A causal link between circulating leukocytes and three major urologic cancers: a mendelian randomization investigation.

Purpose: This study aimed to explore the influence of serum leukocytes on urologic cancers (UC) using observation-based investigations. In the present study, Mendelian randomization (MR) was employed to assess the link between leukocyte count (LC) and the risk of UC development. Methods: Five LC and three major UC patient prognoses were obtained for MR analysis from genome-wide association studies (GWAS). Furthermore, in order to evaluate reverse causality, bidirectional studies were conducted. Finally, a sensitivity analysis using multiple methods was carried out. Results: There was no significant correlation found in the genetic assessment of differential LC between the co-occurrence of bladder cancer (BCA) and renal cell carcinoma (RCC). Conversely, an individual 1-standard deviation (SD) rise in neutrophil count was strongly linked to a 9.3% elevation in prostate cancer (PCA) risk ([odd ratio]OR = 1.093, 95% [confidence interval]CI = 0.864-1.383, p = 0.002). Reverse MR analysis suggested that PCA was unlikely to cause changes in neutrophil count. Additional sensitivity studies revealed that the outcomes of all MR evaluations were similar, and there was no horizontal pleiotropy. Primary MR analysis using inverse-variance weighted (IVW) revealed that differential lymphocyte count significantly influenced RCC risk (OR = 1.162, 95%CI = 0.918-1.470, p = 0.001). Moreover, altered basophil count also affected BCA risk (OR = 1.249, 95% CI = 0.904-1.725, p = 0.018). Nonetheless, these causal associations were not significant in the sensitivity analysis. Conclusion: In summary, the results revealed that increased neutrophil counts represent a significant PCA risk factor. The current research indicates a significant relationship between immune cell activity and the cause of UC.

Predicting 2-year neurodevelopmental outcomes in preterm infants using multimodal structural brain magnetic resonance imaging with local connectivity.

The neurodevelopmental outcomes of preterm infants can be stratified based on the level of prematurity. We explored brain structural networks in extremely preterm (EP; < 28 weeks of gestation) and very-to-late (V-LP; ≥ 28 and < 37 weeks of gestation) preterm infants at term-equivalent age to predict 2-year neurodevelopmental outcomes. Using MRI and diffusion MRI on 62 EP and 131 V-LP infants, we built a multimodal feature set for volumetric and structural network analysis. We employed linear and nonlinear machine learning models to predict the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III) scores, assessing predictive accuracy and feature importance. Our findings revealed that models incorporating local connectivity features demonstrated high predictive performance for BSID-III subsets in preterm infants. Specifically, for cognitive scores in preterm (variance explained, 17%) and V-LP infants (variance explained, 17%), and for motor scores in EP infants (variance explained, 15%), models with local connectivity features outperformed others. Additionally, a model using only local connectivity features effectively predicted language scores in preterm infants (variance explained, 15%). This study underscores the value of multimodal feature sets, particularly local connectivity, in predicting neurodevelopmental outcomes, highlighting the utility of machine learning in understanding microstructural changes and their implications for early intervention.

AßPP-tau-HAS1 axis trigger HAS1-related nuclear speckles and gene transcription in Alzheimer's disease.

