Arsenic trioxide and p97 inhibitor synergize against acute myeloid leukemia by targeting nascent polypeptides and activating the ZAKα-JNK pathway.

Arsenic trioxide (ATO) has exhibited remarkable efficacy in treating acute promyelocytic leukemia (APL), primarily through promoting the degradation of the PML-RARα fusion protein. However, ATO alone fails to confer any survival benefit to non-APL acute myeloid leukemia (AML) patients and exhibits limited efficacy when used in combination with other agents. Here, we explored the general toxicity mechanisms of ATO in APL and potential drugs that could be combined with ATO to exhibit synergistic lethal effects on other AML. We demonstrated that PML-RARα degradation and ROS upregulation were insufficient to cause APL cell death. Based on the protein synthesis of different AML cells and their sensitivity to ATO, we established a correlation between ATO-induced cell death and protein synthesis. Our findings indicated that ATO induced cell death by damaging nascent polypeptides and causing ribosome stalling, accompanied by the activation of the ZAKα-JNK pathway. Furthermore, ATO-induced stress activated the GCN2-ATF4 pathway, and ribosome-associated quality control cleared damaged proteins with the assistance of p97. Importantly, our data revealed that inhibiting p97 enhanced the effectiveness of ATO in killing AML cells. These explorations paved the way for identifying optimal synthetic lethal drugs to enhance ATO treatment on non-APL AML.

Inhibition of autophagy as a novel treatment for neurofibromatosis type 1 tumors.

Neurofibromatosis type 1 (NF1) is a genetic disorder caused by mutation of the NF1 gene that is associated with various symptoms, including the formation of benign tumors, called neurofibromas, within nerves. Drug treatments are currently limited. The mitogen-activated protein kinase kinase (MEK) inhibitor selumetinib is used for a subset of plexiform neurofibromas (PNs) but is not always effective and can cause side effects. Therefore, there is a clear need to discover new drugs to target NF1-deficient tumor cells. Using a Drosophila cell model of NF1, we performed synthetic lethal screens to identify novel drug targets. We identified 54 gene candidates, which were validated with variable dose analysis as a secondary screen. Pathways associated with five candidates could be targeted using existing drugs. Among these, chloroquine (CQ) and bafilomycin A1, known to target the autophagy pathway, showed the greatest potential for selectively killing NF1-deficient Drosophila cells. When further investigating autophagy-related genes, we found that 14 out of 30 genes tested had a synthetic lethal interaction with NF1. These 14 genes are involved in multiple aspects of the autophagy pathway and can be targeted with additional drugs that mediate the autophagy pathway, although CQ was the most effective. The lethal effect of autophagy inhibitors was conserved in a panel of human NF1-deficient Schwann cell lines, highlighting their translational potential. The effect of CQ was also conserved in a Drosophila NF1 in vivo model and in a xenografted NF1-deficient tumor cell line grown in mice, with CQ treatment resulting in a more significant reduction in tumor growth than selumetinib treatment. Furthermore, combined treatment with CQ and selumetinib resulted in a further reduction in NF1-deficient cell viability. In conclusion, NF1-deficient cells are vulnerable to disruption of the autophagy pathway. This pathway represents a promising target for the treatment of NF1-associated tumors, and we identified CQ as a candidate drug for the treatment of NF1 tumors.

Using metabolic abnormalities of carriers in the neonatal period to evaluate the pathogenicity of variants of uncertain significance in methylmalonic acidemia.

