Addition of liposomal bupivacaine to standard bupivacaine versus standard bupivacaine alone in the supraclavicular brachial plexus block: a randomized controlled trial.

BACKGROUND: The analgesic effect of adding liposomal bupivacaine to standard bupivacaine in supraclavicular brachial plexus block is not known. We hypothesized that addition of liposomal bupivacaine would reduce acute postoperative pain compared to standard bupivacaine alone. METHODS: A randomized controlled trial was conducted. Patients and outcome assessors were blinded. Eighty patients undergoing distal radial fracture fixation under regional anesthesia with supraclavicular brachial plexus block were randomized into two groups. The liposomal bupivacaine (LB-BPB) group received 10ml of 0.5% plain bupivacaine immediately followed by 10ml of 1.33% liposomal bupivacaine (n=40). The standard bupivacaine (S-BPB) group received 20ml of 0.5% plain bupivacaine (n=40). The primary outcome was weighted area under curve (AUC) numerical rating scale (NRS) pain score at rest over the first 48 hours after surgery. Secondary outcomes included AUC scores for pain with movement, overall benefit with analgesia score (OBAS) and other functional scores. RESULTS: For the primary outcome, LB-BPB group was associated with statistically significantly lower AUC pain score at rest (0.6 vs 1.4, p-value < 0.001) in the first 48 hours. Of the secondary outcomes, no difference between treatment groups reached statistical significance with the exception of AUC score for pain with movement (2.3 vs 3.7, adjusted p-value < 0.001) and OBAS (1.1 vs 1.7, adjusted p-value = 0.020) in the first 48 hours, as well as NRS pain score at rest (0.5 vs 1.9, adjusted p-value < 0.001) and with movement (2.7 vs 4.9, adjusted p-value < 0.001) on postoperative day (POD) 1. Differences in NRS pain scores on POD2, POD3 and POD4 did not reach the level of statistical significance. There were no statistically significant differences in sensory function. CONCLUSION: Liposomal bupivacaine given via supraclavicular brachial plexus block reduced pain at rest in the early postoperative period.

Additive-free selective oxidation of aromatic alcohols with molecular oxygen catalyzed by a mixed-valence polyoxovanadate-based metal-organic framework.

Selective oxidation of alcohols to aldehydes is an industrially significant chemical transformation. Herein, we report a mixed-valence polyoxovanadate-based metal-organic framework (MOF), (H2bix)5{[Cd(bix)2][VIV8VV7O36Cl]2}·3H2O (V-Cd-MOF), for catalyzing the additive-free oxidation of a series of aromatic alcohols with high selectivity and in nearly quantitative yield to the corresponding aldehydes with O2 as the oxidant. Experimental results, corroborated with density functional theory calculations, indicate that it is the synergistic operation of the dual active sites of the VIV-O-VV building units in the polyoxovanadate cluster that is responsible for the excellent catalytic performance observed: on the one hand, the exposed and readily accessible reduced VIV site is believed to activate O2, resulting in a reactive oxygen species for the subsequent activation and breaking of the substrate's Cα-H bond. On the other hand, the VV site coordinates with the alcoholic O atom to facilitate the cleavage of the O-H bond. The catalyst can be recycled by centrifugation and re-used at least five times with uncompromised performance. To our knowledge, V-Cd-MOF represents the first example of a polyoxometalate-based MOF catalyst for additive-free selective oxidation of alcohol to aldehyde with O2 as an oxidant.

Use of pain-related gene features to predict depression by support vector machine model in patients with fibromyalgia.

