Physical therapy and non-surgical manual disc reduction combined with anterior repositioning splint for acute disc displacement without reduction of the temporomandibular joint in adolescents.

OBJECTIVES: Current studies on the treatment of adolescent patients with disc displacement without reduction (DDWOR) are limited by short follow-up periods and small sample sizes, and there are few comparative studies on the efficacy of conservative treatment with and without disc reduction for acute DDWOR. This study compared the therapeutic effects of two conservative treatment methods: physical therapy alone and physical therapy combined with non-surgical manual disc reduction and anterior repositioning splints (ARS), in adolescent patients with acute DDWOR. MATERIALS AND METHODS: This retrospective study included adolescent patients with DDWOR who underwent physical therapy at the Temporomandibular Joint Rehabilitation Department of the Shanghai Ninth People's Hospital from January 2018 to December 2021. Patient assessment data were collected before and after treatment. Patients were followed up through telephone and online questionnaires from March to August 2023. RESULTS: The results indicate that compared to physical therapy alone, the combination of physical therapy and non-surgical manual disc reduction with ARS showed better short-term efficacy, improved mouth opening, and better long-term pain control. Also, it may be effective in preventing degenerative joint disease. CONCLUSIONS: This combination therapy is recommended for clinical application in adolescent patients with acute DDWOR. CLINICAL RELEVANCE: The present research demonstrates the superior efficacy of physical therapy and non-surgical manual disc reduction combined with anterior repositioning splint in adolescent patients with acute DDWOR.

Long-Term Prognosis and Influencing Factors of Chinese Adolescents With Temporomandibular Disorder After Physical Therapy.

BACKGROUND: Physical therapy is the preferred conservative treatment for patients with temporomandibular disorder (TMD). However, few studies have investigated the application of physical therapy in adolescents, especially follow-up studies on the long-term prognosis of these patients. This study investigated the short-term effects and long-term prognosis of physical therapy in adolescent patients with TMD and the factors influencing long-term symptoms. METHODS: Information regarding baseline data, specific treatment methods, treatment times and evaluation results was collected retrospectively for adolescent patients with TMD who received physical therapy. Patients were followed up via telephone and online questionnaires, and the influence of age, sex, disease course, mouth opening, pain intensity, oral parafunctional habits and treatment methods on long-term symptoms was analysed. RESULTS: Pain intensity, maximum mouth opening and the joint noise score improved significantly in 270/286 patients who received individualised comprehensive physical therapy. TMD-related symptoms improved with no noticeable impact on daily life in 187/199 patients who were followed up for an extended period (average, 30.71 ± 10.86 months) and were divided into asymptomatic or symptomatic groups according to the persistence of symptoms. Logistic regression analysis revealed that uncorrected oral parafunctional habits and fewer treatments were related to long-term symptoms. CONCLUSION: The long-term prognosis of adolescent patients with TMD after physical therapy was satisfactory. However, 52.8% of the patients experienced persistent TMD-related symptoms for an extended period, possibly due to insufficient treatment times and parafunctional habits. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT05781607.

Analysis of the thermal insulation performance of cement with waste glass powder in geothermal well.

To improve the heat extraction efficiency from the wellbore fluids to the stratum in the geothermal well, thermal insulation cement, which contains of waste glass powder as a heat-insulating material, is proposed to apply in geothermal well's middle and upper sections in the paper. Effect of such glass powers on mechanic and thermal property of thermal insulation cement was then investigated. Various tests were carried out to measure compressive strength, thermal conductivity, microstructure porosity etc. parameters of the thermal insulation cement. Results showed that the waste glass powder would enhance its the compressive strength and improve its the thermal insulation performance. Correlation study between contents of the added waste glass powder in geothermal cements and its mechanic and thermal property was conducted. It was found that thermal insulation cement exhibited its optimum performance when the added content of glass powers was 20% in weight. Analysis of the microstructure porosity with SEM found that the pores in thermal insulation cement with added waste glass powders were mostly closed, tiny and even, and therefore contributed to the compressive strength of the thermal insulation cement; such pores would be also beneficial to improving its thermal insulation performance.

Effect of volatile versus propofol anaesthesia on major complications and mortality after cardiac surgery: a multicentre randomised trial.

