Uropathogens and clinical manifestations of pyuria-negative urinary tract infections in young infants: A single center cross-sectional study.

BACKGROUND: Urine leukocyte count under microscopy is one of the most frequently used routine screening tests for urinary tract infection (UTI). Nevertheless, it is observed that pyuria is lacking in 10-25% of children with UTI. This study aims to determine the factors related to pyuria-negative UTI in young infants aged under four months old. METHOD: This retrospective cross-sectional study was conducted on 157 patients aged under 4 months old with UTI. All subjects had paired urinalysis and urine culture, which were collected via transurethral catheterization. According to the results of their urinalysis, the patients were then classified as UTI cases with pyuria and UTI cases without pyuria. The clinical characteristics and outcomes of both groups were analyzed. RESULT: Among the 157 UTI patients, the prevalence of pyuria-negative UTI was 44%. Significant risk factors associated with pyuria-negative UTI included non-E.coli pathogens, younger age, shorter duration of fever prior to hospital visit, lower white blood cell (WBC) count upon hospital visit, and absence of microscopic hematuria. CONCLUSIONS: We found that non-E.coli uropathogens were the strongest factor related to pyuria-negative UTI. The absence of pyuria cannot exclude the diagnosis of UTI in young infants, and it's reasonable to perform both urinalysis and urine culture as a part of the assessment of febrile or ill-looking young infants.

Smad2/3/4 complex could undergo liquid liquid phase separation and induce apoptosis through TAT in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) represents one of the most significant causes of mortality due to cancer-related deaths. It has been previously reported that the TGF-ß signaling pathway may be associated with tumor progression. However, the relationship between TGF-ß signaling pathway and HCC remains to be further elucidated. The objective of our research was to investigate the impact of TGF-ß signaling pathway on HCC progression as well as the potential regulatory mechanism involved. METHODS: We conducted a series of bioinformatics analyses to screen and filter the most relevant hub genes associated with HCC. E. coli was utilized to express recombinant protein, and the Ni-NTA column was employed for purification of the target protein. Liquid liquid phase separation (LLPS) of protein in vitro, and fluorescent recovery after photobleaching (FRAP) were utilized to verify whether the target proteins had the ability to drive force LLPS. Western blot and quantitative real-time polymerase chain reaction (qPCR) were utilized to assess gene expression levels. Transcription factor binding sites of DNA were identified by chromatin immunoprecipitation (CHIP) qPCR. Flow cytometry was employed to examine cell apoptosis. Knockdown of target genes was achieved through shRNA. Cell Counting Kit-8 (CCK-8), colony formation assays, and nude mice tumor transplantation were utilized to test cell proliferation ability in vitro and in vivo. RESULTS: We found that Smad2/3/4 complex could regulate tyrosine aminotransferase (TAT) expression, and this regulation could relate to LLPS. CHIP qPCR results showed that the key targeted DNA binding site of Smad2/3/4 complex in TAT promoter region is -1032 to -1182. In addition. CCK-8, colony formation, and nude mice tumor transplantation assays showed that Smad2/3/4 complex could repress cell proliferation through TAT. Flow cytometry assay results showed that Smad2/3/4 complex could increase the apoptosis of hepatoma cells. Western blot results showed that Smad2/3/4 complex would active caspase-9 through TAT, which uncovered the mechanism of Smad2/3/4 complex inducing hepatoma cell apoptosis. CONCLUSION: This study proved that Smad2/3/4 complex could undergo LLPS to active TAT transcription, then active caspase-9 to induce hepatoma cell apoptosis in inhibiting HCC progress. The research further elucidate the relationship between TGF-ß signaling pathway and HCC, which contributes to discover the mechanism of HCC development.

Understanding the Effects of Ligand Configuration on Protoporphyrinogen IX Oxidase with Rationally Designed 3-(N-Phenyluracil)but-2-enoates.

Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) is a promising target for green herbicide discovery. However, the ligand configuration effects on PPO activity were still poorly understood. Herein, we designed 3-(N-phenyluracil)but-2-enoates using our previously developed active fragments exchange and link (AFEL) approach and synthesized a series of novel compounds with nanomolar ranges of Nicotiana tabacum PPO (NtPPO) inhibitory potency and promising herbicidal potency. Our systematic structure-activity relationship investigations showed that the E isomers of 3-(N-phenyluracil)but-2-enoates displayed improved bioactivity than their corresponding Z isomers. Using molecular simulation studies, we found that the E isomers showed a relatively lower entropy change and could sample more stable binding conformation to the receptor than the Z isomers. Our density functional theory (DFT) calculations showed that the E isomers showed higher chemical reactivity and lower electronic chemical potential than their corresponding Z isomers. Compound E-Ic emerged as the optimal compound with a Ki value of 3.0 nM against NtPPO, exhibiting a broader spectrum of weed control than saflufenacil at 37.5-75 g ai/ha and also safe to maize at 75 g ai/ha, which could be considered as a promising lead herbicide for further development.

Risk factors for urinary tract infection in infants with unexplained hyperbilirubinemia: a single center case-control study.

Background: Urinary tract infection (UTI) is a potential cause of neonatal jaundice. Nevertheless, there remains a lack of consensus regarding appropriate screening practices for UTI in infants with hyperbilirubinemia. This study aimed to analyze a group of jaundiced infants to assess the prevalence of UTI, explore potential risk factors, and examine the impact of UTI on the course and severity of neonatal jaundice. Methods: This retrospective case-control study was conducted on 150 jaundiced infants (aged < 8 weeks) without a known etiology in the hyperbilirubinemia work-up. All subjects underwent phototherapy treatment and UTI screening by catheterization. They were then classified into UTI and non-UTI groups based on urine culture results, with a positive urine culture indicating the growth of ≥10,000 colony-forming units. The clinical characteristics and jaundice-related parameters of both groups were analyzed. Results: Among the 150 jaundiced patients, the prevalence of UTI was 29%. There was a significantly higher male predominance in the UTI group, and patients with UTI also had a significantly longer duration of hospitalization compared to those without UTI. Significant risk factors associated with UTI in jaundiced infants included male gender and a peak total bilirubin level higher than 18 mg/dl during hospitalization. The most common pathogens identified in urine culture were Escherichia coli (41.9%) and Enterococcus faecalis (30.2%). Conclusion: In cases of neonatal jaundice where the underlying cause is not evident, screening for UTI should be performed, particularly when associated risk factors or inadequate response to phototherapy is present.

The CXCLs-CXCR2 axis modulates the cross-communication between tumor-associated neutrophils and tumor cells in cervical cancer.

OBJECTIVE: This study aimed to check the expression profile of the C-X-C motif chemokine ligands (CXCLs)-C-X-C motif chemokine receptor 2 (CXCR2) axis in cervical cancer and to explore the cross-talk between cervical cancer cells and neutrophils via CXCLs-CXCR2 axis. METHODS: Available RNA-sequencing data based on bulk tissues and single-cell/nucleus RNA-sequencing data were used for bioinformatic analysis. Cervical cancer cell lines Hela and SiHa cells were utilized for in vitro and in vivo studies. RESULTS: Except for neutrophils, CXCR2 mRNA expression is limited in other types of cells in the cervical tumor microenvironment. CXCLs bind to CXCR2 and are mainly expressed by tumor cells. CXCL1, 2, 3, 5, 6, and 8, which are consistently associated with neutrophil infiltration, are also linked to poor prognosis. SB225002 (a CXCR2 inhibitor) treatment significantly impairs SiHa cell-induced neutrophil migration. CXCL1, CXCL2, CXCL5, or CXCL8 neutralized conditioned medium from SiHa cells have weaker recruiting effects. The conditioned medium of neutrophils from healthy donors can slow cancer cell proliferation. Conditioned medium of tumor-associated neutrophils (TANs) can drastically enhance cervical cancer cell growth in vitro and in vivo. CONCLUSIONS: The CXCLs-CXCR2 axis is critical in neutrophil recruitment and tumor cell proliferation in the cervical cancer microenvironment.

CXCL8 Promotes Endothelial-to-Mesenchymal Transition of Endothelial Cells and Protects Cells from Erastin-Induced Ferroptosis via CXCR2-Mediated Activation of the NF-κB Signaling Pathway.