Objective: To accurately verify the pathogenicity of variants of uncertain significance (VUS) in MUT and MMACHC genes through mass spectrometry and silico analysis. Methods: This multicenter retrospective study included 35 participating units (ClinicalTrials.gov ID: NCT06183138). A total of 3,071 newborns (within 7 days of birth) were sorted into carrying pathogenic/likely pathogenic (P/LP) variants and carrying VUS, non-variant groups. Differences in metabolites among the groups were calculated using statistical analyses. Changes in conservatism, free energy, and interaction force of MMUT and MMACHC variants were analyzed using silico analysis. Results: The percentage of those carrying VUS cases was 68.15% (659/967). In the MMUT gene variant, we found that C3, C3/C2, and C3/C0 levels in those carrying the P/LP variant group were higher than those in the non-variant group (p < 0.000). The conservative scores of those carrying the P/LP variant group were >7. C3, C3/C0, and C3/C2 values of newborns carrying VUS (c.1159A>C and c.1286A>G) were significantly higher than those of the non-variant group and the remaining VUS newborns (p < 0.005). The conservative scores of c.1159A>C and c.1286A>G calculated by ConSurf analysis were 9 and 7, respectively. Unfortunately, three MMA patients with c.1159A>C died during the neonatal period; their C3, C3/C0, C3/C2, and MMA levels were significantly higher than those of the controls. Conclusion: Common variants of methylmalonic acidemia in the study population were categorized as VUS. In the neonatal period, the metabolic biomarkers of those carrying the P/LP variant group of the MUT gene were significantly higher than those in the non-variant group. If the metabolic biomarkers of those carrying VUS are also significantly increased, combined with silico analysis the VUS may be elevated to a likely pathogenic variant. The results also suggest that mass spectrometry and silico analysis may be feasible screening methods for verifying the pathogenicity of VUS in other inherited metabolic diseases.

Dezocine as preemptive analgesia alleviates ultrapulse CO2 fractional laser treatment induced pain in patients with acne scars.

BACKGROUND: Ultrapluse CO2 fractional laser technology has emerged as an effective treatment for scar management. However, one drawback of this modality is the pain caused during the procedure. This study aims to explore the efficacy and safety of dezocine (DZC) as preemptive analgesia for reduction of pain induced by ultrapulse CO2 fractional laser treatment for acne scars. METHODS: The study cohort included 78 outpatients with acne scars between February and April 2023. Patients were randomly assigned into three groups with intravenous injection (iv) of DZC prior to laser treatment: (1) control, iv of saline; (2) DZC group 1 (DZC_1), iv of DZC at 0.15 mg/kg; and (3) DZC_2, iv of DZC at 0.20 mg/kg. After 30 min, one session of ultrapulse CO2 fractional laser treatment on acne scars was performed. Hemodynamics, visual analogue scale (VAS), and anxiety visual analog test (AVAT) were monitored prior to, during, and after the procedure. RESULTS: Operative success rates for patients in the control, DZC_1, and DZC_2 groups were 34.6%, 84.6%, and 100%, respectively. DZC administered with either dosage significantly reduced the VAS and AVAT scores of patients in treatment groups as compared with the subjects in the control group during the course of ultrapulse CO2 fractional laser treatment. Patients in DZC_1 and DZC_2 groups did not show any significant difference in hemodynamic parameters, VAS, and AVAT scores. Temporary adverse effects such as nausea and dizziness were observed in some subjects after treatment; the symptoms were quickly dissolved after a rest in supine position. CONCLUSIONS: DZC as preemptive analgesia could effectively reduce pain and anxiety induced by ultrapulse CO2 fractional laser treatment in patients. This study provided an option of preemptive anesthesia to minimize the pain and discomforts associated with laser treatments in clinical practices.

Co-production of fermentable sugars and highly active lignin from eucalyptus via a mild preprocessing with diethylene glycol and chromic chloride.

Eucalyptus was pretreated with diethylene glycol catalyzed by 0.02 mol/L CrCl3 for 10 min, resulting in 91 % delignification and 98 % cellulose recovery, with trace fermentation inhibitors generated. After the mild pretreatment, the accessibility and affinity of cellulase to eucalyptus was enhanced, especially since enzyme adsorption rate increased by 1.6-fold. Therefore, glucose yield of pretreated eucalyptus was 7.9-fold higher than that of untreated eucalyptus after hydrolyzed 48 h, in which the maximum glucose concentration reached 62 g/L from eucalyptus by adding Tween 80. According to the characterization analysis, the structure of the eucalyptus lignin-carbohydrate complexes structure was destroyed during the pretreatment, while lignin fragments was likely reacted with diethylene glycol to form the stabilized aromatic ethers. Moreover, the extracted Deg-lignin exhibited better performances than commercial alkali lignin such as higher fluorescence intensity, less negative surface charge, and lower particle size. The mild pretreatment method with diethylene glycol and CrCl3 provided a promising approach for co-production of fermentable sugars and high activity lignin from lignocellulosic biomass.

Glycated Walnut Meal Peptide-Calcium Chelates: Preparation, Characterization, and Stability.