BACKGROUND: The comparative effectiveness of volatile anaesthesia and total intravenous anaesthesia (TIVA) in terms of patient outcomes after cardiac surgery remains a topic of debate. METHODS: Multicentre randomised trial in 16 tertiary hospitals in China. Adult patients undergoing elective cardiac surgery were randomised in a 1:1 ratio to receive volatile anaesthesia (sevoflurane or desflurane) or propofol-based TIVA. The primary outcome was a composite of predefined major complications during hospitalisation and mortality 30 days after surgery. RESULTS: Of the 3123 randomised patients, 3083 (98.7%; mean age 55 yr; 1419 [46.0%] women) were included in the modified intention-to-treat analysis. The composite primary outcome was met by a similar number of patients in both groups (volatile group: 517 of 1531 (33.8%) patients vs TIVA group: 515 of 1552 (33.2%) patients; relative risk 1.02 [0.92-1.12]; P=0.76; adjusted odds ratio 1.05 [0.90-1.22]; P=0.57). Secondary outcomes including 6-month and 1-yr mortality, duration of mechanical ventilation, length of ICU and hospital stay, and healthcare costs, were also similar for the two groups. CONCLUSIONS: Among adults undergoing cardiac surgery, we found no difference in the clinical effectiveness of volatile anaesthesia and propofol-based TIVA. CLINICAL TRIAL REGISTRATION: Chinese Clinical Trial Registry (ChiCTR-IOR-17013578).

Advances in regenerative rehabilitation in the rehabilitation of musculoskeletal injuries.

In the rapidly advancing field of regenerative medicine, relying solely on cell transplantation alone may be insufficient for achieving functional recovery, and rehabilitation before and after transplantation is crucial. Regenerative rehabilitation functions by synergizing the therapeutic effects of regeneration and rehabilitation to maximize tissue regeneration and patient function. We used the keywords "regenerative rehabilitation" to search across the database for published works; this review discusses the development of regenerative rehabilitation for the treatment of musculoskeletal injuries. Rehabilitation has become a crucial component of regenerative medicine because it can enhance patients' functional activity and facilitate their early return to society. Experimental data increasingly demonstrates that rehabilitation interventions support the regeneration of transplanted tissues.

Regenerative medicine concepts can be incorporated into rehabilitation to help patients achieve a better functional recovery outcome. Rehabilitation therapy can help patients return to society sooner following an injury. Regenerative medicine concepts can also be integrated into regenerative therapy to maximize its benefits when compared with traditional rehabilitation or regenerative therapy alone. The development of regenerative rehabilitation for the treatment of skeletal muscle, bone and bone junction injuries is reviewed in this article.

Computation-Guided Rational Design of Cysteine-Less Protein Variants in Engineered hCGL.

The engineered human cystathionine-γ-lyase (hCGL) resulting in enhanced activity toward both cysteine and cystine unveils a potential robust antitumor activity. However, the presence of cysteine residues has the potential to induce oligomerization or incorrect disulfide bonding, which may decrease the bioavailability of biopharmaceuticals. Through a meticulous design process targeting the cysteine residues within engineered hCGL, a set of potential beneficial mutants were obtained by virtual screening employing Rosetta and ABACUS. Experimental measurements have revealed that most of the mutants showed increased activity toward both substrates l-Cys and CSSC. Furthermore, mutants C109V and C229D demonstrated Tm value increases of 8.2 and 1.8 °C, respectively. After an 80 min incubation at 60 °C, mutant C229D still maintained high residual activity. Unexpectedly, mutant C109V, displaying activity approximately 2-fold higher than the activity of wild type (WT) for both substrates, showed disappointing instability in plasma, which suggests that computational design still requires further consideration. Analysis of their structure and molecular dynamics (MD) simulation revealed the impact of hydrophobic interaction, hydrogen bonds, and near-attack conformation (NAC) stability on activity and stability. This study acquired information about mutants that exhibit enhanced activity or thermal resistance and serve as valuable guidance for subsequent specific cysteine modifications.

Targeting optimal power consumption: Optimizing operational parameters for orchard furrowing and fertilizing machine.

