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© 2014 Baccarella et al.; licensee BioMed Central Ltd.Background: Malaria, caused by Plasmodium sp. parasites, is a leading cause of global morbidity and mortality. Cerebral malaria, characterized by neurological symptoms, is a life-threatening complicatio

Background: Long noncoding RNAs (lncRNAs) play a critical role in gastric cancer (GC) progression and metastasis. However, research comprehensively exploring tissue-derived lncRNAs for predicting peritoneal recurrence in patients with GC remains limited. This study aims to investigate the transcriptional landscape of lncRNAs in GC with peritoneal metastasis (PM) and to develop an integrated lncRNA-based score to predict peritoneal recurrence in patients with GC after radical gastrectomy., Methods: We analyzed the transcriptome profile of lncRNAs in paired peritoneal, primary gastric tumor, and normal tissue specimens from 12 patients with GC in the Sun Yat-sen University Cancer Center (SYSUCC) discovery cohort. Key lncRNAs were identified via interactive analysis with the TCGA database and SYSUCC validation cohort. A score model was constructed using the LASSO regression model and nomogram COX regression and evaluated using receiver operating characteristic curves. The role of lncRNAs in the PM of GC was then examined through wound healing, Transwell, 3D multicellular tumor spheroid invasion, and peritoneal cavity xenograft tumorigenicity assays in mice., Result: Five essential lncRNAs were screened and incorporated into the PM risk score to predict peritoneal recurrence-free survival (pRFS). We developed a comprehensive, integrated nomogram score, including the PM risk score, pT, pN, and tumor size, which could effectively predict the 5-year pRFS with an Area under the curve of 0.79 (95% CI: 0.71-0.88). Subsequently, we demonstrated that one of these lncRNAs, CASC15, promoted the invasion and migration of GC cells in vitro and facilitated the PM of GC cells in vivo, initially verifying that lncRNAs contribute to the PM of GC. Mechanistic analysis demonstrated that CASC15 promoted EMT and metastasis by activating the JNK and p38 pathways., Conclusion: A lncRNA-based integrated score was constructed in this study to predict peritoneal recurrence in patients clinically., Competing Interests: Declarations. Ethics approval and consent to participate: This study was conducted in accordance with the Declaration of Helsinki. The study was approved by the Institutional Review Board (IRB) of Sun Yat-Sen University Cancer Center (SYSUCC, Guangzhou, China) with the IRB number of G2021-036. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ostreid herpesvirus 1 (OsHV-1), a member of the family Malacoherpesviridae (order Herpesvirales ), is a major pathogen of bivalves. However, the molecular details of the malacoherpesvirus infection cycle and its overall similarity to the replication of mammalian herpesviruses (family Orthoherpesviridae ) remain obscure. Here, to gain insights into the OsHV-1 biology, we performed long-read sequencing of infected blood clams, Anadara broughtonii , which yielded over one million OsHV-1 long reads. These data enabled the annotation of the viral genome with 78 gene units and 274 transcripts, of which 67 were polycistronic mRNAs, 35 ncRNAs, and 20 natural antisense transcripts (NATs). Transcriptomics and proteomics data indicate preferential transcription and independent translation of the capsid scaffold protein as an OsHV-1 capsid maturation protease isoform. The conservation of this transcriptional architecture across Herpesvirales likely indicates its functional importance and ancient origin. Moreover, we traced RNA editing events using short-read sequencing and supported the presence of inosine nucleotides in native OsHV-1 RNA, consistent with the activity of adenosine deaminase acting on dsRNA 1 (ADAR1). Our data suggest that, whereas RNA hyper-editing is concentrated in specific regions of the OsHV-1 genome, single-nucleotide editing is more dispersed along the OsHV-1 transcripts. In conclusion, we reveal the existence of conserved pan- Herpesvirales transcriptomic architecture of the capsid maturation module and uncover a transcription-based viral counter defence mechanism, which presumably facilitates the evasion of the host ADAR antiviral system., Competing Interests: None declared., (© The Author(s) 2024. Published by Oxford University Press.)

OsHV-1 caused detrimental infections in a variety of bivalve species of major importance to aquaculture worldwide. Since 2012, there has been a notable increase in the frequency of mass mortality events of the blood clam associated with OsHV-1 infection. The pathological characteristics, tissue and cellular tropisms of OsHV-1 in A. broughtonii remain unknown. In this study, we sought to investigate the distribution of OsHV-1 in five different organs (mantle, hepatopancreas, gill, foot, and adductor muscle) of A. broughtonii by quantitative PCR, histopathology and in situ hybridization (ISH), to obtain insight into the progression of the viral infection. Our results indicated a continuous increase in viral loads with the progression of OsHV-1 infection, reaching a peak at 48 h or 72 h post-infection according to different tissues. Tissue damage and necrosis, as well as colocalized OsHV-1 ISH signals, were observed primarily in the connective tissues of various organs and gills. Additionally, minor tissue damage accompanied by relatively weak ISH signals was detected in the foot and adductor muscle, which were filled with muscle tissue. The predominant cell types labeled by ISH signals were infiltrated hemocytes, fibroblastic-like cells, and flat cells in the gill filaments. These results collectively illustrated the progressive alterations in pathological confusion and OsHV-1 distribution in A. broughtonii , which represent most of the possible responses of cells and tissues to the virus.

Roasting is necessary for bringing out the aroma and flavor of coffee beans, making coffee one of the most consumed beverages. However, this process also generates a series of toxic compounds, including acrylamide and furanic compounds (5-hydroxymethylfurfural, furan, 2-methylfuran, 3-methylfuran, 2,3-dimethylfuran, and 2,5-dimethylfuran). Furthermore, not much is known about the formation of these compounds in emerging coffee formulations containing alcohol and sugars. Therefore, this study investigated the effect of roasting time and degree on levels of acrylamide and furanic compounds in arabica coffee using fast and slow roasting methods. The fast and slow roasting methods took 5.62 min and 9.65 min, respectively, and reached a maximum of 210 °C to achieve a light roast. For the very dark roast, the coffee beans were roasted for 10.5 min and the maximum temperature reached 245 °C. Our findings showed that the levels of acrylamide (375 ± 2.52 μg kg -1 ) and 5-HMF (194 ± 11.7 mg kg -1 ) in the slow-roasted coffee were 35.0 % and 17.4 % lower than in fast-roasted coffee. Furthermore, light roast coffee had significantly lower concentrations of acrylamide and 5-HMF than very dark roast, with values of 93.7 ± 7.51 μg kg -1 and 21.3 ± 10.3 mg kg -1 , respectively. However, the levels of furan and alkylfurans increased with increasing roasting time and degree. In this study, we also examined the concentrations of these pollutants in new coffee formulations consisting of alcohol-, sugar-, and honey-infused coffee beans. Formulations with honey and sugar resulted in higher concentrations of 5-HMF, but no clear trend was observed for acrylamide. On the other hand, formulations with honey had higher concentrations of furan and alkylfurans. These results indicate that optimizing roasting time and temperature might not achieve the simultaneous reduction of all the pollutants. Additionally, sugar- and honey-infused coffee beans are bound to have higher furanic compounds, posing a higher health risk., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Cardiovascular diseases (CVDs) stand as a predominant global health concern, introducing vast socioeconomic challenges. In addressing this pressing dilemma, enhanced diagnostic modalities have become paramount, positioning electrochemical biosensing as an instrumental innovation. This comprehensive review navigates the multifaceted terrain of CVDs, elucidating their defining characteristics, clinical manifestations, therapeutic avenues, and intrinsic risk factors. Notable emphasis is placed on pivotal diagnostic tools, spotlighting cardiac biomarkers distinguished by their unmatched clinical precision in terms of relevance, sensitivity, and specificity. Highlighting the broader repercussions of CVDs, there emerges an accentuated need for refined diagnostic strategies. Such an exploration segues into a profound analysis of electrochemical biosensing, encapsulating its foundational principles, diverse classifications, and integral components, notably recognition molecules and transducers. Contemporary advancements in biosensing technologies are brought to the fore, emphasizing pioneering electrode architectures, cutting-edge signal amplification processes, and the synergistic integration of biosensors with microfluidic platforms. At the core of this discourse is the demonstrated proficiency of biosensors in detecting cardiovascular anomalies, underpinned by empirical case studies, systematic evaluations, and clinical insights. As the narrative unfolds, it addresses an array of inherent challenges, spanning intricate technicalities, real-world applicability constraints, and regulatory considerations, finally, by casting an anticipatory gaze upon the future of electrochemical biosensing, heralding a new era of diagnostic tools primed to revolutionize cardiovascular healthcare.