Finding stable and bioavailable calcium supplements is crucial for addressing calcium deficiency. In this study, glycated peptide-calcium chelates (WMPHs-COS-Ca) were prepared from walnut meal protein hydrolysates (WMPHs) and chitosan oligosaccharides (COSs) through the Maillard reaction, and the structural properties and stability of the WMPHs-COS-Ca were characterized. The results showed that WMPHs and COSs exhibited high binding affinities, with a glycation degree of 64.82%. After glycation, Asp, Lys, and Arg decreased by 2.07%, 0.46%, and 1.06%, respectively, which indicated that these three amino acids are involved in the Maillard reaction. In addition, compared with the WMPHs, the emulsifying ability and emulsion stability of the WMPHs-COS increased by 10.16 mg2/g and 52.73 min, respectively, suggesting that WMPHs-COS have better processing characteristics. After chelation with calcium ions, the calcium chelation rate of peptides with molecular weights less than 1 kDa was the highest (64.88%), and the optimized preparation conditions were 5:1 w/w for WMPH-COS/CaCl2s, with a temperature of 50 °C, a chelation time of 50 min, and a pH of 7.0. Scanning electron microscopy showed that the "bridging role" of WMPHs-COS changed to a loose structure. UV-vis spectroscopy and Fourier transform infrared spectrometry results indicated that the amino nitrogen atoms, carboxyl oxygen atoms, and carbon oxygen atoms in WMPHs-COS chelated with calcium ions, forming WMPHs-COS-Ca. Moreover, WMPHs-COS-Ca was relatively stable at high temperatures and under acidic and alkaline environmental and digestion conditions in the gastrointestinal tract, indicating that WMPHs-COS-Ca have a greater degree of bioavailability.

Effect of succinylation-assisted glycosylation on the structural characteristics, emulsifying, and gel properties of walnut glutenin.

In this study, we examined the effects of various sodium alginate (ALG) concentrations (0.2%-0.8%) on the functional and physicochemical characteristics of succinylated walnut glutenin (GLU-SA). The results showed that acylation decreased the particle size and zeta potential of walnut glutenin (GLU) by 122- and 0.27-fold, respectively. In addition, the protein structure unfolded, providing conditions for glycosylation. After GLU-SA was combined with ALG, the surface hydrophobicity decreased and the net negative charge and disulfide bond content increased. The protein structure was analyzed by FTIR, Endogenous fluorescence spectroscopy, and SEM, and ALG prompted GLU-SA cross-linking to form a stable three-dimensional network structure. The results indicated that dual modification improved the functional properties of the complex, especially its potential protein gel and emulsifying properties. This research provide theoretical support and a technical reference for expanding the application of GLU in the processing of protein and oil products.

Urban airborne PM2.5 induces pulmonary fibrosis through triggering glycolysis and subsequent modification of histone lactylation in macrophages.

Airborne fine particulate matter (PM2.5) can cause pulmonary inflammation and even fibrosis, however, the underlying molecular mechanisms of the pathogenesis of PM2.5 exposure have not been fully appreciated. In the present study, we explored the dynamics of glycolysis and modification of histone lactylation in macrophages induced by PM2.5-exposure in both in vivo and in vitro models. Male C57BL/6 J mice were anesthetized and administrated with PM2.5 by intratracheal instillation once every other day for 4 weeks. Mouse RAW264.7 macrophages and alveolar epithelial MLE-12 cells were treated with PM2.5 for 24 h. We found that PM2.5 significantly increased lactate dehydrogenase (LDH) activities and lactate contents, and up-regulated the mRNA expression of key glycolytic enzymes in the lungs and bronchoalveolar lavage fluids of mice. Moreover, PM2.5 increased the levels of histone lactylation in both PM2.5-exposed lungs and RAW264.7 cells. The pro-fibrotic cytokines secreted from PM2.5-treated RAW264.7 cells triggered epithelial-mesenchymal transition (EMT) in MLE-12 cells through activating transforming growth factor-ß (TGF-ß)/Smad2/3 and VEGFA/ERK pathways. In contrast, LDHA inhibitor (GNE-140) pretreatment effectively alleviated PM2.5-induced pulmonary inflammation and fibrosis via inhibiting glycolysis and subsequent modification of histone lactylation in mice. Thus, our findings suggest that PM2.5-induced glycolysis and subsequent modification of histone lactylation play critical role in the PM2.5-associated pulmonary fibrosis.

