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ObjectiveVitamin D/Vitamin D receptor (VD/VDR) signaling and the Notch pathway are involved in intestinal barrier restoration in colitis; however, their relationship and underlying mechanism are largely unknown. Therefore, this study aimed to investigate the role and mechanism of VD/VDR and the Notch pathways in intestinal barrier protection.MethodsGenetic Vdr knockout (VDR KO) and VD deficient (VDd) mice were established, and colitis was induced by feeding 2.5% dextran sodium sulfate (DSS) water. Mechanistic studies, including real-time PCR, immunofluorescence, Western blotting and dual-luciferase reporter assays, were performed on cultured Caco-2 cells and intestinal organoids.ResultsVD deficiency and VDR genetical KO increased the severity of DSS-induced colitis in mice, which presented a higher disease activity index score, increased intestinal permeability, and more severe intestinal histological damage than controls, accompanied by decreased and disrupted claudin-1 and claudin-3. Moreover, inhibition of Notch pathway by LY411,575 aggravated the severity of DSS-induced colitis and intestinal injury. In Caco-2 cells and intestinal organoids, the expression of Notch-1, N1ICD and Hes1 decreased upon downregulation or KO of VDR but increased upon paricalcitol (PAR, a VDR agonist) treatment. Meanwhile, PAR rescued claudin-1 and claudin-3 impairments that resulted from TNF-α exposure but failed to restore claudin-3 upon Notch inhibition. The dual-luciferase reporter assay further suggested that VD/VDR positively regulated the Notch signaling pathway by modulating Notch-1 transcription.ConclusionVD/VDR positively modulates Notch activation by promoting Notch-1 transcription to maintain intestinal tight junction integrity and barrier function. This highlights the VD/VDR-Notch pathway as a potential new therapeutic target for protecting the intestinal barrier against ulcerative colitis.

Summary: Background: To date, because of the difficulty in obtaining normal parathyroid gland samples in human or in animal models, our understanding of this last-discovered organ remains limited. Methods: In the present study, we performed a single-cell transcriptome analysis of six normal parathyroid and eight parathyroid adenoma samples using 10 × Genomics platform. Findings: We have provided a detailed expression atlas of parathyroid endocrine cells. Interestingly, we found an exceptional high expression levels of CD4 and CD226 in parathyroid endocrine cells, which were even higher than those in lymphocytes. This unusual expression of lymphocyte markers in parathyroid endocrine cells was associated with the depletion of CD4 T cells in normal parathyroid glands. Moreover, CD4 and CD226 expression in endocrine cells was significantly decreased in parathyroid adenomas, which was associated with a significant increase in Treg counts. Finally, along the developmental trajectory, we discovered the loss of POMC, ART5, and CES1 expression as the earliest signature of parathyroid hyperplasia. Interpretation: We propose that the loss of CD4 and CD226 expression in parathyroid endocrine cells, coupled with an elevated number of Treg cells, could be linked to the pathogenesis of parathyroid adenoma. Our data also offer valuable information for understanding the noncanonical function of CD4 molecule. Funding: This work was supported by the National Key R&D Program of China (2022YFA0806100), National Natural Science Foundation of China (82130025, 82270922, 31970636, 32211530422), Shandong Provincial Natural Science Foundation of China (ZR2020ZD14), Innovation Team of Jinan (2021GXRC048) and the Outstanding University Driven by Talents Program and Academic Promotion Program of Shandong First Medical University (2019LJ007).