CXCL8-CXCR1/CXCR2 signaling pathways might form complex crosstalk among different cell types within the ovarian tumor microenvironment, thereby modulating the behaviors of different cells. This study aimed to investigate the expression pattern of CXCL8 in the ovarian tumor microenvironment and its impact on both endothelial-to-mesenchymal transition (EndMT) and ferroptosis of endothelial cells. The human monocytic cell line THP-1 and the human umbilical vein endothelial cell line PUMC-HUVEC-T1 were used to conduct in vitro studies. Erastin was used to induce ferroptosis. Results showed that tumor-associated macrophages are the major source of CXCL8 in the tumor microenvironment. CXCL8 treatment promoted the nucleus entrance of NF-κB p65 and p65 phosphorylation via CXCR2 in endothelial cells, suggesting activated NF-κB signaling. Via the NF-κB signaling pathway, CXCL8 enhanced TGF-ß1-induced EndMT of PUMC-HUVEC-T1 cells and elevated their expression of SLC7A11 and GPX4. These trends were drastically weakened in groups with CXCR2 knockdown or SB225002 treatment. TPCA-1 reversed CXCL8-induced upregulation of SLC7A11 and GPX4. CXCL8 protected endothelial cells from erastin-induced ferroptosis. However, these protective effects were largely canceled when CXCR2 was knocked down. In summary, CXCL8 can activate the NF-κB signaling pathway in endothelial cells in a CXCR2-dependent manner. The CXCL8-CXCR2/NF-κB axis can enhance EndMT and activate SLC7A11 and GPX4 expression, protecting endothelial cells from ferroptosis.

Apparent total tract digestibility and palatability of extruded diets with graded levels of whole soybeans by dogs.

Fat has high energy density and is considered one of the primary energy sources for dogs, however, increasing fat level in dry dog food has been challenging due to the lubrication and limitation of the coating system. The objective was to determine the effect of whole soybeans (WSB) on nutrient digestibility, stool quality, and palatability by dogs. The corn gluten meal, chicken fat, and brewers rice were replaced by WSB at 10, 20, and 30% (WSB10, WSB20, and WSB30, respectively) in the base diet (WSB0). Twelve beagles were randomly assigned. The digestibility trial was duplicated 4 × 4 Latin square design where dogs were allowed a 9-d adaptation followed by a 5-d total fecal collection for each period. Least-square means were analyzed with a single degree of freedom contrasts and significance at α = 0.05. Palatability was determined with a 2-bowl test by 20 beagles for 2 d with each WSB diet compared to the WSB0. First choice preference between two diets and total food consumption were recorded. Individual intake ratios (IR) were calculated (intake of each diet/total intake) for each dog. First choice (FC) was analyzed by a Chi-square probability, and the diet consumption was compared by a Wilcoxon signed rank test and a 2-way analysis of variance. Fecal moisture, output, and defecation frequency increased linearly (P < 0.05) as WSB increased. Apparent total tract digestibility of dry matter, organic matter, crude protein, fat, and gross energy decreased linearly (P < 0.05) as dogs fed the increased level of WSB. The fresh fecal pH in dogs decreased linearly (P < 0.05) as WSB content increased. The acetate, propionate, and the total short-chain fatty acid concentration increased linearly (P < 0.05) while the total branched-chain fatty acid concentration decreased linearly (P < 0.05) as WSB increased. Dogs had greater (P < 0.05) FC for WSB diets than WSB0, but there was no difference among treatments for diet consumption and IR. In conclusion, additional thermal processing before extrusion may improve nutrient digestibility of WSB. The stool quality and palatability were not affected, and fermentation in hindgut increased by WSB by dogs.

Tumor Necrosis Factor-α Promotes the Tumorigenesis, Lymphangiogenesis, and Lymphatic Metastasis in Cervical Cancer via Activating VEGFC-Mediated AKT and ERK Pathways.

