Effect of S-Ketamine on Postoperative Nausea and Vomiting in Patients Undergoing Video-Assisted Thoracic Surgery: A Randomized Controlled Trial.

Purpose: Postoperative nausea and vomiting (PONV) frequently occur in patients after surgery. In this study, the authors investigated whether perioperative S-ketamine infusion could decrease the incidence of PONV in patients undergoing video-assisted thoracoscopic surgery (VATS) lobectomy. Patients and Methods: This prospective, randomized, double-blinded, controlled study was conducted a total of 420 patients from September 2021 to May 2023 at Xuzhou Central Hospital in China, who underwent elective VATS lobectomy under general anesthesia with tracheal intubation. The patients were randomly assigned to either the S-ketamine group or the control group. The S-ketamine group received a bolus injection of 0.5 mg/kg S-ketamine and an intraoperative continuous infusion of S-ketamine at a rate of 0.25 mg/kg/h. The control group received an equivalent volume of saline. All patients were equipped with patient-controlled intravenous analgesia (PCIA), with a continuous infusion rate of 0.03 mg/kg/h S-ketamine in the S-ketamine group or 0.03 µg/kg/h sufentanil in the control group. The primary outcome was the incidence of PONV. Secondary outcomes included perioperative opioid consumption, hemodynamics, postoperative pain, and adverse events. Results: The incidence of PONV in the S-ketamine group (9.7%) was significantly lower than in the control group (30.5%). Analysis of perioperative opioid usage revealed that remifentanil usage was 40.0% lower in the S-ketamine group compared to the control group (1414.8 µg vs 2358.2 µg), while sufentanil consumption was 75.2% lower (33.1 µg vs 133.6 µg). The S-ketamine group demonstrated better maintenance of hemodynamic stability. Additionally, the visual analogue scale (VAS) scores on postoperative day 1 (POD-1) and postoperative day 3 (POD-3) were significantly lower in the S-ketamine group. Finally, no statistically significant difference in other postoperative adverse reactions was observed between the two groups. Conclusion: The results of this trial indicate that perioperative S-ketamine infusion can effectively reduce the incidence of PONV in patients undergoing VATS lobectomy.

An atypical GdpP enzyme linking cyclic nucleotide metabolism to osmotic tolerance and gene regulation in Mycoplasma bovis.

Nucleotide second messengers play an important role in bacterial adaptation to environmental changes. Recent evidence suggests that some of these regulatory molecular pathways were conserved upon the degenerative evolution of the wall-less mycoplasmas. We have recently reported the occurrence of a phosphodiesterase (PDE) in the ruminant pathogen Mycoplasma bovis, which was involved in c-di-AMP metabolism. In the present study, we demonstrate that the genome of this mycoplasma species encodes a PDE of the GdpP family with atypical DHH domains. Characterization of M. bovis GdpP (MbovGdpP) revealed a multifunctional PDE with unusual nanoRNase and single-stranded DNase activities. The alarmone ppGpp was found unable to inhibit c-di-NMP degradation by MbovGdpP but efficiently blocked its nanoRNase activity. Remarkably, MbovGdpP was found critical for the osmotic tolerance of M. bovis under K+ and Na+ conditions. Transcriptomic analyses further revealed the biological importance of MbovGdpP in tRNA biosynthesis, pyruvate metabolism, and several steps in genetic information processing. This study is an important step in understanding the role of PDE and nucleotide second messengers in the biology of a minimal bacterial pathogen.

Eccrine Poroma with Concurrent Basal Cell Carcinoma: A Rare Combination.

Eccrine poroma (EP) is a benign skin appendicular tumor that differentiates into the terminal sweat duct and is often differentiated from basal cell carcinoma (BCC) and seborrheic keratosis. This report describes a 58-year-old woman who presented with left occipital plaque. Histopathological analysis showed that the tumor cells were located in the lower part of the epidermis. The tumor cells were cuboidal or circular basal-like cells of the same size. The surrounding cells were not arranged in a palisade shape. Scattered tumor clusters composed of basal-like cells were also seen in the dermis, staining basophilic, and the surrounding cells were arranged in a palisade pattern. Immunohistochemistry showed that BerEP4, epithelial membrane antigen EMA, carcinoembryonic antigen CEA, Bcl-2, CD10, CK7 were positive, AR, PAS were negative. According to the pathological examination and immunohistochemical results, a case of eccrine poroma with concurrent basal cell carcinoma was diagnosed.

[Advances in gene editing and natural product synthesis of Rhodotorula toruloides].