Precision measurements by the Alpha Magnetic Spectrometer (AMS) on the International Space Station of the deuteron (D) flux are presented. The measurements are based on 21×10^{6} D nuclei in the rigidity range from 1.9 to 21 GV collected from May 2011 to April 2021. We observe that over the entire rigidity range the D flux exhibits nearly identical time variations with the p, ^{3}He, and ^{4}He fluxes. Above 4.5 GV, the D/^{4}He flux ratio is time independent and its rigidity dependence is well described by a single power law ∝R^{Δ} with Δ_{D/^{4}He}=-0.108±0.005. This is in contrast with the ^{3}He/^{4}He flux ratio for which we find Δ_{^{3}He/^{4}He}=-0.289±0.003. Above ∼13  GV we find a nearly identical rigidity dependence of the D and p fluxes with a D/p flux ratio of 0.027±0.001. These unexpected observations indicate that cosmic deuterons have a sizable primarylike component. With a method independent of cosmic ray propagation, we obtain the primary component of the D flux equal to 9.4±0.5% of the ^{4}He flux and the secondary component of the D flux equal to 58±5% of the ^{3}He flux.

Two new triarylamine-based diamine monomers, namely, N , N '-bis(4-methoxyphenyl)- N , N '-bis(4-(4-aminophenyl-4'-methoxyphenylamino)phenyl)- p -phenylenediamine ( 3 ) and N , N '-bis(4-methoxyphenyl)- N , N '-bis(4-((4-aminophenyl-1-naphthyl)amino)phenyl)- p -phenylenediamine ( 7 ), were successfully synthesized and led to two series of electroactive polyamides by polycondensation reactions with common aromatic dicarboxylic acids. The polymers demonstrated multicolored electrochromism, high optical contrast, and remarkable enhancements in redox and electrochromic stability. Compared to other triarylamine-based polymers, the studied polyamides exhibited enhanced electrochromic stability (only 3~6% decay of its coloration efficiency at 445 nm after 14,000 switching cycles) at the first oxidation stage. The polyamides also showed strong absorption in the near-infrared region upon oxidation. Polymers with multicolored electrochromism and high redox stability can be developed by incorporation of four triarylamine cores in each repeat unit and electron-donating methoxy groups on the active sites of the triphenylamine units.

Tryptophan metabolites, such as 5-hydroxytryptophan (5-HTP), serotonin, and melatonin, hold significant promise as supplements for managing various mood-related disorders, including depression and insomnia. However, their chemical production via chemical synthesis and phytochemical extraction presents drawbacks, such as the generation of toxic byproducts and low yields. In this study, we explore an alternative approach utilizing S. cerevisiae STG S101 for biosynthesis. Through a series of eleven experiments employing different combinations of tryptophan supplementation, Tween 20, and HEPES buffer, we investigated the production of these indolamines. The tryptophan metabolites were analyzed using liquid chromatography with tandem mass spectrometry (LC-MS/MS). Notably, setups replacing peptone in the YPD media with tryptophan (Run 3) and incorporating tryptophan along with 25 mM HEPES buffer (Run 4) demonstrated successful biosynthesis of 5-HTP and serotonin. The highest 5-HTP and serotonin concentrations were 58.9 ± 16.0 mg L -1 and 0.0650 ± 0.00211 mg L -1 , respectively. Melatonin concentrations were undetected in all the setups. These findings underscore the potential of using probiotic yeast strains as a safer and conceivably more cost-effective alternative for indolamine synthesis. The utilization of probiotic strains presents a promising avenue, potentially offering scalability, sustainability, reduced environmental impact, and feasibility for large-scale production.

Mercury's neurotoxic effects have prompted the development of advanced control and remediation methods to meet stringent measures for industries with high-mercury feedstocks. Industries with significant Hg emissions, including artisanal and small-scale gold mining (ASGM)-789.2 Mg year -1 , coal combustion-564.1 Mg year -1 , waste combustion-316.1 Mg year -1 , cement production-224.5 Mg year -1 , and non-ferrous metals smelting-204.1 Mg year -1 , use oxidants and adsorbents capture Hg from waste streams. Oxidizing agents such as O 3 , Cl 2 , HCl, CaBr 2 , CaCl 2 , and NH 4 Cl oxidize Hg 0 to Hg 2+ for easier adsorption. To functionalize adsorbents, carbonaceous ones use S, SO 2 , and Na 2 S, metal-based adsorbents use dimercaprol, and polymer-based adsorbents are grafted with acrylonitrile and hydroxylamine hydrochloride. Adsorption capacities span 0.2-85.6 mg g -1 for carbonaceous, 0.5-14.8 mg g -1 for metal-based, and 168.1-1216 mg g -1 for polymer-based adsorbents. Assessing Hg contamination in soils and sediments uses bioindicators and stable isotopes. Remediation approaches include heat treatment, chemical stabilization and immobilization, and phytoremediation techniques when contamination exceeds thresholds. Achieving a substantially Hg-free ecosystem remains a formidable challenge, chiefly due to the ASGM industry, policy gaps, and Hg persistence. Nevertheless, improvements in adsorbent technologies hold potential., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 Published by Elsevier Ltd.)