Background: Lymphatic metastasis is a common phenomenon of cervical cancer. Tumor necrosis factor-α (TNF-α) was found to be closely associated with lymphatic cancer metastasis. However, the mechanism through which TNF-α regulates lymphatic metastasis in cervical cancer remains unclear. Methods: In this study, cervical cancer cells were cultured in Dulbecco's modified Eagle's medium (DMEM) with or without TNF-α for 48 h, and then the corresponding conditional medium (CM-TNF-α or CM) was collected. The level of vascular endothelial growth factor (VEGFC) in the corresponding CM was then detected using an enzyme-linked immunosorbent assay (ELISA). Next, human lymphatic endothelial cells (HLECs) were cultured in CM-TNF-α or CM for 48 h. Cell viability was measured using the cell counting kit-8 (CCK-8) assay, and angiogenesis was detected using a tube formation assay. Subsequently, the expressions of AKT, p-AKT, ERK, and p-ERK in HLECs were detected using western blotting. In addition, to further investigate the effect of TNF-α on the progression of cervical cancer, a C33A subcutaneous xenograft model was established in vivo. Results: We found that TNF-α significantly stimulated cervical cancer cells to secrete VEGFC. Additionally, the CM collected from the TNF-α-treated cervical cancer cells notably promoted the proliferation, migration, and angiogenesis of HLECs; however, these changes were reversed by MAZ51, a VEGFR3 inhibitor. Moreover, TNF-α obviously elevated D2-40 and VEGFC protein expressions in tumor tissues, promoting lymphangiogenesis and lymphatic metastasis in vivo. Meanwhile, TNF-α markedly upregulated p-AKT and p-ERK expressions in tumor tissues, whereas these changes were reversed by MAZ51. Conclusion: Collectively, TNF-α could promote tumorigenesis, lymphangiogenesis, and lymphatic metastasis in vitro and in vivo in cervical cancer via activating VEGFC-mediated AKT and ERK pathways. These results may provide new directions for the treatment of cervical cancer.

Characterization of genotype IV hepatitis E virus-like particles expressed in E.coli.

HEV (Hepatitis E virus) is an infectious disease transmitted between humans and animals, which poses a severe threat to the biological safety and property throughout the world. The disease is especially severe in patients with potential liver cirrhosis and women during pregnancy. There is no specific and thorough HEV treatment at present. The development of hepatitis E virus vaccine is vital to the prevention of viral hepatitis worldwide. Since HEV cannot grow adequately in vitro, vaccine developed by devitalized virus particles does not work. Exploration of HEV-like structures is essential for the development of functional vaccines against HEV infection. ORF2 encodes the structural proteins of HEV, some of which can automatically assemble into virus-like particles (VLP) in this experiment, the recombinant capsid protein p27 was expressed in E. coli and the VLP formed by p27 was used to immunize mice. The results showed that the VLP formed by recombinant P27 had similar particle size to that of HEV; the immune dose produced by p27 was positively correlated with the immune effect. Compared with other genetic engineering subunit vaccines, P27 protein has a better application prospect.

Impact of oral care modalities on the incidence of ventilator-associated pneumonia in the intensive care unit: A meta-analysis.

BACKGROUND: At present, evidence of the role of oral hygiene in ICU-related pneumonia is rare. The study aimed to evaluate the effectiveness of toothbrush-based oral care in preventing ventilator-associated pneumonia (VAP) in patients with mechanical ventilation in the ICU. METHODS: Ten databases were searched for randomized controlled trials (RCTs) evaluating toothbrush-based oral care for preventing VAP in patients with mechanical ventilation in ICU. Quality assessment and data extraction were independently performed by 2 researchers. The meta-analysis was performed using RevMan 5.3 software. RESULTS: Thirteen RCTs with 657 patients were included. Tooth brushing + 0.2%/0.12% chlorhexidine was associated with reduced incidence of VAP compared to chlorhexidine (OR = 0.63, 95% confidence interval [CI]: 0.43-0.91, P = .01) or tooth brushing + placebo (OR = 0.47, 95% CI: 0.25-0.86, P = .02) in patients with mechanical ventilation in ICU, but was similar to cotton wipe with 0.2% or 0.12% chlorhexidine (OR = 1.33, 95% CI: 0.77-2.29, P = .31). CONCLUSIONS: Tooth brushing combined with chlorhexidine mouthwash can prevent VAP in patients with mechanical ventilation in ICU. There is no advantage of tooth brushing combined with chlorhexidine mouthwash over cotton wipe with chlorhexidine mouthwash for preventing VAP in these patients.

Identification of cuproptosis hub genes contributing to the immune microenvironment in ulcerative colitis using bioinformatic analysis and experimental verification.