Abstract Background Spontaneous bacterial peritonitis (SBP) is a life-threatening complication in patients with advanced cirrhosis. Prophylactic Norfloxacin used to be considered effective in SBP prevention, but in recent years its efficacy has been partially compromised by increasing quinolone-resistant bacteria. However, whether the effects of alternative prophylactic regimens are superior to norfloxacin remains controversial. The goal of this study is to compare the effects of norfloxacin with other antibiotics in SBP prophylaxis for cirrhotic patients. Methods We systematically searched Pubmed, Embase, and Cochrane Library Databases. Two reviewers independently identified relevant random control trials (RCTs) comparing the role of norfloxacin and other antibiotics in SBP prevention. Results Eight studies comprising 1043 cirrhotic patients were included in this study. Norfloxacin and alternative antibiotics displayed comparable effects in SBP prophylaxis, survival benefit, overall infection prevention, and safety. Subgroup analyses revealed that rifaximin prophylaxis could reduce the recurrence of SBP with fewer adverse events but failed to improve overall survival compared with norfloxacin. Conclusions Other antibiotics are a reasonable alternative to norfloxacin in the prophylaxis of SBP. Rifaximin prophylaxis could be an alternative choose of antibiotic for SBP prevention because of its better protective effect and safety.

For the new sandglass-type FPSO, the unique shape of its floating body with oblique side and external expansion can significantly improve the motion performance, but meanwhile may result in specific slamming characteristics in waves. On this basis, this paper establishes a CFD method including numerical wave-tank technique based on the Open FOAM platform. Therein, the velocity-inlet boundary method and the active absorption method are applied for numerical wave-making and wave-absorption. Compared with experimental results, the numerical method can be validated to be accurate enough to simulate wave slamming on floating ocean platforms. Then, the specific slamming phenomena on the sandglass-type floating body under a classic long wave can be investigated by comparing with the cylindrical model, including nonlinear wave rollover and breaking, water cushion, rooster-tail wave, side wave, water tongue, and so on. The mechanism of these phenomena and their effects on slamming pressure are studied. The essences of typical peaks in the time-history curve of the slamming pressure are mainly discussed. More interestingly, the main peak can be found to be related to the small peak due the amount of the broken water and the thickness of the water cushion. Finally, the slamming characteristics of the sandglass-type model in a classic short-wave condition are comparatively discussed.

Background: Cholestasis is a common pathological process in a variety of liver diseases that may lead to liver fibrosis, cirrhosis, and even liver failure. Cholestasis relief has been regarded as a principal target in the management of multiple chronic cholestasis liver diseases like primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) at present. However, complicated pathogenesis and limited acknowledgments fettered therapeutic development. Therefore, this study aimed to systematically analyze miRNA-mRNA regulatory networks in cholestatic liver injury in order to provide new treatment strategies.Methods: Gene Expression Omnibus (GEO) database (GSE159676) was used to screen differentially expressed hepatic miRNAs and mRNAs in the PSC vs. control comparison and the PBC vs. control comparison, respectively. MiRWalk 2.0 tool was used to predict miRNA-mRNA pairs. Subsequently, functional analysis and immune cell infiltration analysis were performed to explore the pivotal functions of the target genes. RT-PCR was used to verify the result.Results: In total, a miRNA-mRNA network including 6 miRNAs (miR-122, miR-30e, let-7c, miR-107, miR-503, and miR-192) and 8 hub genes (PTPRC, TYROBP, LCP2, RAC2, SYK, TLR2, CD53, and LAPTM5) was constructed in cholestasis. Functional analysis revealed that these genes were mainly involved in the regulation of the immune system. Further analysis revealed that resting memory CD4 T cells and monocytes could potentially participate in cholestatic liver injury. The expressions of DEMis and eight hub genes were verified in ANIT-induced and BDL-induced cholestatic mouse models. Furthermore, SYK was found to have an impact on the response to UDCA, and its mechanism was possibly associated with complement activation and monocyte reduction.Conclusion: In the present study, a miRNA-mRNA regulatory network was constructed in cholestatic liver injury, which mostly mediated immune-related pathways. Moreover, the targeted gene SYK and monocytes were found to be related to UDCA response in PBC.