Activated sludge (AS) plays a vital role in removing organic pollutants and nutrients from wastewater. However, the risks posed by horizontal gene transfer (HGT) between bacteria in AS are still unclear. Here, a total of 478 high-quality non-redundant metagenome-assembled genomes (MAGs) were obtained. >50 % and 5 % of MAGs were involved in at least one HGT and recent HGT, respectively. Most of the transfers (82.4 %) of antimicrobial resistance genes (ARGs) occurred among the classes of Alphaproteobacteria and Gammaproteobacteria. The bacteria involved in the transfers of virulence factor genes (VFGs) mainly include Alphaproteobacteria (42.3 %), Bacteroidia (19.2 %), and Gammaproteobacteria (11.5 %). Moreover, the number of ARGs and VFGs in the classes of Alphaproteobacteria and Gammaproteobacteria was higher than that in other bacteria (P < 0.001). Mobile genetic elements were important contributors to ARGs and VFGs in AS bacteria. These results have implications for the management of antimicrobial resistance and virulence in activated sludge microorganisms., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

The present letter to the editor is related to the study titled ' Angiotensin-converting enzyme 2 improves liver fibrosis in mice by regulating autophagy of hepatic stellate cells'. Angiotensin-converting enzyme 2 can alleviate liver fibrosis by regulating autophagy of hepatic stellate cells and affecting the renin-angiotensin system., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Perkinsosis has been recognized as one of the major threats to natural and farmed bivalve populations, many of which are of commercial as well as environmental significance. Three Perkinsus species have been identified in China, and the Manila clam (Ruditapes philippinarum) was the most frequently infected species in northern China. Although the occurrence and seasonal variation of Perkinsus spp. have previously been examined, the pathological characteristics of these infections in wild Manila clams and sympatric species in China have seldom been reported. In the present study, the prevalence and intensity of Perkinsus infection in wild populations of Manila clams and 10 sympatric species from three sites were investigated by Ray's fluid thioglycolate medium (RFTM) assay seasonally across a single year. Perkinsus infection was only identified in Manila clams, with a high prevalence (274/284 = 96.48 %) and low intensity (89.8 % with a Mackin value ≤ 2, suggesting generally low-intensity infections) throughout the year. Heavily infected clams were mainly identified in Tianheng in January, which displayed no macroscopic signs of disease. An overview of the whole visceral mass section showed that the trophozoites mostly aggregated in gills and connective tissue of the digestive tract, to a lesser extent in the mantle and foot, and even less frequently in adductor muscle and connective tissues of the gonad. PCR and ITS-5.8S rRNA sequencing of 93 representative RFTM-positive samples revealed a 99.69 to 100 % DNA sequence identity to Perkinsus olseni. Unexpectedly, significantly higher infection intensities were usually identified in January and April when the Condition Index (CI) was relatively high. We propose that factors associated with the anthropogenic harvesting pressure and irregular disturbances should be responsible for the uncommon seasonal infection dynamics of perkinsosis observed in the present study., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The Pacific oyster Crassostrea gigas is one of the most important cultured marine species around the world. Production of Pacific oysters in China has depended primarily on hatchery produced seeds since 2016, with the successful introduction and development of triploid oysters. However, the seed supply of Pacific oysters is threatened by recurring mass mortality events in recent years. Vibriosis is the most commonly encountered disease associated with intensive oyster culture in hatcheries and nurseries. Vibrio alginolyticus and Bacillus hwajinpoensis were the two strains with pathogenic and probiotic effects, respectively, identified during the Pacific oyster larvae production. To monitor their colonization process in Pacific oyster larvae, green fluorescent protein (GFP) and red fluorescent protein (RFP) were labeled to the pathogenic V. alginolyticus and the probiotic B. hwajinpoensis stain, respectively. The pathogenic and probiotic effects of the two strains during the colonization process were then assessed. Stabile expression of GFP and RFP were observed in corresponding stains, and the capabilities of growth, biofilm formation and in vitro adhesion of GFP- and RFP- tagged stains were not significantly different from those of the wild-type strains. Usage of probiotics of 10 5 CFU/mL significantly inhibited the growth of pathogenic V. alginolyticus and reduced the mortality of D-sharped larvae. Both the pathogenic and probiotic strains employed a similar route to enter and colonize the oyster larvae, which indicates that competing with pathogens for binding and spreading sites were one of the mechanisms of B. hwajinpoensis to provide the probiotic effects to oyster larvae. In summary, employment of fluorescence-tagged pathogenic and probiotic strains simultaneously provides us with an excellent bioassay model to investigate the potential mechanisms of probiotics., Competing Interests: The authors declare no conflicts of interest.

A vinylogous addition reaction of allyl aryl ketones with good yields and excellent regioselectivity catalyzed by squaramide catalysts has been developed. A series of chiral tertiary alcohols and bicyclic pyrrolidones could be synthesized in good to excellent yields, enantioselectivities, and diaseteroselectivities. Both experimental results and DFT calculations indicate that 1,2-addition reaction is favorable when the reaction is employed at a lower temperature, while the 1,4-addition/cyclization pathway is favorable when the reaction is employed at a higher temperature. Furthermore, the formation of compound 4 can potentially arise from either the 1,4-addition/cyclization pathway or retro-aldol reaction of compound 3 , followed by subsequent 1,4-addition/cyclization.

Vibrio parahaemolyticus is a common pathogen, and has emerged with multiple antimicrobial resistance (AMR). However, few studies have conducted large-scale investigations of AMR and virulence trends of V. parahaemolyticus worldwide. This study longitudinally monitored antibiotic resistance genes (ARGs) and virulence factor genes (VFGs) trends of 1540 V. parahaemolyticus isolates isolated from 1951 to 2021. The number of ARGs in V. parahaemolyticus isolates distinctly increased over the years (P = 5.9e-10), while the number of VFGs decreased significantly (P < 2.2e-16). However, the number of VFGs of isolates isolated from humans has not changed significantly over the years (R = 0.013, P = 0.74), suggesting that the pathogenic risk to humans has not been reduced. Besides, mobile genetic elements are important contributors to ARGs in V. parahaemolyticus (R = 0.34, P < 2.2e-16), but have no promoting effect on VFGs (P = 0.50). The structural equation model illustrated that the human development index promoted the consumption of antibiotics, thereby indirectly promoting an increase in the AMR of the V. parahaemolyticus isolates. Finally, the random forest was performed to predict the ARG and VFG risks of global terrestrial V. parahaemolyticus isolates, and successfully map these threats with over 80% accuracy. This study aimed to evaluate the global risks posed by AMR and virulence, which helps to develop methods specifically targeting V. parahaemolyticus to mitigate these threats., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