Instruction: Ulcerative colitis (UC) can cause a variety of immune-mediated intestinal dysfunctions and is a significant model of inflammatory bowel disease (IBD). Colorectal cancer (CRC) mostly occurs in patients with ulcerative colitis. Cuproptosis is a type of procedural death that is associated with different types of diseases to various degrees. Methods: We used a combination of bioinformatic prediction and experimental verification to study the correlation between copper poisoning and UC. We used the Gene Expression Omnibus database to obtain disease gene expression data and then identified relevant genes involved in various expression levels in normal and UC samples. The Kyoto Encyclopedia of Genes and Genomes pathway analysis was performed to cluster the genes that are highly responsible and find the central interaction in gene crosstalk. Notably, DLD, DLAT, and PDHA1 were present in high-scoring PPI networks. In addition, hub gene expression information in UC tissues was integrated to estimate the relationship between UC copper poisoning and the immune environment. Results: In our study, the expression of DLD, DLAT, and PDHA1 in UC tissues was lower than that in normal tissues. The key genes associated with cuproptosis have therapeutic effects on immune infiltration. We verified the expression of DLD, DLAT, and PDHA1 using real-time quantitative polymerase chain reaction in mouse models of UC induced by DSS. Discussion: Notably, this study clearly indicates that bioinformatic analysis performed to verify the experimental methods provides evidence that cuproptosis is associated with UC. This finding suggests that immune cell infiltration in UC patients is associated with cuproptosis. The key genes associated with cuproptosis can be helpful for discovering the molecular mechanism of UC, thus facilitating the improvement of UC treatment and preventing the associated CRC.

CD27-Expressing Xenoantigen-Expanded Human Regulatory T Cells Are Efficient in Suppressing Xenogeneic Immune Response.

Clinically, xenotransplantation often leads to T-cell-mediated graft rejection. Immunosuppressive agents including polyclonal regulatory T cells (poly-Tregs) promote global immunosuppression, resulting in serious infections and malignancies in patients. Xenoantigen-expanded Tregs (xeno-Tregs) have become a promising immune therapy strategy to protect xenografts with fewer side effects. In this study, we aimed to identify an efficient and stable subset of xeno-Tregs. We enriched CD27+ xeno-Tregs using cell sorting and evaluated their suppressive functions and stability in vitro via mixed lymphocyte reaction (MLR), real-time polymerase chain reaction, inflammatory induction assay, and Western blotting. A STAT5 inhibitor was used to investigate the relationship between the function and stability of CD27+ xeno-Tregs and the JAK3-STAT5 signaling pathway. A humanized xenotransplanted mouse model was used to evaluate the function of CD27+ xeno-Tregs in vivo. Our results show that CD27+ xeno-Tregs express higher levels of Foxp3, cytotoxic T-lymphocyte antigen-4 (CTLA4), and Helios and lower levels of interleukin-17 (IL-17) than their CD27- counterparts. In addition, CD27+ xeno-Tregs showed enhanced suppressive function in xeno-MLR at ratios of 1:4 and 1:16 of Tregs:responder cells. Under inflammatory conditions, a lower percentage of CD27+ xeno-Tregs secretes IL-17 and interferon-γ (IFN-γ). CD27+ xeno-Tregs demonstrated an upregulated JAK3-STAT5 pathway compared with that of CD27- xeno-Tregs and showed decreased Foxp3, Helios, and CTLA4 expression after addition of STAT5 inhibitor. Mice that received porcine skin grafts showed a normal tissue phenotype and less leukocyte infiltration after reconstitution with CD27+ xeno-Tregs. Taken together, these data indicate that CD27+ xeno-Tregs may suppress immune responses in a xenoantigen-specific manner, which might be related to the activation of the JAK3-STAT5 signaling pathway.

Picomolar inhibitor of reverse transcriptase featuring significantly improved metabolic stability

Considering the undesirable metabolic stability of our recently identified NNRTI 5 (t1/2 = 96 min) in human liver microsomes, we directed our efforts to improve its metabolic stability by introducing a new favorable hydroxymethyl side chain to the C-5 position of pyrimidine. This strategy provided a series of novel methylol-biphenyl-diarylpyrimidines with excellent anti-HIV-1 activity. The best compound 9g was endowed with remarkably improved metabolic stability in human liver microsomes (t1/2 = 2754 min), which was about 29-fold longer than that of 5 (t1/2 = 96 min). This compound conferred picomolar inhibition of WT HIV-1 (EC50 = 0.9 nmol/L) and low nanomolar activity against five clinically drug-resistant mutant strains. It maintained particularly low cytotoxicity (CC50 = 264 μmol/L) and good selectivity (SI = 256,438). Molecular docking studies revealed that compound 9g exhibited a more stable conformation than 5 due to the newly constructed hydrogen bond of the hydroxymethyl group with E138. Also, compound 9g was characterized by good safety profiles. It displayed no apparent inhibition of CYP enzymes and hERG. The acute toxicity assay did not cause death and pathological damage in mice at a single dose of 2 g/kg. These findings paved the way for the discovery and development of new-generation anti-HIV-1 drugs.