Polystyrene microplastic-induced oxidative stress triggers intestinal barrier dysfunction via the NF-κB/NLRP3/IL-1ß/MCLK pathway.

Emerging evidence has demonstrated the association between microplastics (MPs) with a diameter of <5 mm and the risk of intestinal diseases. However, the molecular mechanisms contributing to MP-induced intestinal barrier dysfunction have not been fully appreciated. In this study, C57BL/6 J mice were exposed to polystyrene microplastics (PS-MPs, 0.2, 1 or 5 µm) at 1 mg/kg body weight daily by oral gavage for 28 days. We found that PS-MPs exposure induced oxidative stress and inflammatory cell infiltration in mice colon, leading to an increased expression of pro-inflammatory cytokine. Moreover, there were an increase in intestinal permeability and decrease in mucus secretion, accompanied by downregulation of tight junction (TJ)-related zonula occluden-1 (ZO-1), occluding (OCLN) and claudin-1 (CLDN-1) in mice colon. Especially, 5 µm PS-MPs (PS5)-induced intestinal epithelial TJ barrier damage was more severe than 0.2 µm PS-MPs (PS0.2) and 1 µm PS-MPs (PS1). In vitro experiments indicated that PS5-induced oxidative stress upregulated the expression of nuclear factor kappa B (NF-κB), nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome, and myosin light chain kinase (MLCK). Meanwhile, pre-treatment with the antioxidant NAC, NLRP3 inhibitor MCC950 and MLCK inhibitor ML-7 considerably reduced PS5-triggered reactive oxygen species (ROS) production and inflammatory response, inhibited the activation of the NF-κB/NLRP3/MLCK pathway, and upregulated ZO-1, OCLN and CLDN-1 expression in Caco-2 cells. Taken together, our study demonstrated that PS-MPs cause intestinal barrier dysfunction through the ROS-dependent NF-κB/NLRP3/IL-1ß/MLCK pathway.

[Immune Reconstitution after BTKi Treatment in Chronic Lymphocytic Leukemia].

OBJECTIVE: To analyze the immune reconstitution after BTKi treatment in patients with chronic lymphocytic leukemia (CLL). METHODS: The clinical and laboratorial data of 59 CLL patients admitted from January 2017 to March 2022 in Fujian Medical University Union Hospital were collected and analyzed retrospectively. RESULTS: The median age of 59 CLL patients was 60.5(36-78). After one year of BTKi treatment, the CLL clones (CD5 +/CD19 +) of 51 cases (86.4%) were significantly reduced, in which the number of cloned-B cells decreased significantly from (46±6.1)×109/L to (2.3±0.4)×109/L (P =0.0013). But there was no significant change in the number of non-cloned B cells (CD19 + minus CD5 +/CD19 +). After BTKi treatment, IgA increased significantly from (0.75±0.09)g/L to (1.31±0.1)g/L (P <0.001), while IgG and IgM decreased from (8.1±0.2)g/L and (0.52±0.6)g/L to (7.1±0.1)g/L and (0.47±0.1)g/L, respectively (P <0.001, P =0.002). BTKi treatment resulted in a significant change in T cell subpopulation of CLL patients, which manifested as both a decrease in total number of T cells from (2.1±0.1)×109/L to (1.6±0.4)×109/L and NK/T cells from (0.11±0.1)×109/L to (0.07±0.01)×109/L (P =0.042, P =0.038), both an increase in number of CD4 + cells from (0.15±6.1)×109/L to (0.19±0.4)×109/L and CD8 + cells from (0.27±0.01)×109/L to (0.41±0.08)×109/L (both P <0.001). BTKi treatment also up-regulated the expression of interleukin (IL)-2 while down-regulated IL-4 and interferon (IFN)-γ. However, the expression of IL-6, IL-10, and tumor necrosis factor (TNF)-α did not change significantly. BTKi treatment could also restored the diversity of TCR and BCR in CLL patients, especially obviously in those patients with complete remission (CR) than those with partial remission (PR). Before and after BTKi treatment, Shannon index of TCR in patients with CR was 0.02±0.008 and 0.14±0.001 (P <0.001), while in patients with PR was 0.01±0.03 and 0.05±0.02 (P >0.05), respectively. Shannon index of BCR in patients with CR was 0.19±0.003 and 0.33±0.15 (P <0.001), while in patients with PR was 0.15±0.009 and 0.23±0.18 (P <0.05), respectively. CONCLUSIONS: BTKi treatment can shrink the clone size in CLL patients, promote the expression of IgA, increase the number of functional T cells, and regulate the secretion of cytokines such as IL-2, IL-4, and IFN-γ. BTKi also promote the recovery of diversity of TCR and BCR. BTKi treatment contributes to the reconstitution of immune function in CLL patients.