We present the precision measurements of 11 years of daily cosmic positron fluxes in the rigidity range from 1.00 to 41.9 GV based on 3.4×10^{6} positrons collected with the Alpha Magnetic Spectrometer (AMS) aboard the International Space Station. The positron fluxes show distinctly different time variations from the electron fluxes at short and long timescales. A hysteresis between the electron fluxes and the positron fluxes is observed with a significance greater than 5σ at rigidities below 8.5 GV. On the contrary, the positron fluxes and the proton fluxes show similar time variation. Remarkably, we found that positron fluxes are modulated more than proton fluxes with a significance greater than 5σ for rigidities below 7 GV. These continuous daily positron fluxes, together with AMS daily electron, proton, and helium fluxes over an 11-year solar cycle, provide unique input to the understanding of both the charge-sign and mass dependencies of cosmic rays in the heliosphere.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Introduction: This study aimed to investigate the presentations and survival outcomes of the distant metastatic non-small cell lung cancer (NSCLC) without lymph node involvement to obtain a clearer picture of this special subgroup of metastatic NSCLC., Method: A least absolute shrinkage and selection operator (LASSO) penalized Cox regression analysis was used to select the prognostic variables. A nomogram and corresponding risk-classifying systems were constructed. The C-index and calibration curves were used to evaluate the performance of the model. Overall survival (OS) curves were plotted using the Kaplan-Meier method, and the log-rank test was used to compare OS differences between groups. Propensity score matching (PSM) was performed to reduce bias., Result: A total of 12 610 NSCLC patients with M1 category (N0 group: 3045 cases; N1-3 group: 9565 cases) were included. Regarding the N0 group, multivariate analysis demonstrated that age, sex, race, surgery, grade, tumor size, and M category were independent prognostic factors. A nomogram and corresponding risk-classifying systems were formulated. Favorable validation results were obtained from the C-index, calibration curves, and survival comparisons. Survival curves demonstrated that N0 NSCLC patients had better survival than N1-3 NSCLC patients both before and after PSM. Furthermore, the survival of resected N0M1 patients was superior to that of those without surgery., Conclusion: In this study, a prognostic nomogram and risk-classifying systems designed for the T1-4N0M1 NSCLC patients showed acceptable performance. Primary lung tumor resection might be a feasible treatment for this population subset. Additionally, we proposed that lymph node stage might have a place in the forthcoming tumor-node-metastasis (TNM) staging proposal for NSCLC patients with M1 category., (© 2023 The Authors. The Clinical Respiratory Journal published by John Wiley & Sons Ltd.)

Purpose: Revision bariatric surgery may be undertaken after weight loss failure and/or complications following primary bariatric surgery. This study aims to compare the efficacy and safety of revision laparoscopic sleeve gastrectomy (RLSG) after gastric banding (GB) to those of primary laparoscopic sleeve gastrectomy (PLSG)., Materials and Methods: A retrospective, propensity-score matched study was conducted to compare between PLSG (control) patients and RLSG after GB (treatment) patients. Patients were matched using 2:1 nearest neighbor propensity score matching without replacement. Patients were compared on weight loss outcomes and postoperative complications for up to five years., Results: 144 PLSG patients were compared against 72 RLSG patients. At 36 months, PLSG patients had significantly higher mean %TWL than RLSG patients (27.4 ± 8.6 [9.3-48.9]% vs. 17.9 ± 10.2 [1.7-36.3]%, p < 0.01). At 60 months, both groups had similar mean %TWL (16.6 ± 8.1 [4.6-31.3]% vs. 16.2 ± 6.0 [8.8-22.4)]%, p > 0.05). Early functional complication rates were slightly higher with PLSG (13.9% vs. 9.7%), but late functional complication rates were comparatively higher with RLSG (50.0% vs. 37.5%). The differences were not statistically significant (p > 0.05). Both early (0.7% vs 4.2%) and late (3.5% vs 8.3%) surgical complication rates were lower in PLSG patients compared to RLSG patients but did not reach statistical significance (p > 0.05)., Conclusion: RLSG after GB has poorer weight loss outcomes than PLSG in the short-term. Although RLSG may carry higher risks of functional complications, the safety of RLSG and PLSG are overall comparable., (© 2023. The Author(s).)

In this study, we developed an organocatalyst-controlled site-selectivity switchable Friedel-Crafts reaction of 1-naphthols and 2,3-dioxopyrrolidines. The o -selective Friedel-Crafts reaction was achieved with chiral tertiary amines, while the p -selective Friedel-Crafts reaction was accomplished with Brønsted acids or Lewis acids. With this protocol, a range of functionalized polycyclic 2-pyrrolidinone derivatives were prepared. Moreover, theoretical mechanistic investigations provided insights into the site-selectivity reaction pathway and the origin of chiral induction for the o -selective Friedel-Crafts reaction.

We report the properties of primary cosmic-ray sulfur (S) in the rigidity range 2.15 GV to 3.0 TV based on 0.38×10^{6} sulfur nuclei collected by the Alpha Magnetic Spectrometer experiment (AMS). We observed that above 90 GV the rigidity dependence of the S flux is identical to the rigidity dependence of Ne-Mg-Si fluxes, which is different from the rigidity dependence of the He-C-O-Fe fluxes. We found that, similar to N, Na, and Al cosmic rays, over the entire rigidity range, the traditional primary cosmic rays S, Ne, Mg, and C all have sizeable secondary components, and the S, Ne, and Mg fluxes are well described by the weighted sum of the primary silicon flux and the secondary fluorine flux, and the C flux is well described by the weighted sum of the primary oxygen flux and the secondary boron flux. The primary and secondary contributions of the traditional primary cosmic-ray fluxes of C, Ne, Mg, and S (even Z elements) are distinctly different from the primary and secondary contributions of the N, Na, and Al (odd Z elements) fluxes. The abundance ratio at the source for S/Si is 0.167±0.006, for Ne/Si is 0.833±0.025, for Mg/Si is 0.994±0.029, and for C/O is 0.836±0.025. These values are determined independent of cosmic-ray propagation.

The Pacific oyster ( Crassostrea gigas ) aquaculture industry increased rapidly in China with the introduction and promotion of triploid oysters in recent years. Mass mortalities affecting different life stages of Pacific oysters emerged periodically in several important production areas of Northern China. During 2020 and 2021, we conducted a passive two-year investigation of infectious pathogens linked to mass mortality. Ostreid herpesvirus-1 (OsHV-1) was detected to be associated with mass mortalities of hatchery larvae, but not juveniles and adults in the open sea. Protozoan parasites, such as Marteilia spp., Perkinsus spp. and Bonamia spp. were not detected. Bacterial isolation and identification revealed that Vibrio natriegens and Vibrio alginolyticus were the most frequently (9 out of 13) identified two dominant bacteria associated with mass mortalities. Pseudoalteromonas spp. was identified as the dominant bacteria in three mortality events that occurred during the cold season. Further bacteriological analysis was conducted on two representative isolates of V. natriegens and V. alginolyticus , designated as CgA1-1 and CgA1-2. Multisequence analysis (MLSA) showed that CgA1-1 and CgA1-2 were closely related to each other and nested within the Harveyi clade. Bacteriological investigation revealed faster growth, and more remarkable haemolytic activity and siderophore production capacity at 25 °C than at 15 °C for both CgA1-1 and CgA1-2. The accumulative mortalities of experimental immersion infections were also higher at 25 °C (90% and 63.33%) than at 15 °C (43.33% and 33.33%) using both CgA1-1 and CgA1-2, respectively. Similar clinical and pathological features were identified in samples collected during both naturally and experimentally occurring mortalities, such as thin visceral mass, discolouration, and connective tissue and digestive tube lesions. The results presented here highlight the potential risk of OsHV-1 to hatchery production of larvae, and the pathogenic role of V. natriegens and V. alginolyticus during mass mortalities of all life stages of Pacific oysters in Northern China.