In response to the problem of excessive power consumption during the furrowing operation of orchard furrowing fertilizer machines, an optimization experiment of furrowing operation parameters for orchard furrowing fertilizer machine was conducted based on discrete element simulations. This research focused on the impact of furrowing device operation parameters on furrowing power consumption under full machine operating conditions. Firstly, a kinematics analysis of the soil granules during cutting was done. The mathematical model of soil granules through three movement processes of rising, detachment, and falling was established to determine the main factors affecting the power consumption of furrowing. Secondly, in assessing the furrowing power consumption, the stability coefficient of the furrowing depth, and the percentage of soil cover, alongside the key parameters of furrowing depth, forward propulsion velocity, and furrowing blade rotation speed, a comprehensive quadratic orthogonal rotation regression experiment was meticulously conducted. It was established that test metrics and test parameters regress. Finally, the test parameters were comprehensively optimized after analyzing each factor's impact on the test metrics. The orchard furrowing fertilizer machine's optimal operating parameters were determined, and the verification test was performed. According to the field test findings, the forward propulsion velocity was 785 m/h, and the furrowing blade rotation speed was 190 r/min when the furrowing depth was 275 mm. At this point, the furrowing power consumption was 2.39 kW, the soil cover percentage was 69.06%, and the furrowing depth stability coefficient was 95.08%. These results were in line with the requirements of orchard furrowing operation. The findings of the study can be utilized as a guide for structural changes to orchard furrowing equipment and the management of furrowing operation parameters.

Ubiquitin-specific proteinase 1 stabilizes PRRSV nonstructural protein Nsp1ß to promote viral replication by regulating K48 ubiquitination.

The porcine reproductive and respiratory syndrome virus (PRRSV) can lead to severe reproductive problems in sows, pneumonia in weaned piglets, and increased mortality, significantly negatively impacting the economy. Post-translational changes are essential for the host-dependent replication and long-term infection of PRRSV. Uncertainty surrounds the function of the ubiquitin network in PRRSV infection. Here, we screened 10 deubiquitinating enzyme inhibitors and found that the ubiquitin-specific proteinase 1 (USP1) inhibitor ML323 significantly inhibited PRRSV replication in vitro. Importantly, we found that USP1 interacts with nonstructural protein 1ß (Nsp1ß) and deubiquitinates its K48 to increase protein stability, thereby improving PRRSV replication and viral titer. Among them, lysine at position 45 is essential for Nsp1ß protein stability. In addition, deficiency of USP1 significantly reduced viral replication. Moreover, ML323 loses antagonism to PRRSV rSD16-K45R. This study reveals the mechanism by which PRRSV recruits the host factor USP1 to promote viral replication, providing a new target for PRRSV defense.IMPORTANCEDeubiquitinating enzymes are critical factors in regulating host innate immunity. The porcine reproductive and respiratory syndrome virus (PRRSV) nonstructural protein 1ß (Nsp1ß) is essential for producing viral subgenomic mRNA and controlling the host immune system. The host inhibits PRRSV proliferation by ubiquitinating Nsp1ß, and conversely, PRRSV recruits the host protein ubiquitin-specific proteinase 1 (USP1) to remove this restriction. Our results demonstrate the binding of USP1 to Nsp1ß, revealing a balance of antagonism between PRRSV and the host. Our research identifies a brand-new PRRSV escape mechanism from the immune response.

Computational design of α-amylase from Bacillus licheniformis to increase its activity and stability at high temperatures.

The thermostable α-amylase derived from Bacillus licheniformis (BLA) has multiple advantages, including enhancing the mass transfer rate and by reducing microbial contamination in starch hydrolysis. Nonetheless, the application of BLA is constrained by the accessibility and stability of enzymes capable of achieving high conversion rates at elevated temperatures. Moreover, the thermotolerance of BLA requires further enhancement. Here, we developed a computational strategy for constructing small and smart mutant libraries to identify variants with enhanced thermostability. Initially, molecular dynamics (MD) simulations were employed to identify the regions with high flexibility. Subsequently, FoldX, a computational design predictor, was used to design mutants by rigidifying highly flexible residues, whereas the simultaneous decrease in folding free energy assisted in improving thermostability. Through the utilization of MD and FoldX, residues K251, T277, N278, K319, and E336, situated at a distance of 5 Å from the catalytic triad, were chosen for mutation. Seventeen mutants were identified and characterized by evaluating enzymatic characteristics and kinetic parameters. The catalytic efficiency of the E271L/N278K mutant reached 184.1 g L-1 s-1, which is 1.88-fold larger than the corresponding value determined for the WT. Furthermore, the most thermostable mutant, E336S, exhibited a 1.43-fold improvement in half-life at 95 â„ƒ, compared with that of the WT. This study, by combining computational simulation with experimental verification, establishes that potential sites can be computationally predicted to increase the activity and stability of BLA and thus provide a possible strategy by which to guide protein design.