Comparative clinical study of the modified Broström procedure for the treatment of the anterior talofibular ligament injury-outcomes of the open technique compared to the arthroscopic procedure.

PURPOSE: To observe the clinical efficacy and safety of arthroscopic-modified Broström surgery for the treatment of anterior talofibular ligament injury. METHODS: The clinical data of 51 cases with anterior talofibular ligament injury were retrospectively analyzed, in which 23 patients were treated by arthroscopic-modified Broström surgery (arthroscopic surgery group) and 28 patients were treated by open-modified Broström surgery (open surgery group). The time to surgery, hospital stay, visual analog scale (VAS) scores of ankle pain, American Orthopaedic Foot and Ankle Society (AOFAS) ankle and hindfoot scores, and incidence rate of complications were compared between the two groups. RESULTS: (1) General results: compared with open surgery group, arthroscopic surgery group had shorter time to surgery and hospital stay ((33.8 ± 6.7) min, (42.1 ± 8.5) min, t = 1.468, P = 0.001; (2.2 ± 1.4) d, (5.8 ± 1.6) d, t = 1.975, P = 1.975, P = 0.002). (2) VAS scores of ankle pain: there was an interaction effect between the time and group factors (F = 0.378, P = 0.018); overall, there was no statistically significant difference in VAS scores of ankle pain between the two groups, i.e., there was no grouping effect (F = 1.865, P = 0.163); there was statistically significant difference in VAS score of ankle pain at different time points before and after operation, i.e., there was a time effect (F = 1.675, P = 0.000); the VAS scores of ankle pain showed a decreasing trend with time in both groups, but the decreasing trend was not completely consistent between the two groups ((7.78 ± 1.23), (1.23 ± 1.24), (1.03 ± 0.35), (1.01 ± 0.28), F = 0.568, P = 0.000. (7.45 ± 1.43), (1.45 ± 1.87), (1.23 ± 0.55), (1.04 ± 0.37), F = 1.358, P = 0.000); there was no statistically significant difference in VAS score of ankle joint pain between the two groups six and 12 months before and after surgery (t = 2.987, P = 0.055; t = 1.654, P = 2.542; t = 0.015, P = 0.078); the VAS scores of ankle pain in the arthroscopic surgery group was lower than that in the open surgery group three months after operation (t = 1.267, P = 0.023). (3) AOFAS ankle and hindfoot scores: there was an interaction effect between time and grouping factors (F = 2.693, P = 0.027); overall, there was no statistically significant difference in the AOFAS ankle and hindfoot scores between the two groups, i.e., there was no grouping effect (F = 1.983, P = 0.106); there was statistically significant difference in the AOFAS ankle and hindfoot scores at different time points before and after surgery, i.e., there was a time effect (F = 34.623, P = 0.000); the AOFAS ankle and hindfoot scores of the two groups showed an increasing trend with time, but the increasing trend of the two groups was not completely consistent ((48.19 ± 12.89), (89.20 ± 8.96), (90.24 ± 7.89), (91.34 ± 9.67), F = 25.623, P = 0.000; (49.35 ± 13.28), (86.78 ± 12.34), (88.78 ± 9.78),(91.43 ± 7.98), F = 33.275, P = 0.000); there was no statistically significant difference in the AOFAS ankle and hindfoot scores between the two groups 12 months before/after surgery (t = 2.145，P = 0.056；t = 2.879，P = 0.389); compared with open surgery group, the arthroscopic surgery group had higher AOFAS ankle and hindfoot scores 3/6 months after surgery (t = 1.346, P = 0.014; t = 1.874, P = 0.028). CONCLUSION: For the treatment of anterior talofibular ligament injury, arthroscopic surgery group is superior to open surgery group in ankle pain relief and functional recovery and has shorter operation time and hospital stay compared with open surgery group.