Abstract Background The most common etiologies of Cushing's syndrome (CS) are adrenocorticotropic hormone (ACTH)‐producing pituitary adenoma (pitCS) and primary adrenal gland disease (adrCS), both of which burden patients with metabolic disturbance. The aim of this study was to compare the metabolic features of pitCS and adrCS patients. Methods A retrospective review including 114 patients (64 adrCS and 50 pitCS) diagnosed with CS in 2009–2019 was performed. Metabolic factors were then compared between pitCS and adrCS groups. Results Regarding sex, females suffered both adrCs (92.2%) and pitCS (88.0%) more frequently than males. Regarding age, patients with pitCS were diagnosed at a younger age (35.40 ± 11.94 vs. 39.65 ± 11.37 years, p = 0.056) than those with adrCS, although the difference was not statistically significant. Moreover, pitCS patients had much higher ACTH levels and more serious occurrences of hypercortisolemia at all time points (8 AM, 4 PM, 12 AM) than that in adrCS patients. Conversely, indexes, including body weight, BMI, blood pressure, serum total cholesterol, low density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C), triglycerides, fasting plasma glucose, and uric acid, showed no differences between adrCS and pitCS patients. Furthermore, diabetes prevalence was higher in pitCS patients than in adrCS patients; however, there were no significant differences in hypertension or dyslipidemia prevalence between the two. Conclusions Although adrCS and pitCS had different pathogenetic mechanisms, different severities of hypercortisolemia, and different diabetes prevalences, both etiologies had similar metabolic characteristics.

Objectives: Vitamin D (VitD) and Vitamin D receptor (VDR) are suggested to play protective roles in the intestinal barrier in ulcerative colitis (UC). However, the underlying mechanisms remain elusive. Evidence demonstrates that Na+/H+ exchanger isoform 8 (NHE8, SLC9A8) is essential in maintaining intestinal homeostasis, regarded as a promising target for UC therapy. Thus, this study aims to investigate the effects of VitD/VDR on NHE8 in intestinal protection. Methods: VitD-deficient mice, VDR−/− mice and NHE8−/− mice were employed in this study. Colitis mice were established by supplementing DSS-containing water. Caco-2 cells and 3D-enteroids were used for in vitro studies. VDR siRNA (siVDR), VDR over-expression plasmid (pVDR), TNF-α and NF-κb p65 inhibitor QNZ were used for mechanical studies. The expression of interested proteins was detected by multiple techniques. Results: In colitis mice, paricalcitol upregulated NHE8 expression was accompanied by restoring colonic mucosal injury. In VitD-deficient and VDR−/− colitis mice, NHE8 expression was compromised with more serious mucosal damage. Noteworthily, paricalcitol could not prevent intestinal barrier dysfunction and histological destruction in NHE8−/− mice. In Caco-2 cells and enteroids, siVDR downregulated NHE8 expression, further promoted TNF-α-induced NHE8 downregulation and stimulated TNF-α-induced NF-κb p65 phosphorylation. Conversely, QNZ blocked TNF-α-induced NHE8 downregulation in the absence or presence of siVDR. Conclusions: Our study indicates depressed NHE8 expression is responsible for VitD-deficient-induced colitis aggravation. These findings provide novel insights into the molecular mechanisms of VitD/VDR in intestine protection in UC.

With the increase in potential uses of terahertz technology, the need for terahertz transceivers with application-oriented adaptive radiation patterns has emerged. Reconfigurable reflectarrays consisting of actuated sub-wavelength reflectors have been successfully used for terahertz beam steering and beamforming. They do not require a complex feeding network and associated electronics, enabling a compact and power-efficient terahertz beam steering system. However, the current reflectarray-based beam steering is accomplished by forming the reflectarray as a grating structure, which is accompanied by the problems such as grating lobes, limited steering range, and discrete steering angles. Here, we configure a MEMS-based reflectarray with the genetic algorithm to eliminate the grating lobes and open up the possibility of customizing its radiation pattern. We used single- and multi-objective optimization to find the optimal height profile of the reflectarray and verified the results by full-wave electromagnetic simulations. We measured the radiation patterns of four reflectarray phantoms, i.e. reflectarrays without the MEMS actuation systems. The measurement results agree well with the calculated ones, with the main beam deviating at most 2° from the target direction. Our work demonstrates how a genetic algorithm is used to shape a reconfigurable terahertz reflectarray to eliminate the grating lobes and tailor some specific featuress in its radiation pattern.