Roles of the N-terminal motif in improving the activity and soluble expression of phenylalanine ammonia lyases in Escherichia coli.

Phenylalanine ammonia-lyase (PAL) has various applications in fine chemical manufacturing and the pharmaceutical industry. In particular, PAL derived from Anabaena variabilis (AvPAL) is used as a therapeutic agent to the treat phenylketonuria in clinical settings. In this study, we aligned the amino acid sequences of AvPAL and PAL derived from Nostoc punctiforme (NpPAL) to obtain several mutants with enhanced activity, expression yield, and thermal stability via amino acid substitution and saturation mutagenesis at the N-terminal position. Enzyme kinetic experiments revealed that the kcat values of NpPAL-N2K, NpPAL-I3T, and NpPAL-T4L mutants were increased to 3.2-, 2.8-, and 3.3-fold that of the wild-type, respectively. Saturation mutagenesis of the fourth amino acid in AvPAL revealed that the kcat values of AvPAL-L4N, AvPAL-L4P, AvPAL-L4Q and AvPAL-L4S increased to 4.0-, 3.7-, 3.6-, and 3.2-fold, respectively. Additionally, the soluble protein yield of AvPAL-L4K increased to approximately 14 mg/L, which is approximately 3.5-fold that of AvPAL. Molecular dynamics studies further revealed that maintaining the attacking state of the reaction and N-terminal structure increased the rate of catalytic reaction and improved the solubility of proteins. These findings provide new insights for the rational design of PAL in the future.

IGF2BP3-mediated enhanced stability of MYLK represses MSC adipogenesis and alleviates obesity and insulin resistance in HFD mice.

Mesenchymal stem cells (MSCs) hold immense potential as multipotent stem cells and serve as a primary source of adipocytes. The process of MSC adipogenesis plays a crucial role in maintaining systemic metabolic homeostasis and has garnered significant attention in tissue bioengineering. N6-methyladenosine (m6A), the most prevalent RNA modification, is known to regulate cell fate and disease. However, the precise involvement of m6A readers in MSC adipogenesis remains unclear. In this study, we investigated the impact of IGF2BP3, a prominent m6A reader, on MSC adipogenesis. Our findings revealed a decrease in IGF2BP3 expression during the natural adipogenic differentiation of MSCs. Furthermore, IGF2BP3 was found to repress MSC adipogenesis by augmenting the levels of MYLK, a calcium/calmodulin-dependent kinase. Mechanistically, IGF2BP3 interacted with MYLK mRNA in an m6A-dependent manner, extending its half-life and subsequently inhibiting the phosphorylation of the ERK1/2 pathway, thereby impeding the adipogenic differentiation of MSCs. Additionally, we successfully achieved the overexpression of IGF2BP3 through intraperitoneal injection of adeno-associated virus serotype Rec2, which specifically targeted adipose tissue. This intervention resulted in reduced body weight and improved insulin resistance in high-fat diet mice. Overall, our study provides novel insights into the role of IGF2BP3 in MSC adipogenesis, shedding light on adipocyte-related disorders and presenting potential targets for related biomedical applications.

Total Synthesis of Nikkomycin Sz and Nikkomycin Soz.

The nikkomycins Sz/Soz are a class of locked nucleoside antibiotics that share a common [5,6] trans-bicyclic core. Herein we present an efficient synthesis of these nikkomycins from diene, using neighboring group participation N-glycosylation and stereoselective oxidation state installation. This synthetic strategy overcomes several challenges due to the poor redox tolerance of the uracil base, the high strain of the trans-fused furanopyran C8 monosaccharides, and the acid-sensitive glycosidic bond when dealing with the deoxynucleotide natural product nikkomycin Sz.

Unbiased multitissue transcriptomic analysis reveals complex neuroendocrine regulatory networks mediated by spinal cord injury-induced immunodeficiency.