The prevalence rate of depression is higher in patients with fibromyalgia syndrome, but this is often unrecognized in patients with chronic pain. Given that depression is a common major barrier in the management of patients with fibromyalgia syndrome, an objective tool that reliably predicts depression in patients with fibromyalgia syndrome could significantly enhance the diagnostic accuracy. Since pain and depression can cause each other and worsen each other, we wonder if pain-related genes can be used to differentiate between those with major depression from those without. This study developed a support vector machine model combined with principal component analysis to differentiate major depression in fibromyalgia syndrome patients using a microarray dataset, including 25 fibromyalgia syndrome patients with major depression, and 36 patients without major depression. Gene co-expression analysis was used to select gene features to construct support vector machine model. The principal component analysis can help reduce the number of data dimensions without much loss of information, and identify patterns in data easily. The 61 samples available in the database were not enough for learning based methods and cannot represent every possible variation of each patient. To address this issue, we adopted Gaussian noise to generate a large amount of simulated data for training and testing of the model. The ability of support vector machine model to differentiate major depression using microarray data was measured as accuracy. Different structural co-expression patterns were identified for 114 genes involved in pain signaling pathway by two-sample KS test (p < 0.001 for the maximum deviation D = 0.11 > D critical = 0.05), indicating the aberrant co-expression patterns in fibromyalgia syndrome patients. Twenty hub gene features were further selected based on co-expression analysis to construct the model. The principal component analysis reduced the dimension of the training samples from 20 to 16, since 16 components were needed to retain more than 90% of the original variance. The support vector machine model was able to differentiate between those with major depression from those without in fibromyalgia syndrome patients with an average accuracy of 93.22% based on the expression levels of the selected hub gene features. These findings would contribute key information that can be used to develop a clinical decision-making tool for the data-driven, personalized optimization of diagnosing depression in patients with fibromyalgia syndrome.

LncRNA SNHG3 Promotes Sevoflurane-Induced Neuronal Injury by Activating NLRP3 via NEK7.

BACKGROUND: Early exposure to sevoflurane may cause brain tissue degeneration; however, the mechanism involved in this process has not been explored. In this study, we investigated the role of long non-coding RNA small nucleolar RNA host gene 3 (lncRNA SNHG3) in sevoflurane-induced neuronal injury. METHODS: The injury models of HT22 and primary cultures of neurons were constructed using sevoflurane treatment. The WST-8 reduction was detected by CCK-8 assay, the level of inflammatory factors was detected by enzyme-linked immunosorbent assay (ELISA), and cell pyroptosis was detected by flow cytometry. The expression of genes and proteins was detected by qRT-PCR and Western blot, respectively. The level of ß-tubulin III in primary cultures of hippocampal neurons was analyzed by immunofluorescence. The relationship among SNHG3, PTBP1 and NEK7 was confirmed by RIP assay. RESULTS: The expression of SNHG3 and NEK7 were enhanced in sevoflurane-treated HT22 cells. Sevoflurane inhibited the WST-8 reduction in a concentration-dependent manner, promoted the pyroptosis, and increased pyroptosis-related protein expression. SNHG3 knockdown significantly inhibited sevoflurane-induced pyroptosis and inflammatory injury in HT22 cells and primary cultures of neurons. Furthermore, SNHG3 regulated NEK7 expression by binding to PTBP1. NEK7 knockdown reversed the decrease in WST-8 reduction, inhibited pyroptosis, and decreased the release of inflammatory factors and pyroptosis-related protein expression by inactivation of NLRP3 signaling in sevoflurane-induced HT22 cells. Moreover, NEK7 overexpression attenuated the effect of SNHG3 knockdown on neuronal pyroptosis and inflammation injury. CONCLUSION: Downregulation of SNHG3 attenuates sevoflurane-induced neuronal inflammation and pyroptosis by mediating the NEK7/NLRP3 axis, suggesting that SNHG3 could be a potential target gene for neuronal injury.

The analgesic effect of total intravenous anaesthesia with propofol versus inhalational anaesthesia for acute postoperative pain after hepatectomy: a randomized controlled trial.