IntroductionThe parathyroid glands are important endocrine glands for maintaining calcium and phosphorus metabolism, and they are vulnerable to accidental injuries during thyroid cancer surgery. The aim of this retrospective study was to investigate the application of high-frequency ultrasound imaging for preoperative anatomical localization of the parathyroid glands in patients with thyroid cancer and to analyze the protective effect of this technique on the parathyroid glands and its effect on reducing postoperative complications.Materials and methodsA total of 165 patients who were operated for thyroid cancer in our hospital were included. The patients were assigned into two groups according to the time period of surgery: Control group, May 2018 to February 2021 (before the application of ultrasound localization of parathyroid in our hospital); PUS group, March 2021 to May 2022. In PUS group, preoperative ultrasound was used to determine the size and location of bilateral inferior parathyroid glands to help surgeons identify and protect the parathyroid glands during operation. We compared the preoperative ultrasound results with the intraoperative observations. Preoperative and first day postoperative serum calcium and PTH were measured in both groups.ResultsOur preoperative parathyroid ultrasound identification technique has more than 90% accuracy (true positive rate) to confirm the location of parathyroid gland compared to intraoperative observations. Postoperative biochemical results showed a better Ca2+ [2.12(0.17) vs. 2.05(0.31), P=0.03] and PTH [27.48(14.88) vs. 23.27(16.58), P=0.005] levels at first day post-operation in PUS group compared to control group. We also found a reduced risk of at least one type of hypoparathyroidism after surgery in control group:26 cases (31.0%) vs. 41 cases (50.6%), p=0.016.ConclusionUltrasound localization of the parathyroid glands can help in the localization, identification and in situ preservation of the parathyroid glands during thyroidectomy. It can effectively reduce the risk of hypoparathyroidism after thyroid surgery.

ObjectiveTo investigate the preventive effects of plant oils with different linoleic acid/alpha-linolenic acid (LA/ALA) ratios against colitis symptoms, and dysbiosis of gut microbiota in acute colitis mouse model.MethodsSixty male C57BL/6 mice were assigned into six groups (n = 10): three groups were fed low-fat diets with low, medium, and high LA/ALA ratios; and three groups were fed with high-fat diets with low, medium, and high LA/ALA ratios. After 3 months of diet, the mice were exposed to dextran sodium sulfate solution to induce acute colitis. The severity of colitis was estimated by disease activity index (DAI) and histopathological examination. 16S rRNA gene sequencing was used for the analysis of gut microbiota.ResultsPlant oils with a lower LA/ALA ratio showed higher alleviating effects on the symptoms of colitis, which were accompanied by the better prebiotic characteristics manifested as effectively inhibiting the abnormal expansion of phylum Proteobacteria and genus Escherichia-Shigella in the gut microbiota of colitis mouse models.ConclusionA potential IBD prevention strategy of reducing the LA/ALA ratio in the daily consumed plant oils was proposed in this study. Furthermore, based on the optimized LA/ALA ratio, this preventive effect might not be weakened by the high intake of plant oils.

Abstract Background Esophageal squamous cell carcinoma (ESCC) is one of the most malignant tumors in gastrointestinal system. MicroRNAs (miRNAs) have been reported to be implicated in cancer development. However, the role of miR-137 has not been fully revealed in ESCC. Methods Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analyses were separately used to examine RNA level and protein level. 5-ethynyl-2′-deoxyuridine (EdU) assay, transwell assays and flow cytometry analyses were conducted to assess biological behaviors of ESCC cells. Additionally, the interaction between genes were analyzed via Chromatin Immunoprecipitation (ChIP) assay, RNA Binding Protein Immunoprecipitation (RIP) assay, RNA pull down assay and luciferase reporter assay. Results MiR-137 was down-regulated in ESCC cells. Upregulation of miR-137 hindered ESCC cell proliferation, migration, invasion and epithelial mesenchymal transition (EMT). Besides, miR-137 enhanced the sensitivity of ESCC cells to irradiation. Moreover, CCCTC-binding factor (CTCF) inactivated miR-137 transcription in ESCC cells. Furthermore, we revealed enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) and paxillin (PXN) as the downstream targets of miR-137. In turn, EZH2 was recruited by CTCF and induced methylation in miR-137 promoter. Conclusion CTCF/Suz12/EZH2 complex-silenced miR-137 facilitates ESCC progression and radioresistance by targeting EZH2 and PXN.