Transplantation of olfactory ensheathing cells can alleviate neuroinflammatory responses in rats with trigeminal neuralgia.

Trigeminal neuralgia (TN) is a common form of facial pain, which primarily manifests as severe pain similar to facial acupuncture and electric shock. Olfactory ensheathing cells (OECs) are glial cells with high bioactivity; these cells are essential for the periodic regeneration of the olfactory nerve and have been utilized for the repair of nerve injuries. A member of the P2X receptor family, P2X7R, is an ion channel type receptor that has been confirmed to participate in various pain response processes. In this study, we transplanted OECs into trigeminal nerve-model rats with distal infraorbital nerve ligation to observe the therapeutic effect of transplanted OECs in rats. Additionally, we utilized the P2X7R-specific inhibitor brilliant blue G (BBG) to study the therapeutic mechanisms of cell transplantation. The facial mechanical pain threshold of these rats significantly increased following cell transplantation. The immunohistochemistry, immunoblotting, and RT-qPCR results demonstrated that the levels of P2X7R, (NOD)-like receptor protein-3 (NLRP3), nuclear factor-κB (NF-κB), interleukin (IL)-1ß, and IL-18 in the trigeminal ganglion of rats treated with OEC transplantation or BBG treatment were significantly lower than those in the injured group without treatment. Overall, our results demonstrate that OEC transplantation can alleviate TN in rats, and it can reduce the expression of P2X7R related inflammatory factors in TN rats, reducing neuroinflammatory response in TG.

Genomic epidemiology reveals early transmission of SARS-CoV-2 and mutational dynamics in Nanning, China.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants are a fatal pathogen resulting in substantial morbidity and mortality, and posing a great threat to human health with epidemics and pandemics. METHODS: Next-generation sequencing (NGS) was performed to investigate the SARS-CoV-2 genomic characterization. Phylogenetic analysis of SARS-CoV-2 genomes was used to probe the evolutionary. Homology protein structure modelling was done to explore potential effect of the mutations. RESULTS: The eighty genome sequences of SARS-CoV-2 obtained from the thirty-nine patients with COVID-19. A novel variant with mutation H625R concomitant with S50L in spike glycoprotein had been identified. Phylogenetic analysis revealed that SARS-CoV-2 variants belong to several distinct lineages. Homology modelling indicated that variant with mutation H625R and S50L increases flexibility of S1 subunit. CONCLUSIONS: SARS-CoV-2 genomes are constantly evolving by accumulation of point mutations. The amino acid H625R in combination with S50L may have a significant impact on the interaction between spike glycoprotein and ACE2.

Analysis of Risk Factors for in-hospital Death in Elderly Patients with TEXAS Stage 3 and 4 Diabetic Foot Ulcers after Tibial Transverse Translation: A Case-Control Study.

OBJECTIVE: Chinese physicians developed the Tibial Transverse Transport (TTT) technique to treat diabetic foot ulcers with more than 90% effective rate. But this method still could not avoid the in-hospital death of patients. This study adopted a case-control study to explore the risk factors of in-hospital death in elderly patients with chronic ischemic diabetic foot after receiving TTT treatment. METHODS: A total of 54 patients were included in the study from January 1, 2017 to April 30, 2021, by being paired with the cases in case group with their demographic data and results of blood routine, liver and kidney function. There were nine patients in case group with six male and three male. Forty-five patients were selected in control group according to gender and diabetes type with 30 male and 15 female. Single factor logics regression analysis was used to explore the risk factors and odd ratios (OR) of in-hospital death in patients. The nomogram and decision curve analysis (DCA) had been done by R Studio software. RESULTS: The study found that age, course of diabetic foot, small dense low-density Lipoprotein (smLDL), homocysteine (Hcy), superoxide dismutase (SOD), and prealbumin (PA) were risk factors for in-hospital death of patients. The smLDL had the highest risk. The nomogram showed that PA accounted for the largest proportion in the death risk factors. The results of DCA proved that above six risk factors were the risk factors for patients with TEXAS Stage 3 and 4 diabetic foot ulcers. CONCLUSION: In the future diagnosis and TTT treatment for diabetic foot ulcers, doctors need to pay close attention to age, course of diabetic foot, smLDL, Hcy, SOD, and PA.