BACKGROUND: Postoperative pain control can be challenging in patients undergoing hepatectomy. A previous retrospective study on hepatobiliary/ pancreatic surgeries showed better postoperative pain control in patients who received propofol TIVA. The aim of this study was to determine the analgesic effect of propofol TIVA for hepatectomy. This clinical study has been registered at ClinicalTrials.gov (NCT03597997). METHODS: A prospective randomized controlled trial was performed to compare the analgesic effect of propofol TIVA versus inhalational anaesthesia. Patients aged between 18 and 80 years old with an American Society of Anesthesiologist (ASA) physical status of I-III scheduled for elective hepatectomy were recruited. Ninety patients were randomly allocated to receive either propofol TIVA (TIVA group) or inhalational anaesthesia with sevoflurane (SEVO group). Perioperative anaesthetic/analgesic management was the same for both groups. Numerical rating scale (NRS) pain scores, postoperative morphine consumption, quality of recovery, patient satisfaction and adverse effects were evaluated during the acute postoperative period and at 3 and 6 months after surgery. RESULTS: No significant differences were found for acute postoperative pain scores (both at rest and during coughing) and postoperative morphine consumption between TIVA and SEVO groups. Patients given TIVA had lower pain scores with coughing at 3 months after surgery (p = 0.014, and FDR < 0.1). TIVA group was associated with better quality of recovery on postoperative day (POD) 3 (p = 0.038, and FDR < 0.1), less nausea (p = 0.011, and FDR < 0.1 on POD 2; p = 0.013, and FDR < 0.1 on POD 3) and constipation (p = 0.013, and FDR < 0.1 on POD 3). CONCLUSION: Propofol TIVA did not improve acute postoperative pain control compared to inhalational anaesthesia in patients who underwent hepatectomy. Our results do not support the use of propofol TIVA for reducing acute postoperative pain after hepatectomy.

Analgesic Effect of Buprenorphine for Chronic Noncancer Pain: A Systematic Review and Meta-analysis of Randomized Controlled Trials.

BACKGROUND: Buprenorphine is a partial agonist at the µ-opioid receptor and an antagonist at the delta and kappa opioid receptors. It has high affinity and low intrinsic activity at the µ-opioid receptor. Buprenorphine demonstrates no ceiling effect for clinical analgesia, but demonstrates this for respiratory depression and euphoria. It may provide effective analgesia while producing less adverse effects, making it a promising opioid analgesic. A systematic review and meta-analysis were performed to examine the analgesic efficacy of buprenorphine for patients with chronic noncancer pain. METHODS: PubMed, MEDLNE, Embase, and the Cochrane Library were searched up to January 2022. Randomized controlled trials were included if they compared buprenorphine versus placebo or active analgesic in patients with chronic noncancer pain, where pain score was an outcome. Nonrandomized controlled trials, observational studies, qualitative studies, case reports, and commentaries were excluded. Two investigators independently performed the literature search, study selection, and data collection. A random-effects model was used. The primary outcome was the effect of buprenorphine on pain intensity in patients with chronic noncancer pain based on standardized mean difference (SMD) in pain score. Quality of evidence was assessed using the Grade of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: Two separate literature searches were conducted for patients with and without opioid use disorder (OUD). Only one study met the search criteria for those with OUD. Fourteen randomized controlled trials were included for those without OUD. Buprenorphine was associated with reduced pain score (SMD = -0.368, P < .001, I 2 = 89.37%) compared to placebo or active analgesic. Subgroup meta-analyses showed statistically significant differences in favor of buprenorphine versus placebo (SMD = -0.404, P < .001), for chronic low back pain (SMD = -0.383, P < .001), when administered via the transdermal route (SMD = -0.572, P = .001), via the buccal route (SMD = -0.453, P < .001), with length of follow-up lasting <12 weeks (SMD = -0.848, P < .05), and length of follow-up lasting 12 weeks or more (SMD = -0.415, P < .001). There was no significant difference when compared to active analgesic (SMD = 0.045, P > .05). Quality of evidence was low to moderate. CONCLUSIONS: Buprenorphine was associated with a statistically significant and small reduction in pain intensity compared to placebo. Both the transdermal and buccal routes provided pain relief. There was more evidence supporting its use for chronic low back pain.

Regenerative medicine for the treatment of chronic low back pain: a narrative review.

Low back pain (LBP) is a common and important clinical problem. In addition to pain, patients are also affected by personal, social, and economic burdens. Intervertebral disc (IVD) degeneration is a common cause of LBP, further increasing the patient's morbidity and medical costs. The limitations of current treatment strategies for long-term pain relief mean that increasing attention has been paid to regenerative medicine. We carried out a narrative review to explore the roles of four types of regenerative medicine for treating LBP: marrow-derived stem cells, growth factors, platelet-rich plasma, and prolotherapy. Marrow-derived stem cells are regarded as an ideal cell source for IVD regeneration. Growth factors may stimulate the synthesis of extracellular matrix and attenuate or reverse the degenerative process in IVD, while platelet-rich plasma, which contains multiple growth factors, is thought to be a promising alternative therapy for IVD degeneration. Prolotherapy can initiate the body's inflammatory healing response to repair injured joints and connective tissues. This review summarizes the mechanisms, in vitro and in vivo studies, and clinical applications of these four types of regenerative medicine in patients with LBP.