BACKGROUND: Spinal cord injury (SCI), which causes loss of sensory and motor function in the body below the level of injury, is a devastating disease of the central nervous system. SCI leads to severe secondary immunosuppression, called SCI-induced immunodeficiency syndrome (SCI-IDS), which is characterized by increased susceptibility to infection and further exacerbates neurological dysfunction. Several studies have suggested that SCI-IDS is an independent risk factor for poor neurological prognosis. SCI-IDS predominantly occurs following injury above the T5 levels and eventually leads to systemic immune failure, possibly via the sympathetic-adrenal medullary axis and the hypothalamic‒pituitary‒adrenal (HPA) axis. However, the mechanism remains unclear. METHODS AND OBJECTIVES: The concentrations of adrenocorticotropic hormone and cortisol in plasma, as well as changes in sympathetic activity (blood pressure and catecholamine levels in plasma), were assessed in rats in the high-level (T3) spinal cord injury (T3-SCI) group and the low-level (T10) spinal cord injury (T10-SCI) group. Second, the differential regulation of the gene network between the sympathetic-adrenal medullary axis and the HPA axis was explored by histology and multitissue transcriptomics, and the neuroendocrine-immune network associated with SCI-IDS was further elucidated. RESULTS: The spleen and thymus gland, which are secondary immune organs, were significantly atrophied in rats in the T3-SCI group, and the white pulp of the spleen was significantly atrophied. The level of cortisol, which is mediated by the adrenal glands, was markedly elevated, but norepinephrine levels were markedly decreased. There was no difference in adrenocorticotropic hormone expression between any of the groups. The transcriptome analysis results showed that the downregulated differentially expressed genes (DEGs) in the T3-SCI group were enriched in the GO term immunoregulation, indicating that splenic immune function was markedly impaired after high-level SCI. The upregulated DEGs in the hypothalamus (hub genes: Nod2, Serpine1, Cebpb, Nfkbil1, Ripk2, Zfp36, Traf6, Akap8, Gfer, Cxcl10, Tnfaip3, Icam1, Fcgr2b, Ager, Dusp10, and Mapkapk2) were significantly enriched in inflammatory pathways, and the downregulated genes (hub genes: Grm4, Nmu, P2ry12, rt1-bb1, Oprm1, Zfhx2, Gpr83, and Chrm2) were enriched in pathways related to inhibitory Gi-mediated G protein-coupled receptor (Gi-GPCR) neurons and neuropeptide changes. The upregulated genes in the adrenal glands (hub genes: Ciart, per2, per3, cry1, and cry2) were enriched in cortisol secretion and circadian rhythm changes, and the downregulated genes (hub genes: IL7r, rt1-bb, rt1-bb1, rt1-da, rt1-ba, cd74, cxcr3, vcam1, ccl5, bin1, and IL8) were significantly enriched in MHC-mediated immune responses. CONCLUSIONS: To explore the possible mechanism underlying SCI-IDS, this study assessed the differential regulation of the gene network associated with neuroendocrine immunity after SCI. Progressive neuroinflammation spreads after injury, and neurotransmission through Gi-mediated G protein-coupled receptors in the HPA axis and neuropeptide production by the hypothalamus are inhibited. Disruption of the connection between the hypothalamus and the adrenal glands causes autonomous regulation of the adrenal glands, disturbance of circadian rhythm and finally hypercortisolemia, leading to general suppression of peripheral adaptive immunity. Neuraxial nerve inflammation caused by SCI persists indefinitely, blocking nerve repair; persistent system-wide immunosuppression in the periphery results in increased susceptibility to infection, leading to poor neurological prognosis.

The African swine fever virus I10L protein inhibits the NF-κB signaling pathway by targeting IKKß.