Rhodotorula toruloides is a non-conventional red yeast that can synthesize various carotenoids and lipids. It can utilize a variety of cost-effective raw materials, tolerate and assimilate toxic inhibitors in lignocellulosic hydrolysate. At present, it is widely investigated for the production of microbial lipids, terpenes, high-value enzymes, sugar alcohols and polyketides. Given its broad industrial application prospects, researchers have carried out multi-dimensional theoretical and technological exploration, including research on genomics, transcriptomics, proteomics and genetic operation platform. Here we review the recent progress in metabolic engineering and natural product synthesis of R. toruloides, and prospect the challenges and possible solutions in the construction of R. toruloides cell factory.

Ambient particulate matter exposure plus a high-fat diet exacerbate renal injury by activating the NLRP3 inflammasome and TGF-ß1/Smad2 signaling pathway in mice.

BACKGROUND: Chronic kidney disease (CKD) is a public health problem of which the prevalence is increasing worldwide. Several studies have reported that ambient particulate matter (PM) causes kidney injury, which may be related to the risk of CKD. However, the underlying molecular mechanisms have not been fully clarified. In addition, whether a high-fat diet (HFD) could exacerbate ambient PM-induced nephrotoxicity has not been evaluated. This study aimed to investigate the combined effect of ambient PM and a HFD on renal injury. METHODS AND RESULTS: Male C57BL/6 J mice were fed either a normal diet or a HFD and exposed to filtered air (FA) or particulate matter (PM) for 18 weeks. In the present study, we observed that renal function changed (serum blood urea nitrogen and serum creatinine), and exposure to PM and a HFD caused a synergistic effect on renal injury. Histopathological analysis showed that PM exposure induced renal fibrosis in mice, and combined exposure to PM and a HFD exacerbated these adverse effects. Moreover, ambient PM exposure activated the nucleotide-binding domain and leucine-rich repeat protein 3 (NLRP3) inflammasome and increased the inflammatory response, as indicated by the increases in interleukin-1ß, interleukin-6 and tumor necrosis factor-α in the serum and kidney, as well as the upregulation of specific renal fibrosis-related markers (transforming growth factor-ß1 and p-Smad2) in the kidney tissues of mice. Furthermore, combined exposure to PM and a HFD augmented these changes in the kidney. In vitro, inhibition of the NLRP3 inflammasome by MCC950 (an inhibitor of NLRP3) reduced the levels of proinflammatory cytokines and the expression of transforming growth factor-ß1 and p-Smad2 in HK-2 cells. CONCLUSION: Taken together, our data indicated that PM exposure caused renal inflammation and induced profibrotic effects on the kidney, and combined exposure to ambient PM and a HFD exacerbated renal injury, which may involve activation of the NLRP3 inflammasome and the TGF-ß1/Smad2 signaling pathway.

The Preparation and Properties of Composite Hydrogels Based on Gelatin and (3-Aminopropyl) Trimethoxysilane Grafted Cellulose Nanocrystals Covalently Linked with Microbial Transglutaminase.

Mechanically enhanced gelatin-based composite hydrogels were developed in the presence of functionalized cellulose nanocrystals (CNCs) employing microbial transglutaminase (mTG) as a binding agent. In this work, the surfaces of CNCs were grafted with (3-Aminopropyl) trimethoxysilane with a NH2 functional group, and the success of CNCs' modification was verified by FTIR spectroscopy and XPS. The higher degree of modification in CNCs resulted in more covalent cross-linking and dispersibility within the gelatin matrix; thus, the as-prepared hydrogels showed significantly improved mechanical properties and thermo-stability, as revealed by dynamic rheological analysis, uniaxial compression tests and SEM. The biocompatibility of the obtained hydrogels was evaluated by the MTT method, and it was found that the grafted CNCs had no obvious inhibitory effect on cell proliferation. Hence, the mechanically enhanced gelatin-based hydrogels might have great potential in biomedical applications.

Health utility of children with acute lymphoblastic leukemia in China.