Background: The pineal tumor was once considered as a restricted area for surgery. Such cases are rare, with many different opinions on surgical treatment. This study aimed to review our experience of tumor treatment in the pineal region and explore the optimal treatment strategy., Methods: The clinical data of 72 patients with pineal tumors from January 1997 to May 2015 (18 years) were retrospectively analyzed. Preoperative preparation, pathology type, tumor resection rate, surgical approach, and follow-up outcomes were used as the indicators to evaluate the treatment efficacy., Results: The Krause approach was used in 46 cases, the Poppen approach in 10 cases, and the transcallosal-lateral ventricle-choroid fissure approach in 16 cases. The postoperative pathological results were as follows: 24 cases of germinoma, 11 of teratoma, 15 of glioma, 6 of meningioma, 11 of Pineocytoma, 2 of cholesteatoma, 2 of cavernous hemangioma, and 1 of choriocarcinoma. Further, the study included 64 cases of total surgical resections, 8 of subtotal resections, and 2 deaths. The follow-up period was from 7 months to 10 years. Further, 51 (70.8%) patients were followed up. The multivariate regression model showed that the surgical method and the pathological type contributed significantly to predicting outcomes., Conclusions: The type of pathology, extent of excision, and surgical approach had a significant impact on the prognosis of patients. The transcallosal-lateral ventricle-choroid fissure approach for large and medium-sized pineal tumors near the posterior part of the third ventricle had good efficacy., (Copyright © 2022. Published by Elsevier Inc.)

Shigella flexneri infection is the main cause of diarrhea in humans worldwide. The emergence of antimicrobial resistance (AMR) of S. flexneri is a growing public health threat worldwide, while large-scale studies monitoring the longitudinal AMR trends of isolates remain scarce. Here, the AMR gene (ARG) profiles of 717 S. flexneri isolates from 1920 to 2020 worldwide were determined. The results showed that the average number of ARGs in isolates has increased significantly, from 19.2 ± 2.4 before 1970 to 29.6 ± 5.3 after 2010. In addition, mobile genetic elements were important contributors to ARGs in S. flexneri isolates. The results of the structural equation model showed that the human development index drove the consumption of antibiotics and indirectly promoted the antibiotic resistance. Finally, a machine learning algorithm was used to predict the antibiotic resistance risk of global terrestrial S. flexneri isolates and successfully map the antibiotic resistance threats in global land habitats with over 80% accuracy. Collectively, this study monitored the longitudinal AMR trends, quantitatively surveilled the health risk of S. flexneri AMR, and provided a theoretical basis for mitigating the threat of antibiotic resistance.

In this work, staggered bottom-gate structure amorphous In-Ga-Zn-O (a-IGZO) thin film transistors (TFTs) with high-k ZrO 2 gate dielectric were fabricated using low-cost atmospheric pressure-plasma enhanced chemical vapor deposition (AP-PECVD) with in situ hydrogenation to modulate the carrier concentration and improve interface quality. Subsequently, a neutral oxygen beam irradiation (NOBI) technique is applied, demonstrating that a suitable NOBI treatment could successfully enhance electrical characteristics by reducing native defect states and minimize the trap density in the back channel. A reverse retrograde channel (RRGC) with ultra-high/low carrier concentration is also formed to prevent undesired off-state leakage current and achieve a very low subthreshold swing. The resulting a-IGZO TFTs exhibit excellent electrical characteristics, including a low subthreshold swing of 72 mV dec -1 and high field-effect mobility of 35 cm 2 V -1 s -1 , due to conduction path passivation and stronger carrier confinement in the RRGC. The UV-vis spectroscopy shows optical transmittance above 90% in the visible range of the electromagnetic spectrum. The study confirms the H 2 plasma with NOBI-treated a-IGZO/ZrO 2 TFT is a promising candidate for transparent electronic device applications., (© 2023 IOP Publishing Ltd.)

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused significant challenges for adolescent mental health., Aim: To survey adolescent students in China to determine the effects of the COVID-19 pandemic on their mental health., Methods: A multicenter cross-sectional comparative investigation was conducted in March 2022. We collected demographic information and survey data related to the COVID-19 pandemic. The Patient Health Questionnaire-9 and Generalized Anxiety Disorder Screener scales were used for objective assessment of depression and anxiety., Results: We collected mental health questionnaires from 3184 students. The investigation demonstrated that adolescents most strongly agreed with the following items: Increased time spent with parents, interference with academic performance, and less travel. Conversely, adolescents most strongly disagreed with the following items: Not having to go to school, feeling an increase in homework, and not socializing with people; 34.6% of adolescents were depressed before COVID-19, of which 1.9% were severely depressed. After COVID-19, 26.3% of adolescents were prone to depression, of which 1.4% were severely depressed. 24.4% of adolescents had anxiety before COVID-19, with severe anxiety accounting for 1.6%. After COVID-19, 23.5% of adolescents were prone to anxiety, of which 1.7% had severe anxiety., Conclusion: Chinese adolescents in different grades exhibited different psychological characteristics, and their levels of anxiety and depression were improved after the COVID-19 pandemic. Changes in educational management practices since the COVID-19 pandemic may be worth learning from and optimizing in long-term educational planning., Competing Interests: Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article., (©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.)

Two reagent-controlled regiodivergent annulation protocols for Achmatowicz products with vinylogous nucleophiles have been developed, which furnished a series of bicyclic cyclopenta[ b ]pyrans and 8-oxabicyclo[3.2.1]octane derivatives in 28-90% yields. Plausible mechanisms were proposed to involve either Pd-catalyzed Tsuji-Trost allyl-allyl coupling and concomitant Michael cyclization or quinine-promoted cascade stepwise [5 + 2] cycloaddition and intramolecular Michael cyclization.

Background: Postoperative pancreatic fistula (POPF) remains the primary complication of distal pancreatectomies. We aimed to review whether staple line reinforcement with continuous lockstitches would lead to decreased grade B and C pancreatic fistula in patients undergoing distal pancreatectomy., Methods: This retrospective study enrolled consecutive patients scheduled to undergo distal pancreatectomy at a large tertiary hospital. A comparison was conducted between lockstitch reinforcement and non-reinforcement for remnant closure during distal pancreatectomies from August 2016 to February 2021. Propensity score matching was applied to balance the two groups with covariates including abdominal and back pain, diabetes mellitus, and estimated blood loss. The primary outcome was POPF rate., Results: A total of 153 patients were enrolled in the study (89 lockstitch reinforcements, 64 non-reinforcements), of whom 128 patients (64 per group) were analyzed after propensity score matching (1:1). The total POPF rate was 21.9%. POPF was identified in 12.5% (8/64) of the patients who underwent resection with lockstitch reinforcement and 31.2% (20/64) of the patients without reinforcement (odds ratio 0.314, 95% confidence interval 0.130-0.760, P=0.010). No deaths occurred in either group. Neither the major complication rate nor the length of hospital stay after surgery differed between the groups., Conclusions: Compared with the use of stapler alone, staple line lockstitch reinforcement for remnant closure during distal pancreatectomy could reduce the POPF rate. Further multicenter randomized clinical trials are required to confirm these results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Tian, Luo, Sun, Lu, Huang and Guo.)

