Angiotensin-converting enzyme 2 alleviates liver fibrosis through the renin-angiotensin system.

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.

Occurrence and seasonal variation of Perkinsus sp. Infection in wild mollusk populations from coastal waters of Qingdao, northern China.

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.

The Probiotic Bacillus hwajinpoensis Colonizes the Digestive System of Crassostrea gigas Larvae and Protects Them from Vibrio alginolyticus Infection.

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 105 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.

Identification and Characterization of Infectious Pathogens Associated with Mass Mortalities of Pacific Oyster (Crassostrea gigas) Cultured in Northern China.

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.

High-mobility and low subthreshold swing amorphous InGaZnO thin-film transistors byin situH2plasma and neutral oxygen beam irradiation treatment.

In this work, staggered bottom-gate structure amorphous In-Ga-Zn-O (a-IGZO) thin film transistors (TFTs) with high-k ZrO2gate dielectric were fabricated using low-cost atmospheric pressure-plasma enhanced chemical vapor deposition (AP-PECVD) within situhydrogenation 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-1and high field-effect mobility of 35 cm2V-1s-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 H2plasma with NOBI-treated a-IGZO/ZrO2TFT is a promising candidate for transparent electronic device applications.

Surgical Treatment of Pineal Region Tumors: An 18 year-Experience at a Single Institution.

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.

Investigating adolescent mental health of Chinese students during the COVID-19 pandemic: Multicenter cross-sectional comparative investigation.

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.

Staple line lockstitch reinforcement decreases clinically relevant pancreatic fistula following distal pancreatectomy: Results of a propensity score matched retrospective analysis.

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.

FGFR3 Nuclear Translocation Contributes to Proliferative Potential and Poor Prognosis in Pancreatic Ductal Adenocarcinoma.

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.

Protocol for growing silica nanowires on various substrates to enhance superwetting and self-jumping properties.

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).

Myofascial Treatment for Microcirculation in Patients with Postural Neck and Shoulder Pain.

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.

Dopamine suppresses osteoclast differentiation via cAMP/PKA/CREB pathway.

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.

Impaired Microvascular Response to Muscle Stretching in Chronic Smokers With Type 2 Diabetes.

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.

Pancreatic neuroendocrine tumors: A review of serum biomarkers, staging, and management.

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.

Global deletion of Optineurin results in altered type I IFN signaling and abnormal bone remodeling in a model of Paget's disease.

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 IFNß and impaired signaling via the IFNα/ßR, 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.

Dramatic Improvement of the Mechanical Strength of Silane-Modified Hydroxyapatite-Gelatin Composites via Processing with Cosolvent.

Bone tissue engineering (BTE) requires a sturdy biomaterial for scaffolds for restoration of large bone defects. Ideally, the scaffold should have a mechanical strength comparable to the natural bone in the implanted site. We show that adding cosolvent during the processing of our previously developed composite of hydroxyapatite-gelatin with a silane cross-linker can significantly affect its mechanical strength. When processed with tetrahydrofuran (THF) as the cosolvent, the new hydroxyapatite-gelatin composite can demonstrate almost twice the compressive strength (97 vs 195 MPa) and biaxial flexural strength (222 vs 431 MPa) of the previously developed hydroxyapatite-gelatin composite (i.e., processed without THF), respectively. We further confirm that this mechanical strength improvement is due to the improved morphology of both the enTMOS network and the composite. Furthermore, the addition of cosolvents does not appear to negatively impact the cell viability. Finally, the porous scaffold can be easily fabricated, and its compressive strength is around 11 MPa under dry conditions. All these results indicate that this new hydroxyapatite-gelatin composite is a promising material for BTE application.

Using KrF ELA to Improve Gate-Stacked LaAlO3/ZrO2 Indium Gallium Zinc Oxide Thin-Film Transistors with Novel Atmospheric Pressure Plasma-Enhanced Chemical Vapor Deposition Technique.

Atmospheric pressure plasma-enhanced chemical vapor deposition (AP-PECVD) technique and KrF excimer laser annealing (ELA) were employed for the fabrication of indium gallium zinc oxide thin-film transistors (IGZO-TFTs). Device with a 150 mJ/cm2 laser annealing densities demonstrated excellent electrical characteristics with improved on/off current ratio of 4.7×107, high channel mobility of 10 cm2/V-s, and low subthreshold swing of 0.15 V/dec. The improvements are attributed to the adjustment of oxygen vacancies in the IGZO channel to an appropriate range of around 28.3% and the reduction of traps at the high-k/IGZO interface.

Investigation of Gate-Stacked In-Ga-Zn-O TFTs with Ga-Zn-O Source/Drain Electrodes by Atmospheric Pressure Plasma-Enhanced Chemical Vapor Deposition.

Atmospheric pressure plasma-enhanced chemical vapor deposition (AP-PECVD) was employed for the fabrication of indium gallium zinc oxide thin-film transistors (IGZO TFTs) with high transparent gallium zinc oxide (GZO) source/drain electrodes. The influence of post-deposition annealing (PDA) temperature on GZO source/drain and device performance was studied. Device with a 300 °C annealing demonstrated excellent electrical characteristics with on/off current ratio of 2.13 × 108, saturation mobility of 10 cm2/V-s, and low subthreshold swing of 0.2 V/dec. The gate stacked LaAlO3/ZrO2 of AP-IGZO TFTs with highly transparent and conductive AP-GZO source/drain electrode show excellent gate control ability at a low operating voltage.