Establishment of a donor pig for xenotransplantation clinical trials based on the principle of Changsha Communiqué.

Background: Xenotransplantation is a potential way to reduce the shortage of the needed organ grafts for the end-stage disease. Immune rejection, physiological incompatibility and bio-safety are the most critical issues. Methods: To ensure the safety and efficacy of gene editing, second- and third-generation sequencing technologies have allowed us to obtain a clearer genetic background of donor pigs for xenotransplantation. Based on the Changsha Communiqué, the local DPF- excluded lists and DPF donor facility were established in Changsha, China. A pig-to-human islet clinical trial was conducted and overseen by the respective Chinese governmental agency. Results: The DPF standards for pig husbandry eliminated specific pathogens in donor pigs. We have established a PERV-C free, genetic information clean, DPF donor for xenotransplantation. A clinical trial of ten adult patients (9M:1F) with type 1 diabetes who received DPF porcine islet xenotransplantation via the portal vein were performed. Clinical accepted immunosuppressant drugs and autologous Treg were used for controlling immune rejection. No cross-species infection events occurred in this trial, and importantly, no cross-species transmission of PERV was found. Conclusions: Xenotransplantation is a pioneer study and safety is the most important issue. The fundamental principles for establishing xenotransplantation donor pigs should follow the Changsha Communiqué (2008), the second WHO consultation,and the 2018 Changsha Communiqué which would finally help reducing the risks of xenotransplantation.

Pd-Pt-Ru nanozyme with peroxidase-like activity for the detection of total antioxidant capacity.

The design of highly active nanozymes and the establishment of ultra-sensitive bioassays remain a challenge. Therefore, it is necessary to synthesize highly active nanozymes. In this work, a Pd-Pt-Ru (PPR) nanozyme was prepared by atomic coating of the bimetallic nanozyme Pd-Pt. The steady-state kinetics showed that the PPR nanozyme had excellent peroxidase-like activity. Based on this concept, the as-prepared PPR nanozyme was applied to the detection of ascorbic acid (AA) and hydrogen peroxide (H2O2). The linear ranges for ascorbic acid and hydrogen peroxide were 2-12 µM and 5-40 mM, respectively. The limits of detection (LOD) are 1.13 µM and 2.79 mM, respectively. Ascorbic acid was used as a typical model to assay the total antioxidant capacity (TAC) of foods and several herbs. The Fructus Corni extract showed the highest reducing ability. The corresponding extracts were applied for the green synthesis of silver nanoparticles with a size of 167 nm. This study provides a method for the design of highly active nanozymes and the expansion of their applications.

Lumbar Sympathetic Ganglion Block for Cancer-Associated Secondary Lower Limb Lymphedema: A Retrospective Study.

BACKGROUND: Although lower limb lymphedema (LLL) is more or equally as frequent and harmful as upper limb lymphedema after cancer treatment, there are only a few studies on this topic. Cancer-related secondary LLL not only has physical implications, but also affects quality of life among patients who underwent gynecological cancer treatment. Despite numerous studies of various therapies, the optimal treatment for cancer-related LLL is still unknown. OBJECTIVES: We aimed to investigate the efficacy of lumbar sympathetic ganglion block (LSGB) in patients with secondary LLL in the present study. STUDY DESIGN: This study is a retrospective study. SETTING: A single academic hospital, outpatient setting. METHODS: A total of 30 patients with secondary unilateral LLL and failed complex decongestive treatment,  from January 2017 through May 2021, were reviewed for inclusion in this study. The patients underwent fluoroscopy-guided LSGB 2 times with the help of digital subtraction angiography at 3-day intervals. Leg circumference was measured, and the volume of the leg was calculated before surgery, on the first day after the first surgery, on the first day after the second surgery, and on the seventh day after the second surgery. The World Health Organization Quality of Life Instrument Questionnaire scores were monitored before and after LSGB. RESULTS: The leg circumference and volume decreased significantly from baseline after the treatment (P < 0.001). One week after 2 rounds of LSGB, the physical health score, psychological score, and social relationships score were higher than those before treatment (all P < 0.05). There was no difference in the environmental health score (P = 0.2731). LIMITATIONS: This study was limited by its sample size and retrospective observational design. CONCLUSIONS: LSGB can be a safe and effective treatment option for patients with secondary LLL after gynecological cancer treatment.