As the backbone of the extracellular matrix (ECM) and the perineuronal nets (PNNs), hyaluronic acid (HA) provides binding sites for proteoglycans and other ECM components. Although the pivotal of HA has been recognized in Alzheimer's disease (AD), few studies have addressed the relationship between AD pathology and HA synthases (HASs). Here, HASs in different regions of AD brains were screened in transcriptomic database and validated in AßPP/PS1 mice. We found that HAS1 was distributed along the axon and nucleus. Its transcripts were reduced in AD patients and AßPP/PS1 mice. Phosphorylated tau (p-tau) mediates AßPP-induced cytosolic-nuclear translocation of HAS1, and negatively regulated the stability, monoubiquitination, and oligomerization of HAS1, thus reduced the synthesis and release of HA. Furthermore, non-ubiquitinated HAS1 mutant lost its enzyme activity, and translocated from the cytosol into the nucleus, forming nuclear speckles (NS). Unlike the splicing-related NS, less than 1 % of the non-ubiquitinated HAS1 co-localized with SRRM2, proving the regulatory role of HAS1 in gene transcription, indirectly. Thus, differentially expressed genes (DEGs) related to both non-ubiquitinated HAS1 mutant and AD were screened using transcriptomic datasets. Thirty-nine DEGs were identified, with 64.1 % (25/39) showing consistent results in both datasets. Together, we unearthed an important function of the AßPP-p-tau-HAS1 axis in microenvironment remodeling and gene transcription during AD progression, involving the ubiquitin-proteasome, lysosome, and NS systems.

Metal dimer nanojunction-magnetic material composites for magnetic field sensing.

Noble metal nanocrystals are used as high sensitivity optoelectronic sensors, such as surface-enhanced Raman scattering, SERS. The sensing performance of metal nanocrystals can be further improved by forming dimer nanojunctions with strong "plasmonic coupling". Since the strength of "plasmonic coupling" is highly sensitive to the sub-nanoscale spacing between plasmonic nanocrystals in nanojunctions, nanojunctions can be used to detect external stimuli that can change the spacing of nanocrystals in the nanojunction and thus change the sensitivity of the Raman scattering spectrum. Here, we utilize this principle to detect the direction and strength of an external magnetic field (MF) using dimer nanojunctions surrounded by magnetic materials as a sensing platform. The results reveal that the changes in nanocrystal spacing in the nanojunction are caused by the rearrangement of the magnetic material under an external MF, which strongly depends on the interaction between the magnetic material and the ligands on the nanocrystal surface and the steric repulsion generated by the ligand configuration on the nanocrystal surface. Compared with the Raman spectrum without an external MF, the enhancement factors of the Raman scattering spectrum under an external MF can reach up to ∼900%, which makes dimer nanojunctions with magnetic materials suitable for "magnetic field" sensing applications.

Mesenchymal stem cells-based drug delivery systems for diabetic foot ulcer: A review.

The complication of diabetes, which is known as diabetic foot ulcer (DFU), is a significant concern due to its association with high rates of disability and mortality. It not only severely affects patients' quality of life, but also imposes a substantial burden on the healthcare system. In spite of efforts made in clinical practice, treating DFU remains a challenging task. While mesenchymal stem cell (MSC) therapy has been extensively studied in treating DFU, the current efficacy of DFU healing using this method is still inadequate. However, in recent years, several MSCs-based drug delivery systems have emerged, which have shown to increase the efficacy of MSC therapy, especially in treating DFU. This review summarized the application of diverse MSCs-based drug delivery systems in treating DFU and suggested potential prospects for the future research.

Effects of Maternal Dietary Enteromorpha prolifera Polysaccharide Iron Supplement on Mineral Elements and Iron Level of Neonatal Piglets.

Iron plays a key role in maternal health during pregnancy and fetal growth. Enteromorpha polysaccharide-iron (EP-Fe) as an organic iron chelate may improve the iron transmission of mother and offspring, ameliorate the poor pregnancy outcomes of sows, and alleviate the growth restriction of piglets caused by iron deficiency. This study aimed to evaluate the effects of maternal dietary supplementation with EP-Fe on reproductive performance and placental iron transmission of sows, as well as growth performance of piglets. Sixty pregnant sows at the 95th day of gestation were randomly divided into control group and EP-Fe group (EP-Fe, 139 mg kg-1). Blood samples of sows and neonatal piglets, colostrum, and tissue samples were collected on the day of delivery. The animal experiment ended at the 21st day of post-delivery. Results showed that maternal dietary EP-Fe increased colostrum iron (P < 0.05) of sows, as well as final litter weight (P < 0.05) and average daily weight of piglets (P < 0.05) during days 1-21 of lactation, as well as iron and manganese content in umbilical cord blood (P < 0.05) and hepatic iron of neonatal piglets (P < 0.01), and decreased fecal iron (P < 0.001), serum calcium (P < 0.05), phosphorus (P < 0.05), and zinc (P < 0.01) in the parturient sow. RT-qPCR results showed that Fpn1 and Zip14 in placenta, as well as TfR1 and Zip14 in duodenum of neonatal piglets, were activated by maternal EP-Fe supplement. These findings suggest that maternal dietary EP-Fe could increase iron storage of neonatal piglets via improving placental iron transport and iron secretion in colostrum, thus enhancing the growth performance of sucking piglets.