Construction of Frustrated Lewis Pair Sites in CeO2-C/BiVO4 for Photoelectrochemical Nitrate Reduction.

Photoelectrochemical nitrate reduction reaction (PEC NIRR) could convert the harmful pollutant nitrate (NO3-) to high-value-added ammonia (NH3) under mild conditions. However, the catalysts are currently hindered by the low catalytic activity and slow kinetics. Here, we reported a heterostructure composed of CeO2 and BiVO4, and the "frustrated Lewis pairs (FLPs)" concept was introduced for understanding the role of Lewis acids and Lewis bases on PEC NIRR. The electron density difference maps indicated that FLPs were significantly active for the adsorption and activation of NO3-. Furthermore, carbon (C) improved the carrier transport ability and kinetics, contributing to the NH3 yield of 21.81 µg h-1 cm-2. The conversion process of NO3- to NH3 was tracked by 15NO3- and 14NO3- isotopic labeling. Therefore, this study demonstrated the potential of CeO2-C/BiVO4 for efficient PEC NIRR and provided a unique mechanism for the adsorption and activation of NO3- over FLPs.

Novel multi-component crystals of berberine with improved pharmaceutical properties.

As an extremely popular natural product, berberine (BER) is mainly used for gastroenteritis and diarrhoea caused by bacteria. Research has also revealed the potent and extensive pharmacological properties of BER including its anti-arrhythmic, anti-tumour, anti-inflammatory and hypoglycemic activities and so on; therefore, BER is a promising drug for further development. However, its commercial form with hydrochloride exhibits poor stability and solubility, which are detrimental to its clinical therapeutic effects. For these purposes, the salt form was regulated via the reactive crystallization of 8-hydroxy-7,8-dihydroberberine (8H-HBER) with five pharmaceutically suitable organic acids including malonic acid (MA), L-tartaric acid (LTA), D-tartaric acid (DTA), DL-tartaric acid (DLTA) and citric acid (CA), resulting in the six novel solid forms 1BER-1LTA-1W, 1BER-1DTA-1W, 1BER-1DLTA and 2BER-2CA as well as two rare multi-stoichiometric solid forms 1BER-1MA and 1BER-2MA-2W. The preparation of the multi-stoichiometric products was greatly influenced by both the crystallization solvent type and the molar ratio of reactants. The structures of these multi-component solid forms were determined using single-crystal X-ray diffraction and further characterized by powder X-ray diffraction, thermal analysis and Fourier transform infrared spectroscopy. Stability experiments showed that all samples prepared had superior physical stability under high temperature and high humidity. Furthermore, dissolution experiments demonstrated that the maximum apparent solubilities (MAS) of all the products were significantly improved compared with the commercial form of BER in dilute hydrochloric solution (pH = 1.2). In particular, the MAS of 1BER-1MA in dilute hydrochloric solution is as high as 34 times that of the commercial form. In addition, it is preliminarily confirmed that the MAS of the samples prepared in pure water and dilute hydrochloric solution is primarily influenced by a combination of factors including the packing index, intermolecular interactions, affinity of the counter-ion to the solvent, the molar ratio of the drug to counter-ion in the product and the common ion effect. These novel solids are potential candidates for BER solid forms with improved oral dosage design and may prompt further development.

Bioinformatics analysis and function prediction of NBS-LRR gene family in Broussonetia papyrifera.