Various methods of evaluating a humectant's moisture retention have unique mechanisms. Hence, for designing advanced or efficient ingredients of cosmetic products, a clear understanding of differences among methods is required. The aim of this study was to analyze the moisture-retention capacity of glycerin, a common ingredient in cosmetic products. Specifically, this study applied gravimetric analysis, transepidermal water loss (TEWL) analysis, and differential scanning calorimetry (DSC) to examine the evaporation of glycerin solutions of different concentrations. The results revealed that the moisture-retention capacity of glycerin increased with the glycerin concentration from 0 to 60 wt%, and glycerin at concentration of 60-70 wt% did not exhibit weight change during the evaporation process. When the glycerin concentration exceeded 70 wt%, moisture sorption occurred in the glycerin solution. Furthermore, the results revealed a deviation between the evaporation rates measured using gravimetric analysis and those measured using TEWL analysis. However, normalizing the results of these analyses yielded the relative evaporation rates to water, which were consistent between these two analyses. DSC thermograms further confirmed the consistent results and identified two hydrated water microstructures (nonfreezable water and free water) in the glycerin solutions, which explained why the measured evaporation rate decreased with the glycerin concentration. These findings can be applied to prove the moisture-retention capacity of a humectant in cosmetic products by different measuring methods., (© 2022. The Author(s).)

Lung cancer is the second most common cancer in men and women in the United States; however, it remains the leading cause of cancer-related death in the United States and worldwide. The most common but nonspecific symptom of lung cancer is cough. Associated symptoms, including hemoptysis or shortness of breath, or systemic symptoms, including anorexia or weight loss, greatly increase the likelihood of having lung cancer. Referral to a multidisciplinary lung cancer team, imaging, and confirmation through sputum cytology, thoracentesis, fine-needle aspiration, or mediastinoscopy are recommended. If lung cancer is confirmed, treatment options vary based on staging, histology, immunotherapy biomarker testing, and patient health status. Treatments include surgical resection, immunotherapy, chemotherapy, and/or radiotherapy. Family physicians should focus on primary prevention of lung cancer by encouraging tobacco cessation and early recognition by screening at-risk individuals and following guidelines for pulmonary nodules. As of 2021, the U.S. Preventive Services Task Force recommends annual lung cancer screening using low-dose computed tomography starting at 50 years of age in patients with a 20 pack-year history.

Objectives: Fibroblast growth factor receptor 3 (FGFR3) was revealed to have divergent, even opposite roles in different neoplasms. In pancreatic ductal adenocarcinoma (PDAC), its impact on biological behavior and prognosis was not well elucidated., Methods: Fibroblast growth factor receptor 3 was downregulated by RNA interference to explore its impact on cell proliferative proclivity in PDAC cells. Furthermore, tissue microarray-based immunohistochemistry for FGFR3 was performed in 326 patients with PDAC who underwent radical resection, and its clinicopathologic and prognostic implications were then evaluated., Results: First, successful FGFR3 knockdown remarkably decreased its expression, cell proliferation, and S-phase ratio in the cell cycle in 2 PDAC cell lines, BxPC-3 and AsPC-1. Meanwhile, alterations in p-Akt, cyclin D1, cyclin B1, and p21 were also observed. Subsequently, high nuclear FGFR3 expression, but not cytoplasmic, was significantly common in tumor tissues and positively associated with N stage and dismal overall survival in the entire cohort. In addition, nuclear FGFR3 expression was also prognostic in 10 of 14 subsets. Univariate and multivariate Cox regression analyses identified nuclear expression of FGFR3 as an independent prognosticator in the entire cohort., Conclusions: Our data showed that FGFR3 nuclear translocation contributes to cell proliferative potential and predicts poor long-term prognosis in PDAC after surgical resection., Competing Interests: The authors declare no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

The protocol outlines the steps for growing silica nanowires on various substrates such as glass and stainless-steel foil. Silica nanowires are grown by thermal chemical vapor deposition via a vapor-liquid-solid mechanism, in which silicon wafers are used as silicon sources and platinum films as catalysts. This protocol can be used to grow silica nanowires on other substrates such as quartz filter, quartz sphere, alumina plate, and silicon wafer, provided the substrate materials can tolerate the temperature during process heating. For complete details on the use and execution of this profile, please refer to Lee et al. (2019), Tsai and Shieh (2019), and Tsai et al. (2021)., Competing Interests: The authors declare no competing interests., (© 2021 The Author(s).)

Vascular impairment is a crucial factor associated with chronic muscle pain, but relevant research from the microcirculatory aspect is lacking. Here, we investigated the differences in neck muscle microcirculation detected through laser-doppler flowmetry (LDF) and cervical biomechanics by a videofluoroscopic image in asymptomatic participants and patients with postural neck and shoulder pain. To understand the mechanism behind the effect of myofascial treatment, transverse friction massage (TFM) was applied and the immediate effects of muscular intervention on microcirculation were monitored. In total, 16 asymptomatic participants and 22 patients (mean age = 26.3 ± 2.4 and 25.4 ± 3.2 years, respectively) were recruited. Their neck muscle microcirculation and spinal image sequence were assessed. The differences in the baseline blood flow between the asymptomatic and patient groups were nonsignificant. However, the standard deviations in the measurements of the upper trapezius muscle in the patients were significantly larger ( p < 0.05). Regarding the TFM-induced responses of skin microcirculation, the blood flow ratio was significantly higher in the patients than in the asymptomatic participants ( p < 0.05). In conclusion, postintervention hyperemia determined through noninvasive LDF may be an indicator for the understanding of the mechanism underlying massage therapies and the design of interventions for postural pain.