Potential role of microRNA-503 in Icariin-mediated prevention of high glucose-induced endoplasmic reticulum stress.

BACKGROUND: Dysregulated microRNA (miRNA) is crucial in the progression of diabetic nephropathy (DN). AIM: To investigate the potential molecular mechanism of Icariin (ICA) in regulating endoplasmic reticulum (ER) stress-mediated apoptosis in high glucose (HG)-induced primary rat kidney cells (PRKs), with emphasis on the role of miR-503 and sirtuin 4 (SIRT4) in this process. METHODS: Single intraperitoneal injection of streptozotocin (65 mg/kg) in Sprague-Dawley rats induce DN in the in vivo hyperglycemic model. Glucose-treated PRKs were used as an in vitro HG model. An immunofluorescence assay identified isolated PRKs. Cell Counting Kit-8 and flow cytometry analyzed the effect of ICA treatment on cell viability and apoptosis, respectively. Real-time quantitative polymerase chain reaction and western blot analyzed the levels of ER stress-related proteins. Dual luciferase analysis of miR-503 binding to downstream SIRT4 was performed. RESULTS: ICA treatment alleviated the upregulated miR-503 expression in vivo (DN) and in vitro (HG). Mechanistically, ICA reduced HG-induced miR-503 overexpression, thereby counteracting its function in downregulating SIRT4 levels. ICA regulated the miR-503/SIRT4 axis and subsequent ER stress to alleviate HG-induced PRKs injury. CONCLUSION: ICA reduced HG-mediated inhibition of cell viability, promotion of apoptosis, and ER stress in PRKs. These effects involved regulation of the miR-503/SIRT4 axis. These findings indicate the potential of ICA to treat DN, and implicate miR-503 as a viable target for therapeutic interventions in DN.

The Potential of Glucose Treatment to Reduce Reactive Oxygen Species Production and Apoptosis of Inflamed Neural Cells In Vitro.

Neuroinflammation is a key feature in the pathogenesis of entrapment neuropathies. Clinical trial evidence suggests that perineural injection of glucose in water at entrapment sites has therapeutic benefits beyond a mere mechanical effect. We previously demonstrated that 12.5-25 mM glucose restored normal metabolism in human SH-SYFY neuronal cells rendered metabolically inactive from TNF-α exposure, a common initiator of neuroinflammation, and reduced secondary elevation of inflammatory cytokines. In the present study, we measured the effects of glucose treatment on cell survival, ROS activity, gene-related inflammation, and cell cycle regulation in the presence of neurogenic inflammation. We exposed SH-SY5Y cells to 10 ng/mL of TNF-α for 24 h to generate an inflammatory environment, followed by 24 h of exposure to 3.125, 6.25, 12.5, and 25 mM glucose. Glucose exposure, particularly at 12.5 mM, preserved apoptotic SH-SY5Y cell survival following a neuroinflammatory insult. ROS production was substantially reduced, suggesting a ROS scavenging effect. Glucose treatment significantly increased levels of CREB, JNK, and p70S6K (p < 0.01), pointing to antioxidative and anti-inflammatory actions through components of the MAPK family and Akt pathways but appeared underpowered (n = 6) to reach significance for NF-κB, p38, ERK1/2, Akt, and STAT5 (p < 0.05). Cell regulation analysis indicated that glucose treatment recovered/restored function in cells arrested in the S or G2/M-phases. In summary, glucose exposure in vitro restores function in apoptotic nerves after TNF-α exposure via several mechanisms, including ROS scavenging and enhancement of MAPK family and Akt pathways. These findings suggest that glucose injection about entrapped peripheral nerves may have several favorable biochemical actions that enhance neuronal cell function.

