatory cells decreased in the TACE + donafenib group, whereas the number of CD8+ T and natural killer cells increased. Additionally, monocytes in the TACE combined with donafenib or lenvatinib groups had a stronger ability to inhibit cancer cell growth than those in the other groups. Combining TACE with donafenib or lenvatinib increased CD8+ T cell infiltration into the tumor tissue. In addition, the proportion of PD-1+ in CD8+ cells, absolute CD8+ T lymphocyte count, and regulatory T cells proportion were independent prognostic factors affecting the survival time of patients with HCC. CONCLUSION: TACE, in combination with different TKIs, produces different immune responses. Specifically, TACE combined with donafenib or lenvatinib may induce strong anti-tumor immune responses.

The artistic image processing for visual healing in smart city.

This study investigates the processing methods of artistic images within the context of Smart city (SC) initiatives, focusing on the visual healing effects of artistic image processing to enhance urban residents' mental health and quality of life. Firstly, it examines the role of artistic image processing techniques in visual healing. Secondly, deep learning technology is introduced and improved, proposing the overlapping segmentation vision transformer (OSViT) for image blocks, and further integrating the bidirectional long short-term memory (BiLSTM) algorithm. An innovative artistic image processing and classification recognition model based on OSViT-BiLSTM is then constructed. Finally, the visual healing effect of the processed art images in different scenes is analyzed. The results demonstrate that the proposed model achieves a classification recognition accuracy of 92.9% for art images, which is at least 6.9% higher than that of other existing model algorithms. Additionally, over 90% of users report satisfaction with the visual healing effects of the artistic images. Therefore, it is found that the proposed model can accurately identify artistic images, enhance their beauty and artistry, and improve the visual healing effect. This study provides an experimental reference for incorporating visual healing into SC initiatives.

HIV Incidence and Transactional Sex Among Men Who Have Sex With Men in Ningbo, China: Prospective Cohort Study Using a WeChat-Based Platform.

Background: Sexual transmission among men who have sex with men (MSM) has become the major HIV transmission route. However, limited research has been conducted to investigate the association between transactional sex (TS) and HIV incidence in China. Objective: This study aims to investigate HIV incidence and distinguish sociodemographic and sexual behavioral risk factors associated with HIV incidence among MSM who engage in TS (MSM-TS) in China. Methods: We conducted a prospective cohort study using a WeChat-based platform to evaluate HIV incidence among Chinese MSM, including MSM-TS in Ningbo, recruited from July 2019 until June 2022. At each visit, participants completed a questionnaire and scheduled an appointment for HIV counseling and testing on the WeChat-based platform before undergoing offline HIV tests. HIV incidence density was calculated as the number of HIV seroconversions divided by person-years (PYs) of follow-up, and univariate and multivariate Cox proportional hazards regression was conducted to identify factors associated with HIV incidence. Results: A total of 932 participants contributed 630.9 PYs of follow-up, and 25 HIV seroconversions were observed during the study period, resulting in an estimated HIV incidence of 4.0 (95% CI 2.7-5.8) per 100 PYs. The HIV incidence among MSM-TS was 18.4 (95% CI 8.7-34.7) per 100 PYs, which was significantly higher than the incidence of 3.2 (95% CI 2.1-5.0) per 100 PYs among MSM who do not engage in TS. After adjusting for sociodemographic characteristics, factors associated with HIV acquisition were MSM-TS (adjusted hazard ratio [aHR] 3.93, 95% CI 1.29-11.93), having unprotected sex with men (aHR 10.35, 95% CI 2.25-47.69), and having multiple male sex partners (aHR 3.43, 95% CI 1.22-9.64) in the past 6 months. Conclusions: This study found a high incidence of HIV among MSM-TS in Ningbo, China. The risk factors associated with HIV incidence include TS, having unprotected sex with men, and having multiple male sex partners. These findings emphasize the need for developing targeted interventions and providing comprehensive medical care, HIV testing, and preexposure prophylaxis for MSM, particularly those who engage in TS.

[Mongolian medicine Naru-3 reduces neuroinflammation in maintenance stage of neuropathic pain by inhibiting astrocyte activation].

Neuropathic pain(NP) is difficult to be treated since it has similar phenotypes but different pathogenesis in different pathological stages. Targeted intervention of the core regulatory elements at different pathological stages of NP has become a new direction of drug research and development in recent years and provides the possibility for the treatment of NP. The Mongolian medicine Naru-3(NR-3) is effective in the treatment of sciatica and trigeminal neuralgia, the mechanisms of which remain unknown. On the basis of the previous study of the priming stage, this study established the mouse model of spinal nerve ligation(SNL) and measured the changes of pain thresholds by behavioral tests. The network analysis, Western blot, immunofluorescence assay, ELISA, and agonist/antagonist were employed to decipher the mechanism of NR-3 in the treatment of NP in the maintenance stage. The results showed that NR-3 increased the mechanical and thermal pain thresholds of SNL mice, while it had no significant effect on the basal pain threshold of normal mice. NR-3 may relieve the pain in the maintenance stage of NP by blocking the matrix metalloproteinase 2(MMP2)/interleukin-1ß(IL-1ß) pathway in the astrocytes of the dorsal root ganglion(DRG) and spinal cord. The findings have enriched the biological connotation of NR-3 in the treatment of the maintenance stage of NP and provide reference for the rational use of this medicine in clinical practice.