Proinflammatory factors play important roles in the pathogenesis of African swine fever virus (ASFV), which is the causative agent of African swine fever (ASF), a highly contagious and severe hemorrhagic disease. Efforts in the prevention and treatment of ASF have been severely hindered by knowledge gaps in viral proteins responsible for modulating host antiviral responses. In this study, we identified the I10L protein (pI10L) of ASFV as a potential inhibitor of the TNF-α- and IL-1ß-triggered NF-κB signaling pathway, the most canonical and important part of host inflammatory responses. The ectopically expressed pI10L remarkably suppressed the activation of NF-κB signaling in HEK293T and PK-15 cells. The ASFV mutant lacking the I10L gene (ASFVΔI10L) induced higher levels of proinflammatory cytokines production in primary porcine alveolar macrophages (PAMs) compared with its parental ASFV HLJ/2018 strain (ASFVWT). Mechanistic studies suggest that pI10L inhibits IKKß phosphorylation by reducing the K63-linked ubiquitination of NEMO, which is necessary for the activation of IKKß. Morever, pI10L interacts with the kinase domain of IKKß through its N-terminus, and consequently blocks the association of IKKß with its substrates IκBα and p65, leading to reduced phosphorylation. In addition, the nuclear translocation efficiency of p65 was also altered by pI10L. Further biochemical evidence supported that the amino acids 1-102 on pI10L were essential for the pI10L-mediated suppression of the NF-κB signaling pathway. The present study clarifies the immunosuppressive activity of pI10L, and provides novel insights into the understanding of ASFV pathobiology and the development of vaccines against ASF. IMPORTANCE African swine fever (ASF), caused by the African swine fever virus (ASFV), is now widespread in many countries and severely affects the commercial rearing of swine. To date, few safe and effective vaccines or antiviral strategies have been marketed due to large gaps in knowledge regarding ASFV pathobiology and immune evasion mechanisms. In this study, we deciphered the important role of the ASFV-encoded I10L protein in the TNF-α-/IL-1ß-triggered NF-κB signaling pathway. This study provides novel insights into the pathogenesis of ASFV and thus contributes to the development of vaccines against ASF.

Novel insights into STAT3 in renal diseases.

Signal transducer and activator of transcription 3 (STAT3) is a cell-signal transcription factor that has attracted considerable attention in recent years. The stimulation of cytokines and growth factors can result in the transcription of a wide range of genes that are crucial for several cellular biological processes involved in pro- and anti-inflammatory responses. STAT3 has attracted considerable interest as a result of a recent upsurge in study because of their role in directing the innate immune response and sustaining inflammatory pathways, which is a key feature in the pathogenesis of many diseases, including renal disorders. Several pathological conditions which may involve STAT3 include diabetic nephropathy, acute kidney injury, lupus nephritis, polycystic kidney disease, and renal cell carcinoma. STAT3 is expressed in various renal tissues under these pathological conditions. To better understand the role of STAT3 in the kidney and provide a theoretical foundation for STAT3-targeted therapy for renal disorders, this review covers the current work on the activities of STAT3 and its mechanisms in the pathophysiological processes of various types of renal diseases.

ALKBH5 facilitates CYP1B1 mRNA degradation via m6A demethylation to alleviate MSC senescence and osteoarthritis progression.

Improving health and delaying aging is the focus of medical research. Previous studies have shown that mesenchymal stem cell (MSC) senescence is closely related to organic aging and the development of aging-related diseases such as osteoarthritis (OA). m6A is a common RNA modification that plays an important role in regulating cell biological functions, and ALKBH5 is one of the key m6A demethylases. However, the role of m6A and ALKBH5 in MSC senescence is still unclear. Here, we found that the m6A level was enhanced and ALKBH5 expression was decreased in aging MSCs induced by multiple replications, H2O2 stimulation or UV irradiation. Downregulation of ALKBH5 expression facilitated MSC senescence by enhancing the stability of CYP1B1 mRNA and inducing mitochondrial dysfunction. In addition, IGF2BP1 was identified as the m6A reader restraining the degradation of m6A-modified CYP1B1 mRNA. Furthermore, Alkbh5 knockout in MSCs aggravated spontaneous OA in mice, and overexpression of Alkbh5 improved the efficacy of MSCs in OA. Overall, this study revealed a novel mechanism of m6A in MSC senescence and identified promising targets to protect against aging and OA.

Could METS-VF provide a clue as to the formation of kidney stones?