Safety and immunogenicity of a modified COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults: an open-labeled, two-centered and multi-arm randomised, phase 1 trial.

BACKGROUND: We assessed the safety and immunogenicity of a core-shell structured lipopolyplex (LPP) based COVID-19 mRNA vaccine, SW-BIC-213, as a heterologous booster in healthy adults. METHODS: We conducted an open-labeled, two-centered, and three-arm randomised phase 1 trial. Healthy adults, who had completed a two-dose of inactivated COVID-19 vaccine for more than six months, were enrolled and randomized to receive a booster dose of COVILO (inactivated vaccine) (n = 20) or SW-BIC-213-25µg (n = 20), or SW-BIC-213-45µg (n = 20). The primary study endpoint was adverse events within 30 days post-boosting. The secondary endpoint was the titers of binding antibodies and neutralizing antibodies against the wild-type (WT) of SARS-CoV-2 as well as variants of concern in serum. The exploratory endpoint was the cellular immune responses. This trial was registered with http://www.chictr.org.cn (ChiCTR2200060355). FINDINGS: Between Jun 6 and Jun 22, 2022, 60 participants were enrolled and randomized to receive a booster dose of SW-BIC-213 (25 µg, n = 20, or 45 µg, n = 20) or COVILO (n = 20). The baseline demographic characteristics of the participants at enrollment were similar among the treatment groups. For the primary outcome, injection site pain and fever were more common in the SW-BIC-213 groups (25 µg and 45 µg). Grade 3 fever was reported in 25% (5/20) of participants in the SW-BIC-213-45µg group but was resolved within 48 h after onset. No fatal events or adverse events leading to study discontinuation were observed. For secondary and exploratory outcomes, SW-BIC-213 elicited higher and longer humoral and cellular immune responses than that in the COVILO group. INTERPRETATION: SW-BIC-213, a core-shell structured lipopolyplex (LPP) based mRNA vaccine, was safe, tolerable, and immunogenic as a heterologous booster in healthy Chinese adults. FUNDING: Shanghai Municipal Government, the Science and Technology and Economic Commission of Shanghai Pudong New Area, and mRNA Innovation and Translation Center of Shanghai.

Dynamics of disease characteristics and viral RNA decay in patients with asymptomatic and mild infections during the Omicron wave in Shanghai, China: A retrospective cohort study.

OBJECTIVES: Asymptomatic infections and mild diseases were more common during the Omicron outbreak in Shanghai, China in 2022. This study aimed to assess the characteristics and viral RNA decay between patients with asymptomatic and mild infections. METHODS: A total of 55,111 patients infected with SARS-CoV-2 who were quarantined in the National Exhibition & Convention Center (Shanghai) Fangcang shelter hospital within 3 days after diagnosis from April 9 to May 23, 2022 were enrolled. The kinetics of cycle threshold (Ct) values of reverse transcription-polymerase chain reaction were assessed. The influencing factors for disease progression and the risk factors for the viral RNA shedding time (VST) were investigated. RESULTS: On admission, 79.6% (43,852/55,111) of the cases were diagnosed with asymptomatic infections, and 20.4% were mild diseases. However, 78.0% of initially asymptomatic subjects developed mild diseases at the follow-up. The final proportion of asymptomatic infections was 17.5%. The median time of symptom onset, the duration of symptoms, and the VST were 2 days, 5 days, and 7 days, respectively. Female, age 19-40 years, underlying comorbidities with hypertension and diabetes, and vaccination were associated with higher risks of progressing to mildly symptomatic infections. In addition, mildly symptomatic infections were found to be associated with prolonged VST compared with asymptomatic infections. However, the kinetics of viral RNA decay and dynamics of Ct values were similar among asymptomatic subjects, patients with asymptomatic-to-mild infection, and patients with mild infection. CONCLUSION: A large proportion of initially diagnosed asymptomatic Omicron infections is in the presymptomatic stage. The Omicron infection has a much shorter incubation period and VST than previous variants. The infectivity of asymptomatic infections and mildly symptomatic infections with Omicron is similar.