Physicochemical characterization, digestion profile and gut microbiota regulation activity of intracellular polysaccharides from Chlorella zofingiensis.

A number of studies have shown that the polysaccharides from microalgae exhibit diverse biological activities, however, little is known about their digestibility and impact on human gut microbiota. In this study, a simulating digestion and fermentation system were established to investigate the digestibility and fermentation of intracellular polysaccharides from Chlorella zofingiensis (CZIP-S3). The results indicated that CZIP-S3 is a macromolecular polysaccharide composed of mannose, glucose, galactose and rhamnose, consisting of a main chain and two branched repeating units. CZIP-S3 could not be digested in the upper gastrointestinal tract. However, CZIP-S3 could be metabolized into smaller molecules by the gut microbiota. The pH values continuously decrease during fermentation, whereas, the amount of short-chain fatty acids steadily increase. Furthermore, CZIP-S3 could modulate the composition of gut microbiota, via lowering the ratio of Firmicutes/Bacteroidetes and increasing the relative abundance of Bacteroides, Bifidobacterium and Akkermansia. The data suggested that CZIP-S3 could potentially be used as an ingredient for functional foods or prebiotics to improve human health by promoting the relative abundances of beneficial bacteria.

Genomics and nitrogen metabolic characteristics of a novel heterotrophic nitrifying-aerobic denitrifying bacterium Acinetobacter oleivorans AHP123.

A novel aerobic strain of Acinetobacter oleivorans AHP123 was isolated from activated sludge, which could conduct heterotrophic nitrification and denitrification simultaneously. This strain has excellent NH4+-N removal ability, with 97.93% removal rate at 24-hour. To identify the metabolic pathways of this novel strain, genes of gam, glnA, gdhA, gltB, nirB, nasA, nar, nor, glnK and amt were detected by genome analysis. Through RT-qPCR, it was found that the expression of key genes confirmed two possible ways of nitrogen removal in strain AHP123: nitrogen assimilation and heterotrophic nitrification aerobic denitrification (HNAD). However, the absence of some common HNAD genes (amo, nap and nos) suggested that strain AHP123 might have a different HNAD pathway from other HNAD bacteria. Nitrogen balance analysis revealed that strain AHP123 assimilated most of the external nitrogen sources into intracellular nitrogen.

Fractional carbon dioxide vaginal laser treatment of stress urinary incontinence: Remodeling of vaginal tissues and improving pelvic floor structures.

OBJECTIVE: To demonstrate remodeling of vaginal biomechanical and physiological properties using vaginal fractional carbon dioxide (CO2 ) laser treatment of stress urinary incontinence (SUI). MATERIALS AND METHODS: The study cohort included 26 patients with SUI between October 2019 and November 2020. Patients were treated with two sessions of FemTouch vaginal fractional CO2 laser with a one-month interval. Three subjective assessments were administered to all patients: female sexual function index (FSFI), vaginal health index score (VHIS), and international consultation on incontinence questionnaire-short form (ICIQ-SF). Vaginal tissue biopsies were taken from 6 patients before treatment and one-month after the final treatment. Vaginal tactile imaging (VTI) measurements, ultrasonography, and magnetic resonance imaging (MRI) scans were performed before treatment and 10-12-months after treatment in 10, 9, and 6 patients, respectively. RESULTS: The average age of the cohort was 39.5 ± 12.0 years. The overall scores for FSFI, VHIS, and ICIQ-SF significantly improved in patients after each treatment sessions as compared with baseline scores. VTI showed significantly increased pressure resistance of both the anterior and posterior vaginal walls after treatment. Ultrasonography showed significant decreases in bladder neck mobility and urethrovesical angle during the Valsalva maneuver after treatment. MRI scans showed significant decreases in the length of the vaginal anterior wall after treatment. Histological examination confirmed that the laser treatment led to a thicker stratified squamous epithelium layer as compared to the baseline. CONCLUSIONS: Our results demonstrated that vaginal fractional CO2 laser treatment can restore vaginal biomechanical and physiological properties by increasing vaginal tightening and improving pelvic floor structures.

Effects of Alternating Magnetic Fields on the OER of Heterogeneous Core-Shell Structured NiFe2O4@(Ni, Fe)S/P.