Most of the currently available disease resistance (R) genes have NBS (nucleotide-binding site) and LRR (leucine-rich-repeat) domain which belongs to the NBS-LRR gene family. The whole genome sequencing of Broussonetia papyrifera provides an important bioinformatics database for the study of the NBS-LRR gene family. In this study, 328 NBS-LRR family genes were identified and classified in B. papyrifera according to different classification schemes, where there are 92 N types, 47 CN type, 54 CNL type, 29 NL types, 55 TN type, and 51 TNL type. Subsequently, we conducted bioinformatics analysis of the NBS-LRR gene family. Classification, motif analysis of protein sequences, and phylogenetic tree studies of the NBS-LRR genes in B. papyrifera provide important basis for the functional study of NBS-LRR family genes. Additionally, we performed structural analysis of the chromosomal location, physicochemical properties, and sequences identified by genetic characterization. In addition, through the analysis of GO enrichment, it was found that NBS-LRR genes were involved in defense responses and were significantly enriched in biological stimulation, immune response, and abiotic stress. In addition, we found that Bp06g0955 was the most sensitive to low temperature and encoded the RPM1 protein by analyzing the low temperature transcriptome data of B. papyrifera. Quantitative results of gene expression after 48 h of Fusarium infection showed that Bp01g3293 increased 14 times after infection, which encodes RPM1 protein. The potential of NBS-LRR gene responsive to biotic and abiotic stresses can be exploited to improve the resistance of B. papyrifera.

Quantitative Analysis the Weak Non-Covalent Interactions of the Polymorphs of Donepezil.

Donepezil has polymorphism. Different crystalline forms can exhibit different physicochemical properties and biological activities. Exploration of intermolecular interactions is essential to reveal the formation mechanism and differences in properties of polymorphs. This study explores the weak non-covalent intermolecular interactions of donepezil polymorphs through fully ab initio quantum mechanical methods, semi-empirical methods, and Hirshfeld surface analysis. The results show that the Hirshfeld surface analysis method can clearly and intuitively reveal the intermolecular interactions. Theoretical calculations using the atom-atom Coulomb-London-Pauli (AA-CLP) method were also performed to understand the interaction energies toward the total lattice energy. The value of the lattice energy was in accordance with the melting points of the donepezil polymorphs and brought to light the nature of thermal stability. In the specific energy distribution, the contribution of the dispersion force is the most prominent. Further interaction energy analysis found that within a distance of 3.8 Å from the center of the donepezil molecule, different crystalline forms of donepezil molecules have different interaction energies with surrounding molecules. The different interaction energies between polymorphs may lead to polymorphs with different physical-chemical properties.

First Description of the Mitogenome Features of Neofoleyellides Genus (Nematoda: Onchocercidae) Isolated from a Wild Bird (Pyrrhocorax pyrrhocorax).

The Onchocercidae family is composed of more than 30 valid nematode species with notable zoonotic potential. Current limitations in molecular characterization methods and species identification are the main obstacles to a better understanding of the biology of Onchocercidae species, particularly in wildlife. This study describes for the first time the complete mitochondrial (mt) genome sequence of Neofoleyellides sp. isolated from a wild bird (Pyrrhocorax pyrrhocorax) and belonging to the Neofoleyellides genus (Nematoda: Onchocercidae). The mt genome of Neofoleyellides sp. (GenBank accession number: ON641583) was a typical circular DNA molecule of 13,628 bp in size with an AT content of 76.69%. The complete mt genome comprised 36 functional subunits, including 12 protein-coding genes (PCGs), 2 ribosomal RNA genes, and 22 transfer RNA genes. The most common start codon was ATT/ATG except for nad2 with TTG, and TAA was the termination codon for all protein-coding genes (PCGs). Phylogenetic analysis of the concatenated and aligned amino acid sequences of the 12 PCGs showed that the trees generated using different methods (Bayesian inference and maximum likelihood) with different partition schemes shared similar topologies. The isolated Neofoleyellides sp. was placed in the Onchocercidae family and formed a sister branch with the genera Onchocerca and Dirofilaria. The entire mt genome of Neofoleyellides sp. presented in this study could provide useful data for studying the population genetics and phylogenetic relationships of Onchocercidae species.

A microRNA-microRNA crosstalk network inferred from genome-wide single nucleotide polymorphism variants in natural populations of Arabidopsis thaliana.