Antiphospholipid antibodies in chronic thromboembolic pulmonary hypertension.

Acquired thrombophilia and in particular the presence of antiphospholipid antibodies (aPL) may play an important role in the development of chronic thromboembolic pulmonary hypertension (CTEPH). Young patients suffering from an episode of unprovoked pulmonary embolism (PE), or PE provoked by mild risk factors, should be tested for aPL. In case of a positive result, they should be closely followed up and lifelong anticoagulant treatment should be considered. Indeed, aPL-induced thrombophilia may favor PE recurrence with the consequence of possible CTEPH development. The aPL profiles play an important role in this pathway. Patients with PE and triple positivity (lupus anticoagulant, LAC, anti-cardiolipin, aCL, and anti-ß2-glycoprotein I, aß2GPI) are at the highest risk of recurrence and deserve maximum protection by anticoagulant treatment with warfarin.

Pharmacokinetics, mass balance, and metabolism of [14C]TPN171, a novel PDE5 inhibitor, in humans for the treatment of pulmonary arterial hypertension.

TPN171 is a novel phosphodiesterase-5 (PDE5) inhibitor used to treat pulmonary arterial hypertension (PAH) and erectile dysfunction (ED), which currently is undergoing phase II clinical trials in China. In this single-center, single-dose, nonrandomized, and open design study, radiolabeled [14C]TPN171 was used to investigate the metabolic mechanism, pharmacokinetic characteristics, and clearance pathways of TPN171 in 6 healthy Chinese male volunteers. Each volunteer was administered a single oral suspension of 10 mg (100 µCi) of [14C]TPN171. We found that TPN171 was absorbed rapidly in humans with a peak time (Tmax) of 0.667 h and a half-life (t1/2) of approximately 9.89 h in plasma. Excretion of radiopharmaceutical-related components was collected 216 h after administration, accounting for 95.21% of the dose (46.61% in urine and 48.60% in feces). TPN171 underwent extensive metabolism in humans. Twenty-two metabolites were detected in human plasma, urine, and feces using a radioactive detector combined with a high-resolution mass spectrometer. According to radiochromatograms, a glucuronide metabolite of O-dealkylated TPN171 exceeded 10% of the total drug-related components in human plasma. However, according to the Food and Drug Administration (FDA) guidelines, no further tests are needed to evaluate the safety of this metabolite because it is a phase II metabolite, but the compound is still worthy of attention. The main metabolic biotransformation of TPN171 was mono-oxidation (hydroxylation and N-oxidation), dehydrogenation, N-dealkylation, O-dealkylation, amide hydrolysis, glucuronidation, and acetylation. Cytochrome P450 3A4 (CYP3A4) mainly catalyzed the formation of metabolites, and CYP2E1 and CYP2D6 were involved in the oxidative metabolism of TPN171 to a lesser extent. According to the incubation data, M1 was mainly metabolized to M1G by UDP-glucuronosyltransferase 1A9 (UGT1A9), followed by UGT1A7 and UGT1A10.

Impact of dietary supplementation with N-carbamoyl-aspartic acid on serum metabolites and intestinal microflora of sows.