Objective: The lifetime occurrence rate of kidney stones is 14%, making it one of the most prevalent urological conditions. Other contributing elements, such as obesity, diabetes, diet, and heredity, are also taken into account. Our research sought to explore the potential link between high visceral fat scores (METS-VF) and the occurrence of kidney stones, as a means of understanding how to prevent them. Methods: This research utilized data from the National Health and Nutrition Examination Survey (NHANES), mirroring the demographics of the United States. We carried out an in-depth analysis of the connection between METS-VF and kidney stones, based on data from 29,246 participants in the National Health and Nutrition Examination Survey spanning 2007 to 2018, involving logistic regression, segmentation, and dose-response curve analysis. Results: Our study of 29,246 potential participants found that METS-VF was positively associated with the prevalence and progression of kidney stones. After subgroup analysis by gender, race, blood pressure, and blood glucose, our results showed that the ORs for METS-VF and kidney stones were (1.49, 1.44) in males and females, respectively; while in Mexicans, whites, blacks, and In other populations, the OR values were (1.33, 1.43, 1.54, 1.86); in hypertensive and normal populations, the OR values were (1.23, 1.48); in diabetic patients and normoglycemic patients were (1.36,1.43). This proves that it works for all groups of people. Summary: Our studies demonstrate a strong connection between METS-FV and the emergence of kidney stones. It would be beneficial to investigate METS-VF as a marker for kidney stone development and progression in light of these findings.

Antibacterial, injectable, and adhesive hydrogel promotes skin healing.

With the development of material science, hydrogels with antibacterial and wound healing properties are becoming common. However, injectable hydrogels with simple synthetic methods, low cost, inherent antibacterial properties, and inherent promoting fibroblast growth are rare. In this paper, a novel injectable hydrogel wound dressing based on carboxymethyl chitosan (CMCS) and polyethylenimine (PEI) was discovered and constructed. Since CMCS is rich in -OH and -COOH and PEI is rich in -NH2, the two can interact through strong hydrogen bonds, and it is theoretically feasible to form a gel. By changing their ratio, a series of hydrogels can be obtained by stirring and mixing with 5 wt% CMCS aqueous solution and 5 wt% PEI aqueous solution at volume ratios of 7:3, 5:5, and 3:7. Characterized by morphology, swelling rate, adhesion, rheological properties, antibacterial properties, in vitro biocompatibility, and in vivo animal experiments, the hydrogel has good injectability, biocompatibility, antibacterial (Staphylococcus aureus: 56.7 × 107 CFU/mL in the blank group and 2.5 × 107 CFU/mL in the 5/5 CPH group; Escherichia coli: 66.0 × 107 CFU/mL in the blank group and 8.5 × 107 CFU/mL in the 5/5 CPH group), and certain adhesion (0.71 kPa in the 5/5 CPH group) properties which can promote wound healing (wound healing reached 98.02% within 14 days in the 5/5 CPH group) and repair of cells with broad application prospects.

Synthesis of the Disaccharide Core of Ezomycin Nucleosides.

The ezomycins make up a class of complex nucleoside antibiotics that share a common disaccharide core. Herein we present an efficient synthesis of this core from diacetone-d-allose, using a ruthenium-catalyzed asymmetric allylic etherification and a de novo carbohydrate synthesis based on the diastereoselective Henry reaction. Our strategy overcomes several challenges, such as introducing a dense array of functional groups and creating consecutive stereocenters with high selectivity. This approach enables the rapid preparation of disaccharides and paves the way for the total synthesis of ezomycins.

Setmelanotide optimization through fragment-growing, molecular docking in-silico method targeting MC4 receptor.

Obesity has emerged as a global issue, but with the complex structures of multiple related important targets and their agonists or antagonists determined, the mechanism of ligand-protein interaction may offer new chances for developing new generation agonists anti-obesity. Based on the molecule surface of the cryo-EM protein structure 7AUE, we tried to replace D-Ala3 with D-Met in setmelanotide as the linker site for fragment-growing with De novo evolution. The simulation results indicate that the derivatives could improve the binding abilities with the melanocortin 4 receptor and the selectivity over the melanocortin 1 receptor. The improved selectivity of the newly designed derivatives is mainly due to the shape difference of the molecular surface at the orthosteric peptide-binding pocket between melanocortin 4 receptor and melanocortin 1 receptor. The new extended fragments could not only enhance the binding affinities but also function as a gripper to seize the pore, making it easier to balance and stabilize the other component of the new derivatives. Although it is challenging to synthesize the compounds designed in silico, this study may perhaps serve as a trigger for additional anti-obesity research.Communicated by Ramaswamy H. Sarma.