Background: Acute lymphoblastic leukemia is the most common cancer in children. As the 5-year survival rate has been improved to over 80%, more emphasis is now placed on reducing therapy toxicities and enhancing health-related quality of life (HRQoL) of patients during treatment. Our objective was to measure health utility of pediatric acute lymphoblastic leukemia (pALL) patients in China, examine utility weights of different treatment phases and influencing factors of health utility, as well as identify which aspects of HRQoL were most impaired. Methods: A cross-sectional study was conducted in Shanghai Children's Medical Center (SCMC) Affiliated to Shanghai Jiao Tong University School of Medicine in China from April to November 2021. Primary caregivers of 247 patients completed the assessment by CHU9D-CHN and health utility scores were computed for all the patients and stratified by treatment phases. Various multivariable models were constructed and the best was chosen to identify independent factors associated with utility scores. Factors affecting the most impaired dimensions were also examined. Results: The overall mean (SD) health utility score was 0.79 (±0.17) and significantly increased from induction (0.73 [±0.19], P < 0.001) to consolidation (0.74 [±0.18]), and to maintenance (0.82 [±0.16]). After adjusting for potentially influencing factors, utility scores in induction (Beta = -0.086, P = 0.005) and consolidation (Beta = -0.074, P = 0.043) were constantly lower than those during maintenance. In item-level analysis, lower age and induction phase were found to be significantly associated with high severity reported on the "school work/homework" dimension. Additionally, only the induction phase (vs. maintenance, OR = 2.24, P = 0.016) was independently associated with the high severity level reported on the "able to join in activities" dimension. Conclusions: This is the first study that measured health utility of children with pALL in China. Mean health utility scores increased from induction to maintenance. These provided important utility estimates that help inform future health economic models. The phrasing of "School work/homework" in CHU9D-CHN could be further improved. More efforts are needed to design and implement specific interventions targeting at the dimension "able to join in activities" for enhancing HRQoL of children with pALL in China.

PIWI-interacting RNAs are aberrantly expressed and may serve as novel biomarkers for diagnosis of lung adenocarcinoma.

BACKGROUND: Lung adenocarcinoma (LUAD) is the main subtype of primary lung cancer and is a leading cause of cancer-related death worldwide. PIWI-interacting RNAs (piRNAs) are a type of small non-coding RNAs that may play crucial roles in cancer progression and serve as biomarkers for tumor detection. This study aimed to explore the expression profiles and diagnostic values of piRNAs in LUAD. METHODS: Small RNA sequencing was performed to investigate tissue piRNA profiles of LUAD. The expression of selected upregulated piRNAs were detected in tissues and serum exosome samples by quantitative real-time polymerase chain reaction (qRT-PCR). Serum exosomes were identified by transmission electron microscope, nanoparticle tracking analysis, and western blot analysis. Receiver operating characteristic (ROC) curve was adopted to quantify the diagnostic potentials of piRNAs in LUAD. Finally, a piRNA panel was developed by multivariate logistic regression model. RESULTS: We identified that 76 piRNAs were overexpressed and 9 piRNAs were underexpressed in LUAD tissues compared with adjacent non-tumor tissues. Among the top 10 overexpressed piRNAs, 4 piRNAs (piR-hsa-26925, piR-hsa-5444, piR-hsa-30636, and piR-hsa-8757) were verified by qRT-PCR to be significantly upregulated in LUAD tissues. Moreover, piR-hsa-26925 and piR-hsa-5444 had a significantly higher level in serum exosome samples of LUAD patients than those of healthy controls. We finally established a 2-piRNA panel composed of piR-hsa-26925 and piR-hsa-5444, which showed higher diagnostic performance for LUAD with an AUC of 0.833. CONCLUSIONS: Our finding revealed the abnormally expressed piRNAs in LUAD, and serum exosomal piR-hsa-26925 and piR-hsa-5444 could serve as potential biomarkers for LUAD diagnosis.

Preparation and characterization of enzymatically cross-linked gelatin/cellulose nanocrystal composite hydrogels.

Gelatin is an attractive hydrogel material because of its excellent biocompatibility and non-cytotoxicity, but poor mechanical properties of gelatin-based hydrogels become a big obstacle that limits their wide-spread application. To solve it, in this work, gelatin/cellulose nanocrystal composite hydrogels (Gel-TG-CNCs) were prepared using microbial transglutaminase (mTG) as the crosslinking catalyst and cellulose nanocrystals (CNCs) as reinforcements. The physicochemical properties of the composite hydrogels were investigated by thermogravimetric analysis (TGA), X-ray diffraction (XRD) and scanning electron microscopy (SEM). The dynamic rheological measurement and uniaxial compression test were performed to study the effects of mTG and CNC contents on the storage modulus and breaking strength of the as-prepared Gel-TG-CNCs. Results showed that the addition of CNCs and mTG could significantly increase the storage modulus and breaking strength of gelatin-based hydrogels, especially when added simultaneously. The breaking strength of Gel-TG-CNCs (2%) at 25 °C can reach 1000 g which is 30 times greater than pure gelatin hydrogels. The biocompatibility of the composite hydrogels was also investigated by the MTT method with Hela cells, and the results demonstrated that the composite hydrogels maintained excellent biocompatibility. With a combination of good biocompatibility and mechanical properties, the as-prepared Gel-TG-CNCs showed potential application value in the biomedical field.