The emission factor (EF), the weight of potentially toxic elements (PTEs) per unit energy or weight of sinter produced were evaluated for coal-fired boilers and sintering furnaces integrated in a steel plant. From three coal-fired boilers, 15 samples were taken while 22 samples were taken from four sintering furnaces. Investigations were performed on the EF of lead, cadmium, mercury, arsenic and chromium (VI). The coefficient of variance for the first 3 samples from each PTE was used to decide whether 2 more samples were necessary for the investigation. Three samples were sufficient for Cr (VI), however, 5 samples were required for Pb, Cd, Hg, and As, since the variances in concentrations of the first three samples exceeded 20%. The ranges for the ratio of the laboratory-based EF to the default EF applied by the Environment Protection Administration (EPA Taiwan) for Pb, Cd, Hg, and As for the coal-fired boiler were 0.08-0.013, 0.014-0.017, 0.019-0.033, 0.047-0.066 and for the sintering furnaces were 0.059-0.232, 0.05-0.151, 0.05-0.364, and 0.067-0.824. The ratio for Cr (VI)- was constant at 0.005 for all the coal fired boilers while it ranged from 0.057-0.709 for the sintering furnaces. Whilst source identification, enrichment factors, and spatial distributions for PTEs are often studied, laboratory-based investigations on the EFs for PTEs from industrial plants are rarely performed. This study filled the information gap and compared the obtained EFs with the EPA default values. To avoid overcharging industrial plants equipped with the best available technology for emission control, the EPA should apply field investigations and laboratory-based EFs instead of the default EPA EFs to calculate air pollution fees. Insights from this investigation can be applied to promote the adoption of appropriate air pollution control devices to cut down the emission of PTEs., Competing Interests: Declaration of competing interest The authors declare that they are no known conflicts of interest which could have influenced the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

In this work, the development and application of multicomponents obtained from recycled polyethylene terephthalate ( r -PET) waste and monotropic liquid crystals as anticorrosion coatings are reported. The r -PET raw material was alcoholyzed and reproduced as a thermoplastic polyester elastomer (TPEE) with different amounts (n%, n = 0, 1, 3, and 5) of 1,6-hexanediamine (HDA). Then, a fluorine-containing liquid crystal (4-cyano-3-fluorophenyl 4-ethylbenzoate (4CFE)) was incorporated into the TPEE mixture via solvent blending to modify and enhance the water resistance. The adhesion behavior of the coating on glass and iron substrates was evaluated by cross-cut tests and immersion tests in aqueous NaCl. In the corrosion resistance measurements, all of the coating samples fabricated with 10 ± 1 mm thickness were less active toward electrochemical corrosion ( P EF % > 99%) than the bare iron plate, indicating that our work provided better protection against corrosion of the iron plate.

Si δ-doped AlGaAs/InGaAs/AlGaAs quantum well (QW) structure is commonly adopted as one of the core elements in modern electric and optoelectronic devices. Here, the time dependent photoconductivity spectra along the active InGaAs QW channel in a dual and symmetric Si δ-doped AlGaAs/InGaAs/AlGaAs QW structure are systematically studied under various temperatures (T = 80-300 K) and various incident photon energies (E in = 1.10-1.88 eV) and intensities. In addition to positive photoconductivity, negative photoconductivity (NPC) was observed and attributed to two origins. For T = 180-240 K with E in = 1.51-1.61 eV, the trapping of the photo-excited electrons by the interface states located inside the conduction band of InGaAs QW layer is one of the origins for NPC curves. For T = 80-120 K with E in = 1.10-1.63 eV, the photoexcitation of the excess 'supersaturated' electrons within the active InGaAs QW caused by the short cooling process is another origin.

How the nervous system regulates bone remodeling is an exciting area of emerging research in bone biology. Accumulating evidence suggest that neurotransmitter-mediated inputs from neurons may act directly on osteoclasts. Dopamine is a neurotransmitter that can be released by hypothalamic neurons to regulate bone metabolism through the hypothalamic-pituitary-gonadal axis. Dopamine is also present in sympathetic nerves that penetrate skeletal structures throughout the body. It has been shown that dopamine suppresses osteoclast differentiation via a D2-like receptors (D2R)-dependent manner, but the intracellular secondary signaling pathway has not been elucidated. In this study, we found that cAMP-response element binding protein (CREB) activity responds to dopamine treatment during osteoclastogenesis. Considering the critical role of CREB in osteoclastogenesis, we hypothesize that CREB may be a critical target in dopamine's regulation of osteoclast differentiation. We confirmed that D2R is also present in RAW cells and activated by dopamine. Binding of dopamine to D2R inhibits the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway which ultimately decreases CREB phosphorylation during osteoclastogenesis. This was also associated with diminished expression of osteoclast markers that are downstream of CREB. Pharmacological activation of adenylate cyclase (to increase cAMP production) and PKA reverses the effect of dopamine on CREB activity and osteoclastogenesis. Therefore, we have identified D2R/cAMP/PKA/CREB as a candidate pathway that mediates dopamine's inhibition of osteoclast differentiation. These findings will contribute to our understanding of how the nervous and skeletal systems interact to regulate bone remodeling. This will enable future work toward elucidating the role of the nervous system in bone development, repair, aging, and degenerative disease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Competing Interests: The authors have no conflicts of interest relevant to this article.

Objective: To evaluate the clinical application of indocyanine green (ICG) visualization by near infrared fluorescence laparoscopy (NIFL) in complex upper urinary tract reconstructions surgery., Methods: This was a retrospective study of 7 patients who underwent complex surgeries of ureteral reconstruction between May 2019 and October 2019. There were 6 males and 1 female with the age ranging from 24 to 57 years (median age was 47 years). There were 5 cases of right ureteral strictures, of which 3 were proximal ureteral strictures and 2 were multiple and long ureteral strictures caused by radiotherapy. There were 2 cases of left ureteral strictures, of which 1 was ureteropelvic junction stricture and 1 was proximal ureteral stricture. There were 4 cases of secondary repair operations and 3 cases of primary operations. All the patients underwent laparoscopic surgery via the abdominal approach. ICG was injected into the ureter via nephrostomy tube during the operations, and the diseased ureter was identified by NIFL. Among the patients, 2 cases underwent IUPU (Institute of Urology, Peking University) modified ileal ureter replacement, 2 cases underwent ureteroureterostomy, 2 cases underwent appendiceal onlay flap ureteroplasty, and 1 case underwent lingual mucosa onlay flap ureteroplasty., Results: All the operations were successfully completed without open conversion. The localization and separation of ureteral lesions were completed under NIFL. The mean operative time was 187 (135-300) min. The duration of ureteral separation was 15-27 min, and the mean time was 18 min. The estimated blood loss was 15-200 mL, the mean estimated blood loss was 50 mL. There was one patient with ileal ureter replacement who had fever after surgery and responded well to antibiotics. The mean (range) length of postoperative hospital stay was 7 (6-10) days and no postoperative complications of a high grade (Clavien-Dindo Ⅲ and Ⅳ) occurred. Up to now, the mean follow-up duration was 9 (6-11) months, and no indocyanine green toxicity occurred. All D-J stents and nephrostomy were removed successfully 2 months after the operation. Ultrasound showed no obvious hydronephrosis, and CTU (computed tomography urography) showed that the urinary tract was unobstructed and the kidney function was normal., Conclusion: The application of ICG in the complex upper urinary tract reconstructive surgery is a safe and easy method to help surgeon to identify the ureter which may reduce the risk of iatrogenic damage and protect the ureteral blood supply.