Composition optimization, structural design, and introduction of external magnetic fields into the catalytic process can remarkably improve the oxygen evolution reaction (OER) performance of a catalyst. NiFe2O4@(Ni, Fe)S/P materials with a heterogeneous core-shell structure were prepared by the sulfide/phosphorus method based on spinel-structured NiFe2O4 nanomicrospheres. After the sulfide/phosphorus treatment, not only the intrinsic activity of the material and the active surface area were increased but also the charge transfer resistance was reduced due to the internal electric field. The overpotential of NiFe2O4@(Ni, Fe)P at 10 mA cm-2 (iR correction), Tafel slope, and charge transfer resistance were 261 mV, 42 mV dec-1, and 3.163 Ω, respectively. With an alternating magnetic field, the overpotential of NiFe2O4@(Ni, Fe)P at 10 mA cm-2 (without iR correction) declined by 45.5% from 323 mV (0 mT) to 176 mV (4.320 mT). Such enhancement of performance is primarily accounted for the enrichment of the reactive ion OH- on the electrode surface induced by the inductive electric potential derived from the Faraday induction effect of the AMF. This condition increased the electrode potential and thus the charge transfer rate on the one hand and weakened the diffusion of the active substance from the electrolyte to the electrode surface on the other hand. The OER process was dominantly controlled by the charge transfer process under low current conditions. A fast charge transfer rate boosted the OER performance of the catalyst. At high currents, diffusion exerted a significant effect on the OER process and low OH- diffusion rates would lead to a decrease in the OER performance of the catalyst.

Sestrin2 mediates FOXM1 expression to block the EMT process in non-small cell lung cancer through the AMPK/YAP pathway.

Non-small cell lung cancer (NSCLC) is characterized by high incidence and mortality, severely threatening human health. The infinite growth and metastasis of NSCLC cells result in a poor prognosis. Therefore, our study was to investigate the mechanism of Sestrin2 on the epithelial-mesenchymal transition (EMT) process of NSCLC cells. Human embryonic lung fibroblasts, NSCLC cell lines, and nude mice were experimental subjects in this study. qRT-PCR and western blot were performed to evaluate the mRNA and protein expression of genes. CCK-8 and EdU assay were conducted to detect cell proliferation. The scratch test and Transwell assay were applied to examine cell migration and invasion. The bioinformatics analysis and Co-IP assay were employed to predict and consolidate the interaction between YAP and TEAD. We found the expression of Sestrin2 was declined but the expression of YAP was elevated in NSCLC cells. Sestrin2 sufficiency or YAP silencing could effectively impair cell growth and metastasis. Mechanistically, YAP interacted with TEAD to enhance FOXM1 expression. Additionally, the elevation of FOXM1 abolished the inhibitory influences of Sestrin2 sufficiency on NSCLC cell growth, invasion, and EMT process. Eventually, Sestrin2 elevation attenuated tumor growth in mice via modulation of the AMPK/YAP/FOXM1 axis, which was reversed by FOXM1 overexpression. Our consequences suggested Sestrin2 could inhibit the activation of YAP via prompting AMPK phosphorylation and then suppress FOXM1 expression through the interplay between YAP and TEAD to impair the capacities of NSCLC cell proliferation, migration, invasion, and EMT. This study provided a novel mechanism of Sestrin2 in NSCLC.

Enhancing ethylene glycol and ferric chloride pretreatment of rice straw by low-pressure carbon dioxide to improve enzymatic saccharification.

Ethylene glycol and ferric chloride pretreatment assisted by low-pressure carbon dioxide (1 MPa CO2) realized the targeted deconstruction of lignocelluloses at 170 °C for 5 min, achieving 98 % cellulose recovery with removal of 92 % lignin and 90 % hemicellulose. After the pretreatment, the formation of stable platform mono-phenol components would be with the destruction of the lignin-carbohydrate complexes structure, and the surface of rice straw became rough, with a less negative charge and higher specific surface area, while the enzyme adsorption rate increased by 8.1 times. Furthermore, the glucose yield of pretreated straw was remarkably increased by 5.6 times that of the untreated straw, reaching 91 % after hydrolyzed for 48 h. With Tween 80 added in concentrated solid (12 %) hydrolysis at low cellulase loading (3 FPU/g dry substrate), half of the hydrolysis time was shortened than that without Tween 80, with 45 % higher glucose yield.