The photophysical properties and imaging application of a new polarity-sensitive fluorescent probe.

A new excited-state intramolecular proton transfer (ESIPT) based and polarity-sensitive fluorescent probe M-HA was easily developed by conjugated connection of indole and 2'-hydroxyacetophenone through (E)-2-chloro-3-(hydroxymethylene)cyclohex-1-enecarbaldehyde. M-HA shows near-infrared fluorescence, high molar absorption coefficient and a large Stokes shift in various common solvents. In particular, M-HA exhibits red-shifted maximum emission wavelength, and extraordinarily high fluorescence intensity and quantum yield in high-polarity solvents. The theoretical calculation results indicate that the reduced electron-vibration coupling related to out-of-plane motions of benzene units in more polar solvents is mainly responsible for such unusual photophysical properties. For further application, M-HA was utilized to image live cells. The confocal fluorescence imaging results demonstrate that M-HA possesses excellent membrane permeability and can fluoresce brightly in the cytoplasm. Overall, M-HA, as a polarity-sensitive fluorescent probe, will serve as an excellent tool for quantitative determination of polarity in vitro and in-depth study of the polarity biology in physiopathology in future.

An emerging role for cyclic dinucleotide phosphodiesterase and nanoRNase activities in Mycoplasma bovis: Securing survival in cell culture.

Mycoplasmas are host-restricted prokaryotes with a nearly minimal genome. To overcome their metabolic limitations, these wall-less bacteria establish intimate interactions with epithelial cells at mucosal surfaces. The alarming rate of antimicrobial resistance among pathogenic species is of particular concern in the medical and veterinary fields. Taking advantage of the reduced mycoplasma genome, random transposon mutagenesis was combined with high-throughput screening in order to identify key determinants of mycoplasma survival in the host-cell environment and potential targets for drug development. With the use of the ruminant pathogen Mycoplasma bovis as a model, three phosphodiesterases of the DHH superfamily were identified as essential for the proliferation of this species under cell culture conditions, while dispensable for axenic growth. Despite a similar domain architecture, recombinant Mbov_0327 and Mbov_0328 products displayed different substrate specificities. While rMbovP328 protein exhibited activity towards cyclic dinucleotides and nanoRNAs, rMbovP327 protein was only able to degrade nanoRNAs. The Mbov_0276 product was identified as a member of the membrane-associated GdpP family of phosphodiesterases that was found to participate in cyclic dinucleotide and nanoRNA degradation, an activity which might therefore be redundant in the genome-reduced M. bovis. Remarkably, all these enzymes were able to convert their substrates into mononucleotides, and medium supplementation with nucleoside monophosphates or nucleosides fully restored the capacity of a Mbov_0328/0327 knock-out mutant to grow under cell culture conditions. Since mycoplasmas are unable to synthesize DNA/RNA precursors de novo, cyclic dinucleotide and nanoRNA degradation are likely contributing to the survival of M. bovis by securing the recycling of purines and pyrimidines. These results point toward proteins of the DHH superfamily as promising targets for the development of new antimicrobials against multidrug-resistant pathogenic mycoplasma species.

Mbov_0503 Encodes a Novel Cytoadhesin that Facilitates Mycoplasma bovis Interaction with Tight Junctions.

Molecules contributing to microbial cytoadhesion are important virulence factors. In Mycoplasma bovis, a minimal bacterium but an important cattle pathogen, binding to host cells is emerging as a complex process involving a broad range of surface-exposed structures. Here, a new cytoadhesin of M. bovis was identified by producing a collection of individual knock-out mutants and evaluating their binding to embryonic bovine lung cells. The cytoadhesive-properties of this surface-exposed protein, which is encoded by Mbov_0503 in strain HB0801, were demonstrated at both the mycoplasma cell and protein levels using confocal microscopy and ELISA. Although Mbov_0503 disruption was only associated in M. bovis with a partial reduction of its binding capacity, this moderate effect was sufficient to affect M. bovis interaction with the host-cell tight junctions, and to reduce the translocation of this mycoplasma across epithelial cell monolayers. Besides demonstrating the capacity of M. bovis to disrupt tight junctions, these results identified novel properties associated with cytoadhesin that might contribute to virulence and host colonization. These findings provide new insights into the complex interplay taking place between wall-less mycoplasmas and the host-cell surface.