BACKGROUND: N-Carbamoyl-aspartic acid (NCA) is a critical precursor for de novo biosynthesis of pyrimidine nucleotides. To investigate the cumulative effects of maternal supplementation with NCA on the productive performance, serum metabolites and intestinal microbiota of sows, 40 pregnant sows (∼day 80) were assigned into two groups: (1) the control (CON) and (2) treatment (NCA, 50 g t-1 NCA). RESULTS: Results showed that piglets from the NCA group had heavier birth weight than those in the CON group (P < 0.05). In addition, maternal supplementation with NCA decreased the backfat loss of sows during lactation (P < 0.05). Furthermore,16S-rRNA sequencing results revealed that maternal NCA supplementation decreased the abundance of Cellulosilyticum, Fournierella, Anaerovibrio, and Oribacterium genera of sows during late pregnancy (P < 0.05). Similarly, on the 14th day of lactation, maternal supplementation with NCA reduced the diversity of fecal microbes of sows as evidenced by significantly lower observed species, Chao1, and Ace indexes, and decreased the abundance of Lachnospire, Faecalibacterium, and Anaerovorax genera, while enriched the abundance of Catenisphaera (P < 0.05). Untargeted metabolomics showed that a total of 48 differentially abundant biomarkers were identified, which were mainly involved in metabolic pathways of arginine/proline metabolism, phenylalanine/tyrosine metabolism, and fatty acid biosynthesis, etc. CONCLUSION: Overall, the results indicated that NCA supplementation regulated intestinal microbial composition of sows and serum differential metabolites related to arginine, proline, phenylalanine, tyrosine, and fatty acids metabolism that may contribute to regulating the backfat loss of sows, and the birth weight and diarrhea rate of piglets. © 2022 Society of Chemical Industry.

Clinical experience of REcanalisation and balloon-oriented puncture for Re-insertion of long- term dialysis catheter in nonpatent central veins / 中华肝脏病杂志

It is difficult to insert long-term dialysis catheters after severe stenosis or occlusion of the internal jugular vein and innominate vein. We used REcanalisation and balloon-oriented puncture for Re-insertion of dialysis catheter in nonpatent central veins (REBORN) in seven patients with severe central venous lesions, and all patients were inserted with long-term dialysis catheters successfully. None had severe complications such as pneumothorax, hemothorax, or pulmonary embolism during operation. All catheters functioned well after postoperative follow-up of 2 months. REBORN provides a novel approach to establish difficult dialysis pathways.

Morphological classification and clinical significance of the coracoid process based on CT three-dimensional reconstruction / 解剖学报

Objective To provide anatomical basis for clinical treatment of acromioclavicular joint dislocation by studying the morphology of coracoid process of human scapula. Methods A total of 500 patients with shoulder injury were selected from the Affiliated Hospital of Traditional Chinese Medicine of Southwest Medical University in Sichuan Province, and 300 patients were selected as subjects, including 159 cases of right shoulder and 141 cases of left shoulder. CT scan images and 3D reconstruction results of scapula of the subjects were collected. The basic morphological characteristics of coracoid process CT images of the subjects were observed, and the relevant parameters were measured, including the longest horizontal distance of the coracoid process tip and the thickness of the midpoint (cd, pp’), the distance from the upper part of the coracoid process scapula to the base and the thickness of the midpoint (mn, kk’). The distance from the apex of the coracoid process to the base of the coracoid process (ab), the longest horizontal distance of the recursion part of the coracoid process (ef), the distance of as (point s was the intersection of point a perpendicular to mn), the distance of hj (point h and j were the intersection of the base of the coracoid process and the recursion part respectively), and ik (point i was the intersection of point k perpendicular to mn and the coracoid process retraction). Results According to the morphological characteristics of coracoid process, they were divided into five types, including peanut 29. 7%; Short rod type accounted for 27. 4%; Melon seed type accounted for 12. 6%; Rod type accounted for 17. 0%; Wedge type accounted for 13. 3%. Through data comparison, it was found that the distance ef and distance hj on the left were larger than those on the right, P<0. 05. All types had statistical difference in comparison distance cd, P<0. 05. The melon seed type showed statistical differences with peanut type, wedge type, long stick type and short stick type in thickness pp’, distance ab and as of point p, P<0. 05. In the comparison of point K thickness kk’, there was statistical difference between melon seed type and other four types, P<0. 05. In the distance ab comparison, there was statistical difference between the short bar type and the other four types, P < 0. 05. Conclusion The study on the morphology of coracoid process can provide anatomical basis for clinical reconstruction of coracoid ligament to treat acromioclavicular joint dislocation.