To adapt to variable natural conditions, plants have evolved several strategies to respond to different environmental stresses. MicroRNA (miRNA)-mediated gene regulation is one of such strategies. Variants, e.g., single nucleotide polymorphisms (SNPs) within the mature miRNAs or their target sites may cause the alteration of regulatory networks and serious phenotype changes. In this study, we proposed a novel approach to construct a miRNA-miRNA crosstalk network in Arabidopsis thaliana based on the notion that two cooperative miRNAs toward common targets are under a strong pressure to be inherited together across ecotypes. By performing a genome-wide scan of the SNPs within the mature miRNAs and their target sites, we defined a "regulation fate profile" to describe a miRNA-target regulation being static (kept) or dynamic (gained or lost) across 1,135 ecotypes compared with the reference genome of Col-0. The cooperative miRNA pairs were identified by estimating the similarity of their regulation fate profiles toward the common targets. The reliability of the cooperative miRNA pairs was supported by solid expressional correlation, high PPImiRFS scores, and similar stress responses. Different combinations of static and dynamic miRNA-target regulations account for the cooperative miRNA pairs acting on various biological characteristics of miRNA conservation, expression, homology, and stress response. Interestingly, the targets that are co-regulated dynamically by both cooperative miRNAs are more likely to be responsive to stress. Hence, stress-related genes probably bear selective pressures in a certain group of ecotypes, in which miRNA regulations on the stress genes reprogram. Finally, three case studies showed that reprogramming miRNA-miRNA crosstalk toward the targets in specific ecotypes was associated with these ecotypes' climatic variables and geographical locations. Our study highlights the potential of miRNA-miRNA crosstalk as a genetic basis underlying environmental adaptation in natural populations.

Fusobacterium necrophorum Promotes Apoptosis and Inflammatory Cytokine Production Through the Activation of NF-κB and Death Receptor Signaling Pathways.

Fusobacterium necrophorum can cause liver abscess, foot rot in ruminants, and Lemire syndrome in humans, Also, its virulence factors can induce the apoptosis of macrophages and neutrophils. However, the detailed mechanism has not been fully clarified. This study investigated the mechanisms of apoptosis and inflammatory factor production in F. necrophorum-induced neutrophils and macrophages (RAW246.7). After infection of macrophages with F. necrophorum, 5-ethynyl-2'-deoxyuridine labeling assays indicated that F. necrophorum inhibited macrophage proliferation in a time- and dose-dependent manner. Hoechst staining and DNA ladder assays showed significant condensation of the nucleus and fragmentation of genomic DNA in F. necrophorum-infected macrophages, Annexin V (FITC) and propidium iodide (PI) assay confirmed the emergence of apoptosis in the macrophages and sheep neutrophils with F. necrophorum compared with the control. The group with significant apoptosis was subjected to RNA sequencing (RNA-Seq), and the sequencing results revealed 2581 up- and 2907 downregulated genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis of the differentially expressed genes showed that F. necrophorum drove apoptosis and production of inflammatory factors by activating genes related to the Nuclear Factor-κB (NF-κB) and death receptor pathways. Meanwhile, quantitative reverse transcription PCR and Western blot validation results were consistent with the results of transcriptome sequencing analysis. In conclusion, F. necrophorum induced apoptosis and production of pro-inflammatory factors through the NF-κB and death receptor signaling pathway, providing a theoretical basis for further mechanistic studies on the prevention and control of F. necrophorum disease treatment.

First description of the mitogenome and phylogeny:Aedes vexansand Ochlerotatus caspius of the Tribe Aedini (Diptera: Culicidae).

Culicidae, the mosquito family, includes more than 3600 species subdivided into the subfamilies Anophelinae and Culicinae. One-third of mosquitoes belong to the Aedini tribe, which is subordinate to the subfamily Culicinae, which comprises common vectors of viral zoonoses. The tribe of Aedini is extremely diverse in morphology and geographical distribution and has high ecological and medical significance. However, knowledge about the systematics of the Aedini tribe is still limited owing to its large population and the similar morphological characteristics of its species. This study provides the first description of the complete mitochondrial (mt) genome sequence of Aedes vexans and Ochlerotatus caspius belonging to the Aedini tribe. The mt genomes of A. vexans and O. caspius are circular molecules that are 15,861 bp and 15,954 bp in size, with AT contents of 78.54% and 79.36%, respectively. Both the circular mt genomes comprise 37 functional subunits, including 13 protein-coding genes (PCGs), two ribosomal RNA genes, 22 transfer RNA genes (tRNAs), and a control region (also known as the AT-rich region). The most common start codons are ATT/ATG, apart from cox1 (TCG) and nad5 (GTG), while TAA is the termination codon for all PCGs. All tRNAs have a typical clover leaf structure, except tRNA Ser1. Phylogenetic analysis of the concatenated, aligned amino acid sequences of the 13 PCGs showed that A. vexans gathered with Aedes sp. in a sister taxon, and O. caspius gathered with Ochlerotatus sp. in a sister taxon. The findings from the present study support the concept of monophyly of all groups, ratify the current taxonomic classification, and provide vital molecular marker resources for further studies of the taxonomy, population genetics, and systematics of the Aedini tribe.