Enhancing and stabilization of cord blood regulatory T-cell suppressive function by human mesenchymal stem cell (MSC)-derived exosomes.

FOXP3+ regulatory T cells (Tregs) are central to maintaining peripheral tolerance and immune homeostasis. They have the potential to be developed as a cellular therapy to treat various clinical ailments such as autoimmune disorders, inflammatory diseases and to improve transplantation outcomes. However, a major question remains whether Tregs can persist and exert their function effectively in a disease state, where a broad spectrum of inflammatory mediators could inactivate Tregs. In this study, we investigated the potential of mesenchymal stem cell (MSC)-derived exosomes to promote and sustain Tregs function. MSC-conditioned media (MSC-CM) cultured Tregs were more suppressive in both polyclonal and allogeneic responses and were resistant to inflammatory stimulation in vitro compared with the controls. A similar enhancement of Treg function was also observed by culturing Tregs with MSC-derived exosomes alone. The enhanced suppressive activity and stability of Treg cultured in MSC-CM was reduced when exosomes were depleted from MSC-CM. We identified that MSC-derived exosomes could upregulate the expression of LC3(II/I), phosphorylate Jak3 and Stat5 to promote Treg survival, and regulate FOXP3 expression in Tregs. Overall, our study demonstrates that MSC-derived exosomes are capable of enhancing Hucb-Tregs function and stability by activating autophagy and Stat5 signalling pathways. Our findings provide a strong rationale for utilizing MSC-derived exosomes as an effective strategy to enhance Treg function, and improve the overall Tregs-based cell therapy landscape.

Benefit of Belatacept in Cord Blood-Derived Regulatory T Cell-Mediated Suppression of Alloimmune Response.

The role of Regulatory T cells (Tregs) in tolerance induction post-transplantation is well-established, but Tregs adoptive transfer alone without combined immunosuppressants have failed so far in achieving clinical outcomes. Here we applied a set of well-designed criteria to test the influence of commonly used immunosuppressants (belatacept, tacrolimus, and mycophenolate) on cord blood-derived Tregs (CB-Tregs). Our study shows that while none of these immunosuppressants modulated the stability and expression of homing molecules by CB-Tregs, belatacept met all other selective criteria, shown by its ability to enhance CB-Tregs-mediated in vitro suppression of the allogeneic response without affecting their viability, proliferation, mitochondrial metabolism and expression of functional markers. In contrast, treatment with tacrolimus or mycophenolate led to reduced expression of functional molecule GITR in CB-Tregs, impaired their viability, proliferation and mitochondrial metabolism. These findings indicate that belatacept could be considered as a candidate in Tregs-based clinical immunomodulation regimens to induce transplant tolerance.

A micro-environment tuning approach for enhancing the catalytic capabilities of lanthanide containing polyoxometalate in the cyanosilylation of ketones.

The as-synthesized (TBA)8H5[Nd(SiW11O39)2] manifested high catalytic activity for cyanosilylation of ketones, and its catalytic activity could be improved further through rational design of the reaction micro-environment beyond the molecular level, and the corresponding mechanism has been systematically studied.

Magnetic response of Arsenic pollution in a slag covered soil profile close to an abandoned tungsten mine, southern China.

Previous studies indicated serious soil arsenic (As) pollution of large spatial extent related to tungsten mining. We performed systematic analyses of magnetic parameters and As contents of a slag covered soil profile close to the abandoned tungsten mine in southern China, in order to discuss the feasibility of using sensitive, non-destructive, and cost-effective magnetic methods for monitoring the soil arsenic content in such arsenic pollution areas. The results indicate that arsenic sulfide entered from slags into the underlying soil and changed to iron arsenate and moveable arsenic ion. The arsenic ions were transported from the upper to the lower part of the soil profile, leading to more serious arsenic pollution at lower levels of the section. Pedogenesis and oxidation of the entered iron and arsenic sulfide resulted in coexistence of magnetite/maghemite and hematite, with different contributions at depths of 125-195 cm, 60-125 cm, and 0-60 cm. The arsenic content is significant positively correlated with the hematite concentration given by the magnetic parameter HIRM and negatively correlated with the S-300 ratio that measures the relative contributions of magnetite(+maghemite) and hematite. The S-300 ratio is effective for semi-quantification of soil arsenic content, and may be also used for soil arsenic pollution assessment and monitoring in similar settings of tungsten mining.