Two-photon fluorescence visualization of lysosomal pH changes during mitophagy and cell apoptosis.

We herein develop a novel two-photon fluorescent probe termed L-pH for visualization of lysosomal pH within live cells. L-pH is composed of three moieties, including naphthalimide fluorophore as a fluorescence off-on response moiety, piperazine and morpholine groups as lysosomal targeting and pH responsive sites, as well as a reactive benzyl chloride segment for further lysosomal anchoring. The experimental results demonstrate that L-pH can instantaneously respond to various pH values with high sensitivity and selectivity, and has low cytotoxicity and excellent photostability. The one-photon and two-photon fluorescence imaging data indicate L-pH can preferably accumulate into lysosome and monitor the rise of lysosomal pH changes during myriad cell stress conditions, including heat shock, cell apoptosis and mitophagy. Moreover, L-pH was applied for imaging of pH difference in abdominal tissues of mice. L-pH will be a potential tool for monitoring lysosomal pH variation during lysosome-associated physiological and pathological states.

Calves Infected with Virulent and Attenuated Mycoplasma bovis Strains Have Upregulated Th17 Inflammatory and Th1 Protective Responses, Respectively.

Mycoplasma bovis is a critical bovine pathogen, but its pathogenesis remains poorly understood. Here, the virulent HB0801 (P1) and attenuated HB0801-P150 (P150) strains of M. bovis were used to explore the potential pathogenesis and effect of induced immunity from calves' differential transcriptomes post infection. Nine one-month-old male calves were infected with P1, P150, or mock-infected with medium and euthanized at 60 days post-infection. Calves in P1 group exhibited other clinical signs and pathological changes compared to the other two groups. Transcriptome profiles of peripheral blood mononuclear cells revealed seven and 10 hub differentially expressed genes (DEGs) in P1 and P150 groups compared with mock-infected group, respectively. Then, P1-induced pathogenesis was predicted to be associated with enhanced Th17, and P150-induced immunity with Th1 response and expression of ubiquitination-associated enzymes. Association analysis showed that 14 and 11 DEGs were positively and negatively correlated with pathological changes, respectively. Furthermore, up-regulated expression in molecules critical to differentiation of pathogenic Th17 cells in lung and peripheral blood mononuclear cells in P1 group was validated at RNA and protein levels. The results confirmed virulent and attenuated strains might be associated with biased differentiation of pro-inflammatory pathogenic Th17 and Th1 subsets respectively.

Monitoring mitochondrial pH with a hemicyanine-based ratiometric fluorescent probe.

Mitochondria as essential organelles play critical roles in cellular metabolism. Mitochondrial pH is a vital parameter that directly affects the unique function of mitochondria. Herein, we present a new ratiometric fluorescent probe M-pH for monitoring the pH within the mitochondria. M-pH consists of a stable and large π-electron conjugated merocyanine system. The lipophilic cationic benzyl group will facilitate the accumulation of M-pH in mitochondria. The phenol unit is the recognition moiety, achieving the ratiometric sensing of pH changes. The experimental results indicate that M-pH displays ratiometric fluorescence response to different pH values. Meanwhile, M-pH shows negligible response to common species, and has high stability and low cytotoxicity. In biological experiments, M-pH can solely accumulate in mitochondria and visualize the pH changes during mitophagy and cell apoptosis. We thus believe that M-pH has great potential as a practical tool for real-time monitoring of pH changes of mitochondria, contributing to revealing the pathogenesis of mitochondrial pH associated diseases.

CPT, the main test method of skin neuronal sensitivity.

BACKGROUND: Many scholars concentrate on skin barrier disruption of sensitive skin, but few focus on its increased neuronal sensitivity. OBJECTIVE: To study the possibility of using current perception threshold (CPT) measurement for the quantitative evaluation of skin neuronal sensitivity combined with stinging test. METHODS: The amount of 50 µL 10% lactic acid was applied on each side of the nasolabial fold at random. Subjects assessed stinging based on a 4-point scale at 30 s, 2.5 min and 5.0 min. CPT and transepidermal water loss (TEWL) were measured before and after stinging test. Subjects were divided into different groups based on their response to lactic acid. RESULTS: There was a positive correlation between CPTbefore and the sum of clinical scores (CSs). While the beginning time of stinging (BT) was shortened, the CPTbefore decreased and TEWL increased. CONCLUSION: Different degrees of skin susceptibility can be reflected by BT. CPT can be useful for the quantitative evaluation of skin neuronal sensitivity.