Clinical characteristics of female patients diagnosed with congenital adrenal hyperplasia and plastic-esthetic related thoughts: a retrospective study.

OBJECTIVES: Congenital adrenal hyperplasia (CAH) is a rare disorder that can cause masculinization of the external genitalia in females, usually evident in neonates. To present a case series of female patients with CAH by summarizing their clinical features and outcomes. DESIGN: This retrospective study analyzed the clinical data of female patients with CAH admitted to the First Affiliated Hospital of Xiamen University from 1995 to 2019. MATERIALS AND METHODS: Clinical characteristics, CAH subtype, treatments, and outcomes were summarized from the medical records and analyzed. Follow-up was conducted after drug therapy and surgical treatment and was censored in 2019. RESULTS: Twenty-one female patients were diagnosed with CAH: 21-hydroxylase deficiency (21-OHD) in 17 patients and 17α-hydroxylase deficiency (17α-OHD) in four patients. The clinical manifestations of 21-OHD were clitoral hypertrophy, pigmentation, male secondary sexual development, genital malformation, sexual precocity, nausea, and vomiting. The clinical manifestations of 17α-OHD were hypertension, feminization, sexual infantilism, and pigmentation. The patients received hormone replacement therapy. When necessary, some patients underwent external genital organ orthomorphia or artificial periodic therapy. Twelve patients were followed up; their sexual development was improved, but seven patients had poor breast development due to late diagnosis and/or poor hormone treatment adherence. CONCLUSION: Female CAH patients are subject to genital deformities, virilizing signs, breast dysplasia, and other appearance defects. The purpose of this report is to improve plastic and esthetic surgeons' understanding of CAH.

Evaluation of Immunoprotective Effects of Fusobacterium necrophorum Outer Membrane Proteins 43K OMP, Leukotoxin and Hemolysin Multi-Component Recombinant Subunit Vaccine in Mice.

We evaluated the efficacy of three vaccine formulations containing different combinations of proteins (43K OMP, leukotoxin recombinant protein PL4 and hemolysin recombinant protein H2) and killed whole cell Fusobacterium necrophorum in preventing liver abscess. Four subcutaneous vaccines were formulated: vaccine 1 (43K OMP), vaccine 2 (PL4 and H2), vaccine 3 (43K OMP, PL4 and H2), and vaccine 4 (killed whole bacterial cell). 43K OMP, PL4, and H2 proteins were produced by using recombinant protein expression. To evaluate vaccine efficacy, we randomly allocated 50 BALB/c female mice to one of five different treatment groups: PBS control group, vaccine 1, vaccine 2, vaccine 3, and vaccine 4. Mice were vaccinated three times, with 14 days between each immunization. After immunization, the mice were challenged with F. necrophorum. The three key findings of this study are as follows: (1) Vaccine 3 has enabled mice to produce higher antibody titer following bacterial challenge, (2) in the liver pathology of mice, the vaccine 3 liver showed the least pathology, and (3) all four vaccines produced high levels of antibodies and cytokines in mice, but the level of vaccine 3 was the highest. Based on our results, it has been demonstrated that a mixture of F. necrophorum 43K OMP, PL4, and H2 proteins inoculated with mice can achieve protection against liver abscess in mice. Our research may therefore provide the basis for the development of a vaccine against F. necrophorum bovine infections.

Long non-coding RNA SOX21-AS1 modulates lung cancer progress upon microRNA miR-24-3p/PIM2 axis.