Abstract Quantum dots (QDs) as emerging light-converting materials show the advantage of enhancing color quality of white light-emitting diode (WLED). However, WLEDs employing narrow-emitting monochromic QDs usually present unsatisfactory color rendering in the orange region. Herein, composite orange-red QDs (composite-QDs) are developed through mixing CdSe/ZnS-based orange QDs (O-QDs) and red QDs (R-QDs) to compensate the orange-red light for WLEDs. We investigated the effect of self-absorption and fluorescence resonance energy transfer (FRET) process in composite-QDs on the spectral controllability and fluorescent quenching in WLEDs. The concentration and donor/acceptor ratios were also taken into account to analyze the FRET efficiency and help identify suitable composite-QDs for color compensation in the orange-red light region. As the result, the optimized composite-QDs effectively improve the color rendering index of the WLED compared with monochromatic QDs.

Abstract Perovskite quantum dots (QDs) have been widely used in white light-emitting diodes (WLEDs), due to their high quantum yield (QY), tunable bandgap, and simple preparation. However, the red-emitting perovskite QDs are usually containing iodine (I), which is not stable under continuous light irradiation. Herein, perovskite-based WLED is fabricated by lead-free bismuth (Bi)-doped inorganic perovskites Cs2SnCl6 and less-lead Mn-doped CsPbCl3 QDs, which emits white light with color coordinates of (0.334, 0.297). The Bi-doped Cs2SnCl6 and Mn-doped CsPbCl3 QDs both show excellent stability when kept in the ambient air. As benefits from this desired characteristic, the as-prepared WLED shows excellent stability along with operating time. These results can promote the application of inorganic perovskite QDs in the field of WLEDs.

In this work, we investigate the effect of sidewall angle, height and space of an air cavity extractor (AC-Extractor) on the polarization-dependent light extraction efficiency (LEE) for AlGaN-based deep-ultraviolet light-emitting diodes (DUV LEDs) using three-dimensional finite difference time-domain method. Compared to the reported inclined sidewall metal reflector (SM-Reflector), DUV LED with AC-Extractor shows better light extraction at any height and inclined angle due to different light extraction mechanisms. The light in SM-Reflector DUV LED is extracted mainly through mirror reflection. However, total internal reflection from the sidewall dominants the contribution to LEE for the AC-Extractor with smaller inclined angle such that the space has little impact, while Fresnel scattering is more important for the AC-Extractor with larger inclined angle and that the additional out-light channel as well as the space play a critical role in enhancing the LEE. And the analysis is further developed into a three-escape-cones analytic model theory. In particular, the AC-Extractor with vertical sidewall is more beneficial to enhance the LEE of DUV LED than that with inclined sidewall, which can be rationally explained based on the three-escape-cones analytic model.

Large-scale two-dimensional air-gap photonic crystals (PhCs) were embedded in an n-type GaN layer to enhance the light emission of GaN-based light-emitting diodes (LEDs). The embedded-PhCs were obtained through overgrowth on n-GaN templates, which had air holes array previously fabricated by using nanosphere lithography technology. The effects of the distance D from active region to PhCs on the light extraction efficiency (LEE) of LEDs are investigated by experiments and finite difference-time domain simulation. The PhC LEDs with D = 2370 nm showed an improved light output power by 80.8% on average at forward current of 350 mA without degradation of electrical performance compared to conventional LEDs. It is mainly attributed to the improved LEE by enhancing the interaction of the guided modes and the embedded air-gap PhCs.