A survey of clinical and laboratory characteristics of the dengue fever epidemic from 2017 to 2019 in Zhejiang, China.

To explore the epidemic, clinical, and laboratory characteristics of dengue patients in Zhejiang and the possible mechanism. Epidemic, clinical and laboratory data of 231 dengue patients admitted to the Second Affiliated Hospital of Zhejiang Traditional Chinese Medicine University between August 2017 and December 2019 were collected. GSE43777 dataset was downloaded from the Gene Expression Omnibus database and was used for the immune cell infiltration analysis, logistic regression analysis, and nomogram construction. Gene set enrichment analysis (GSEA) was performed to explore the possible regulatory pathways in dengue infection. Further, the receiver operating characteristic curve analysis and decision curve analysis were conducted to evaluate the value of related immune cells in predicting dengue severity. Among the 231 patients, the gender ratio was 1:1.1 (male/female). The patients in the <60 years age group, 60 to 80 years age group, and >80 years age group were 47.2%, 45.5%, and 7.3%, respectively. The major symptoms were fever (100%), weak (98.3%), anorexia (76.6%), muscle and joint pain (62.3%), and nausea (46.8%). In dengue patients, 98.7% of serum samples had decreased platelet levels, 96.5% of them had decreased white blood cell (WBC) levels, 97.8% had elevated aspartate aminotransferase levels, 82.3% had elevated lactate dehydrogenase levels, 49.4% had increased creatinine levels, and 35.5% had increased creatine kinase levels. Pneumonia, pleural effusion, and bilateral pleural reaction were observed in 16.5%, 8.2%, and 4.8%, respectively of dengue patients. Gallbladder wall roughness and splenomegaly accounted for 6.1% and 4.3% of all cases. Moreover, the levels of T cell, B cell, and dendritic cells were significantly higher in the convalescent group and they were involved in immune- and metabolism-related pathways. Of note, low levels of these 3 immune cells correlated with high dengue infection risk, while only dendritic cells exhibited satisfactory performance in predicting dengue severity. Dengue fever patients often onset with fever, accompanied by mild abnormalities of the blood system and other organ functions. Moreover, T cells, B cells, and dendritic cells might be involved in dengue infection and development.

Maternal pyrimidine nucleoside supplementation regulates fatty acid, amino acid and glucose metabolism of neonatal piglets.

Pyrimidine nucleosides (PN) are abundant in mammalian milk and mainly involved in glycogen deposition and lipid metabolism. To investigate the effects of maternal supplementation with pyrimidine nucleoside on glucose, fatty acids (FAs), and amino acids (AAs) metabolism in neonatal piglets. Forty pregnant sows were randomly assigned into the control (CON) group (fed a basal diet, n = 20) or the PN group (fed a basal diet supplemented with PN at 150 g/t, n = 20). Litter size, born alive and birth litter weight were recorded. The serum and placenta of sows, and jejunum and liver of neonatal piglets were sampled. The results indicated that supplementing sow diets with PN decreased birth mortality and increased the birth weight of piglets (P < 0.05). In addition, neonates from sows supplemented with PN had higher glucose levels in serum and liver compared with the CON group (P < 0.05). Moreover, maternal PN supplementation regulated the ratio of saturated FAs and polyunsaturated FAs, and AAs content in serum and liver of piglets (P < 0.05). Furthermore, an up-regulation of mRNA expression of genes related to glucose and AA transport were observed in the neonatal jejunum from the PN group (P < 0.05). Additionally, hepatic protein expressions of phosphorylated hormone-sensitive lipase (P-HSL), HSL, sterol regulatory element-binding transcription factor 1c (SREBP-1c), and phosphorylated protein kinase B (P-AKT) was higher in the piglets from the PN group than the CON group (P < 0.05). Together, maternal PN supplementation may regulate nutrient metabolism of neonatal piglets by modulating the gene expression of glucose and AA transporters in placenta and jejunum, and the gene and protein expression of key enzymes related to lipid metabolism in liver of neonatal piglets, which may improve the reproductive performance of sows.