Lung cancer is a lethal cancer that threatens human health. Several studies have demonstrated the role of long non-coding RNAs (lncRNAs) in lung cancer. SOX21-AS1 is a newly discovered oncogenic lncRNA, but its molecular mechanism in lung cancer is not known. Here, the levels of SOX21-AS1, miR-24-3p, and PIM2 were examined in lung cancer and normal tissues. The relationships between miR-24-3p and SOX21-AS1 or PIM2 were predicted using bioinformatics tools and confirmed using a luciferase reporter assays. Colony formation, MTT, flow cytometry, and transwell assays were conducted to analyze cell proliferation, apoptosis, migration, and invasion abilities, respectively. Western blotting was used to measure PIM2 expression levels in cancer tissues and cells. SOX21-AS1 expression levels were high in lung cancer tissues and cells. In contrast, the amount of miR-24-3p bound to SOX21-AS1 was relatively low in cancerous tissues and cells. The knockdown of SOX21-AS1 decreased cell proliferation, activated apoptosis, and promoted cell migration and invasion. These effects were abolished by miR-24-3p inhibition. The oncogenic function of SOX21-AS1 mediated through targeting miR-24-3p was also demonstrated in animal models. PIM2 was targeted by miR-24-3p and showed increased levels in tumor tissues and cells. Furthermore, miR-24-3p overexpression inhibited the proliferation and promoted the apoptosis of lung cancer cells. In lung cancer cells, SOX21-AS1 negatively modulated the miR-24-3p/PIM2 axis to facilitate their proliferation, migration, and invasion. These findings offer a novel idea for future research on treating lung cancer at the molecular level.

The distributions of 134Cs, 137Cs and 90Sr in the northwest Pacific seawater in the winter of 2012.

To understand the status of the radionuclides released during the Fukushima Dai-ichi Nuclear Power Plant accident, the 134Cs, 137Cs and 90Sr in the seawater in the public area of the northwest Pacific Ocean were analyzed in November-December 2012. The radioactivity of 134Cs, 137Cs and 90Sr decreased sharply from June 2011 to November-December 2012. The highest average values of 134Cs and 137Cs were found at a depth of 500 m, suggesting that 134Cs and 137Cs had been transported to a depth of 500 m or deeper by the end of 2012. Total inventories of 0.80 ± 0.20 pBq for 137Cs from the surface to a depth of 500 m and 0.07 ± 0.02 pBq for 90Sr from the surface to a depth of 100 m were obtained in the waters southeast of Fukushima. 134Cs was detectable in the Chinese exclusive economic zone, and the seawater quality was much lower than the target level for China.

Combination therapy of gefitinib and miR-30a-5p may overcome acquired drug resistance through regulating the PI3K/AKT pathway in non-small cell lung cancer.

BACKGROUND: Non-small cell lung cancer (NSCLC) patients with an epidermal growth factor receptor (EGFR) mutation often initially respond to EGFR tyrosine kinase inhibitor (EGFR-TKI) treatment but may acquire drug resistance due to multiple factors. MicroRNAs are a class of small noncoding and endogenous RNA molecules that may play a role in overcoming the resistance. MATERIALS AND METHODS: In this study, we explored and validated, through in vitro experiments and in vivo models, the ability of a combination treatment of EGFR-TKI, namely gefitinib, and a microRNA mimic, miR-30a-5p, to overcome drug resistance through regulation of the insulin-like growth factor receptor-1 (IGF1R) and hepatocyte growth factor receptor signaling pathways, which all converge on phosphatidylinositol 3 kinase (PI3K), in NSCLC. First, we examined the hypothesized mechanisms of drug resistance in H1650, H1650-acquired gefitinib-resistance (H1650GR), H1975, and H460 cell lines. Next, we investigated a potential combination treatment approach to overcome acquired drug resistance in the H1650GR cell line and an H1650GR cell implanted mouse model. RESULTS: Dual inhibitors of EGFR and IGF1R significantly lowered the expression levels of phosphorylated protein kinase B (p-AKT) and phosphorylated mitogen-activated protein kinase (p-ERK) compared with the control group in all cell lines. With the ability to repress PI3K expression, miR-30a-5p mimics induced cell apoptosis, and inhibited cell invasion and migration in the treated H1650GR cell line. CONCLUSION: Gefitinib, combined with miR-30a-5p mimics, effectively suppressed the growth of H1650GR-induced tumor in xenografts. Hence, a combination therapy of gefitinib and miR-30a-5p may play a critical role in overcoming acquired resistance to EGFR-TKIs. The reviews of this paper are available via the supplemental material section.