Objective: Cigarette smoking promotes endothelial dysfunction and is a prominent catalyst for vascular disease. This study employed laser doppler flowmetry (LDF) and spectral analysis to investigate the skin microvascular response to relatively mild stimulus of stretching in diabetic smokers., Methods: The study population consisted of thirty type 2 diabetic male patients (15 smokers vs. 15 non-smokers) and 15 normal non-smoking subjects. The cutaneous blood flow of the calf at both lower limbs was measured by LDF at a supine position throughout and after muscle stretching by passive dorsiflexion of the ankle., Results: Following the stretch, post-stretch reactive hyperemia (PSRH) responses were found in all subjects. However, the diabetic non-smokers had relatively higher reactive blood flow than that of the diabetic smokers. The PSRH sustained for a longer time in both diabetic non-smokers and non-diabetic non-smokers in the time domain analysis. By spectral analysis, an observed discrepancy between that of diabetic smokers and diabetic non-smokers was statistically significant. Specifically, the frequency intervals corresponded to a nitric oxide dependent endothelial activity. In addition, an excessive response induced by stretching in frequency intervals of neurogenic activity, when compared with the non-smoking control, was found on diabetic non-smokers., Conclusion: All subjects expressed the PSRH effect in cutaneous microcirculation after a 10-s stretch stimulus; however, this effect was observed at a significantly lower intensity in chronic smokers with diabetes. The spectral analysis of the skin blood flow signals provides a pathological index for the assessment of the endothelial dysfunction induced by cigarette smoking. Furthermore, the discrepancy of neurovascular function between that of diabetic non-smokers and normal subjects could also be distinguished via the variations of the spectrum related to neurogenic activity., (Copyright © 2020 Low, Lin, Huang, Chia, Bau and Huang.)

Pancreatic neuroendocrine tumors (pNETs) are a heterogeneous group of tumors with complicated treatment options that depend on pathological grading, clinical staging, and presence of symptoms related to hormonal secretion. With regard to diagnosis, remarkable advances have been made: Chromogranin A is recommended as a general marker for pNETs. But other new biomarker modalities, like circulating tumor cells, multiple transcript analysis, microRNA profile, and cytokines, should be clarified in future investigations before clinical application. Therefore, the currently available serum biomarkers are insufficient for diagnosis, but reasonably acceptable in evaluating the prognosis of and response to treatments during follow-up of pNETs. Surgical resection is still the only curative therapeutic option for localized pNETs. However, a debulking operation has also been proven to be effective for controlling the disease. As for drug therapy, steroids and somatostatin analogues are the first-line therapy for those with positive expression of somatostatin receptor, while everolimus and sunitinib represent important progress for the treatment of patients with advanced pNETs. Great progress has been achieved in the combination of systematic therapy with local control treatments. The optimal timing of local control intervention, planning of sequential therapies, and implementation of multidisciplinary care remain pending., Competing Interests: Conflict-of-interest statement: The authors declare no conflict of interest., (©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.)

Genome-wide association studies (GWAS) have identified Optineurin (OPTN) as genetically linked to Paget's disease of the bone (PDB), a chronic debilitating bone remodeling disorder characterized by localized areas of increased bone resorption and abnormal bone remodeling. However, only ~10% of mouse models with a mutation in Optn develop PDB, thus hindering the mechanistic understanding of the OPTN-PDB axis. Here, we reveal that 100% of aged Optn global knockout (Optn -/- ) mice recapitulate the key clinical features observed in PDB patients, including polyostotic osteolytic lesions, mixed-phase lesions, and increased serum levels of alkaline phosphatase (ALP). Differentiation of primary osteoclasts ex vivo revealed that the absence of Optn resulted in an increased osteoclastogenesis. Mechanistically, Optn-deficient osteoclasts displayed a significantly decreased type I interferon (IFN) signature, resulting from both defective production of IFNβ and impaired signaling via the IFNα/βR, which acts as a negative feedback loop for osteoclastogenesis and survival. These data highlight the dual roles of OPTN in the type I IFN response to restrain osteoclast activation and bone resorption, offering a novel therapeutic target for PDB. Therefore, our study describes a novel and essential mouse model for PDB and define a key role for OPTN in osteoclast differentiation.

Osteoporosis deteriorates bone mass and biomechanical strength, becoming a life-threatening cause to the elderly. MicroRNA is known to regulate tissue remodeling; however, its role in the development of osteoporosis remains elusive. In this study, we uncovered that silencing miR-29a expression decreased mineralized matrix production in osteogenic cells, whereas osteoclast differentiation and pit formation were upregulated in bone marrow macrophages as co-incubated with the osteogenic cells in transwell plates. In vivo, decreased miR-29a expression occurred in ovariectomy-mediated osteoporotic skeletons. Mice overexpressing miR-29a in osteoblasts driven by osteocalcin promoter (miR-29aTg/OCN) displayed higher bone mineral density, trabecular volume and mineral acquisition than wild-type mice. The estrogen deficiency-induced loss of bone mass, trabecular morphometry, mechanical properties, mineral accretion and osteogenesis of bone marrow mesenchymal cells were compromised in miR-29aTg/OCN mice. miR-29a overexpression also attenuated the estrogen loss-mediated excessive osteoclast surface histopathology, osteoclast formation of bone marrow macrophages, receptor activator nuclear factor-κ ligand (RANKL) and C-X-C motif chemokine ligand 12 (CXCL12) expression. Treatment with miR-29a precursor improved the ovariectomy-mediated skeletal deterioration and biomechanical property loss. Mechanistically, miR-29a inhibited RANKL secretion in osteoblasts through binding to 3'-UTR of RANKL. It also suppressed the histone acetyltransferase PCAF-mediated acetylation of lysine 27 in histone 3 (H3K27ac) and decreased the H3K27ac enrichment in CXCL12 promoters. Taken together, miR-29a signaling in osteogenic cells protects bone tissue from osteoporosis through repressing osteoclast regulators RANKL and CXCL12 to reduce osteoclastogenic differentiation. Arrays of analyses shed new light on the miR-29a regulation of crosstalk between osteogenic and osteoclastogenic cells. We also highlight that increasing miR-29a function in osteoblasts is beneficial for bone anabolism to fend off estrogen deficiency-induced excessive osteoclastic resorption and osteoporosis.

The δ subunit-containing GABAA receptor [GABAA(δ)R], which is exclusively situated in the extrasynaptic space, has considerable influence on emotion and behavior. Although the expression of this receptor experiences dramatic fluctuation during postnatal development, it remains unknown whether it regulates emotion in a development-dependent manner. Here, by using mice with genetic deletion of GABAA(δ)R (knockout) and their wild-type littermates, we examined the role of GABAA(δ)R in regulating anxiety-like behavior, as measured with open field test (OFT) and elevated plus maze during the transition from puberty to adulthood. We observed that for female mice, the knockout ones at puberty but not adulthood showed increased anxiety-like behavior in the OFT relative to their wild-type littermates. However, such increase was not observed in elevated plus maze. For male mice, no between-genotype differences were observed in both tests at the above two developmental stages. Our results suggest that GABAA(δ)R preferentially affects the anxiety-like behavior in OFT in a development-dependent manner, but only in female mice.