In this paper, we investigate the electron injection efficiency in terms of different polarities and different polarization charge densities at the GaN/InGaN interface. We find that the growth orientation for the GaN/InGaN-type last quantum barrier is essentially vital, i.e., the GaN/InGaN-type last quantum barrier is not able to effectively reduce the electron leakage and will degrade the light-emitting diode (LED) performance when the GaN/InGaN interface is [000-1] polarized. However, a suppressed electron leakage and enhanced optical power can be obtained for III-nitride LEDs grown along the [0001] orientation when the GaN/InGaN interface possesses polarization-induced negative charges. We conclude that the polarization-induced negative charges at the [0001] oriented GaN/InGaN interface facilitate the surface depletion in the GaN region, i.e., the conduction band of the GaN region is bent in the way of favoring electron depletion and contributes to an enhanced conduction band barrier height for electrons.

CdSe/CdS core-shell quantum rods (QRs) are a promising prospect in optoelectronic applications but usually have a relatively low quantum efficiency and stability. Here, we report on an efficient and stable CdSe/CdS/ZnS QRs-in-matrix assembly (QRAs) by growing and embedding CdSe/CdS QRs in ZnS matrices. Structural characterizations show that the CdSe/CdS QRs are encapsulated and interconnected by ZnS in the QRAs structure. The stable ZnS encapsulation renders the CdSe/CdS QRs high quantum efficiency (QE) up to 85%. The QRAs also present high photo- and thermal-stability and can preserve 93% of the initial QE at 100 °C. The QRAs powder presents a light degradation of only 2% under continuous excitation for 100 h, displaying profound potential in optoelectronic applications. White light-emitting diodes (WLEDs) are fabricated by packaging the QRAs powder as phosphor on top of blue GaN chip. The WLED shows high optical performance and light quality.

With the increased use of neoadjuvant chemotherapy (NAC) in breast cancer, the timing of sentinel lymph node biopsy (SLNB) has become increasingly important. In this study, we aimed to evaluate the feasibility and accuracy of SLNB for initially clinically node-negative breast cancer after NAC by conducting a systematic review and meta-analysis.We searched PubMed, Embase, and the Cochrane Library from January 1, 1993 to November 30, 2015 for studies on initially clinically node-negative breast cancer patients who underwent SLNB after NAC followed by axillary lymph node dissection (ALND).A total of 1,456 patients from 16 studies were included in this review. The pooled identification rate (IR) for SLNB was 96% [95% confidence interval (CI): 95%-97%], and the false negative rate (FNR) was 6% (95% CI: 3%-8%). The pooled sensitivity, negative predictive value (NPV) and accuracy rate (AR) were 94% (95% CI: 92%-97%, I2 = 27.5%), 98% (95% CI: 98%-99%, I2 = 42.7%) and 99% (95% CI: 99%-100%, I2 = 32.6%), respectively. In the subgroup analysis, no significant differences were found in either the IR of an SLNB when different mapping methods were used (P = 0.180) or in the FNR between studies with and without immunohistochemistry (IHC) staining (P = 0.241).Based on current evidence, SLNB is technically feasible and accurate enough for axillary staging in initially clinically node-negative breast cancer patients after NAC.

In this report, to tackle the thermal fluorescent quenching issue of II-VI semiconductor quantum dots (QDs), which hinders their on-chip packaging application to light-emitting diodes (LEDs), a QD-ZnS nanosheet inorganic assembly monolith (QD-ZnS NIAM) is developed through chemisorption of QDs on the surface of two-dimensional (2D) ZnS nanosheets and subsequent assembly of the nanosheets into a compact inorganic monolith. The QD-ZnS NIAM could reduce the thermal fluorescent quenching of QDs effectively, possibly due to fewer thermally induced permanent trap states and decreased Förster resonance energy transfer (FRET) among QDs when compared with those in a reference QD composite thin film. We have demonstrated that the QD-ZnS NIAM enables QDs to be directly packaged on-chip in LEDs with over 90% of their initial luminance being retained at above 85 °C, showing advantage in LED application in comparison with conventional QD composite film.