Formation of Fluorovinyl Spiro-[imidazole-indene] and α-Amino-ß-naphthalenones via Rh(III)-Catalyzed Cascade C-H Functionalization.

An efficacious method for building fluorovinyl spiro-[imidazole-indene] and α-amino-ß-naphthalenone skeletons synchronously has been shown to consist of Rh(III)-catalyzed C-H functionalization between 2H-imidazoles and difluoromethylene alkynes. This protocol demonstrates a practical and straightforward route for installing fluorine elements in the envisioned position of heterocyclic compounds.

Hemostasis and Anti-Inflammatory Abilities of AuNPs-Coated Chitosan Dressing for Burn Wounds.

Burn injuries are a common hazard in the military, as fire is likely to be weaponized. Thus, it is important to find an effective substance to accelerate burn wound healing. This study used chitosan and gold nanoparticles (AuNPs) as wound dressings and investigated their effectiveness in femoral artery hemorrhage swine and rat burn models. Chitosan dressing has significant hemostatic properties compared with gauze. Histological results showed that burn wounds treated with chitosan or AuNP-coated chitosan dressings exhibited more cells and a continuous structure of the epidermis and dermis than those of the control and untreated lesion groups. Furthermore, both chitosan dressings have been shown to positively regulate the expression of genes- and cytokines/chemokines-related to the wound healing process; AuNP-coated chitosan significantly lessened severe sepsis and inflammation, balanced the activities of pro-fibrotic and anti-fibrotic ligands for tissue homeostasis, regulated angiogenesis, and inhibited apoptosis activity, thereby being beneficial for the burn microenvironment. Hence, chitosan alone or in combination with AuNPs represents a prospective therapeutic substance as a burn dressing which might be helpful for burn wound care. This study provides a novel hemostasis dressing for modern warfare that is simple to use by most medical and paramedical personnel handling for burn treatment.

Safety, tolerability, and pharmacokinetics of VV116, an oral nucleoside analog against SARS-CoV-2, in Chinese healthy subjects.

VV116 (JT001) is an oral drug candidate of nucleoside analog against SARS-CoV-2. The purpose of the three phase I studies was to evaluate the safety, tolerability, and pharmacokinetics of single and multiple ascending oral doses of VV116 in healthy subjects, as well as the effect of food on the pharmacokinetics and safety of VV116. Three studies were launched sequentially: Study 1 (single ascending-dose study, SAD), Study 2 (multiple ascending-dose study, MAD), and Study 3 (food-effect study, FE). A total of 86 healthy subjects were enrolled in the studies. VV116 tablets or placebo were administered per protocol requirements. Blood samples were collected at the scheduled time points for pharmacokinetic analysis. 116-N1, the metabolite of VV116, was detected in plasma and calculated for the PK parameters. In SAD, AUC and Cmax increased in an approximately dose-proportional manner in the dose range of 25-800 mg. T1/2 was within 4.80-6.95 h. In MAD, the accumulation ratio for Cmax and AUC indicated a slight accumulation upon repeated dosing of VV116. In FE, the standard meal had no effect on Cmax and AUC of VV116. No serious adverse event occurred in the studies, and no subject withdrew from the studies due to adverse events. Thus, VV116 exhibited satisfactory safety and tolerability in healthy subjects, which supports the continued investigation of VV116 in patients with COVID-19.