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Abstract Background Solitary Punctate Chorioretinitis (SPC) is a recently identified form of punctate inner choroidopathy (PIC) characterized by a single lesion in the fovea of the macula. Previous studies with a maximum follow-up of 48 months were insufficient. Our review uncovered a case sustained for 91 months. Case presentation A 28-year-old young woman experienced with sudden visual loss in her right eye. Comprehensive examinations, including assessment of best-corrected visual acuity (BCVA), slit-lamp biomicroscopy, noncontact tonometry, fundus fluorescein angiography (FFA), fundus autofluorescence (FAF), optical coherence tomography angiography (OCTA), perimetry, and microperimetry, were conducted. Over 91 months, the lesion slightly enlarged, remained yellow-white and punctate, and stayed in the central macula of the posterior pole. OCT images depicted subsidence in the inner nuclear layer (INL), the outer plexiform layer (OPL), photoreceptor layer, and disruption of the external limiting membrane (ELM), ellipsoid zone, and retinal pigment epithelium (RPE)/Bruch’s membrane complex. Retinal herniation, focal choroidal excavation (FCE), and abnormal vessels in the choriocapillaris were noted. At the slab of the choriocapillaris, OCTA demonstrated that the lesion resembled a linear vascular structure, distinct from the structure of normal choriocapillaris. This confirmed the lesion as an abnormal vascular formation. FAF revealed a punctate hypo-autofluorescence lesion and abnormal hyper-autofluorescence near the optic disc and macula. FFA demonstrated a punctate hyper-fluorescent lesion inferotemporal to the fovea. The vascular structure remained stable without fluid exudation on OCT images, hence anti-vascular endothelial growth factor (anti-VEGF) treatment was not administered. Visual acuity improved from counting fingers to 0.07 in 52 days, reached 0.6 after 15 months, remained at 0.6 from 56 to 80 months, and returned to 0.8 after 91 months, although accompanied by local scotomas. The lesion pattern slightly enlarged without scarring. Conclusions Throughout long-term follow-up, we had long suspected the presence of choroidal neovascularization (CNV) and found the FCE in the last visit. Eventually, we concluded that SPC could potentially constitute a distinct subtype of PIC. The patient received no treatment, and vision recovered to 0.8. If CNV is suspected in SPC, anti-VEGF treatment may not be necessary without activity on OCT, but close monitoring is essential.

Abstract Background Uveal melanoma (UM) is the most common primary intraocular tumor in adults, and early detection is critical to improve the clinical outcome of this disease. In this study, the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 (an investigational medicinal product) positron emission tomography (PET) imaging in UM xenografts and UM patients were evaluated. The cell uptake, cell binding ability and in vitro stability of [18F]AlF-NOTA-PRGD2 were evaluated in 92-1 UM cell line. MicroPET imaging and biodistribution study of [18F]AlF-NOTA-PRGD2 were conducted in 92-1 UM xenografts. Then, UM patients were further recruited for evaluating the diagnostic effectiveness of [18F]AlF-NOTA-PRGD2 PET imaging (approval no. NCT02441972 in clinicaltrials.gov). In addition, comparison of [18F]AlF-NOTA-PRGD2 and 18F-labelled fluorodeoxyglucose ([18F]FDG) PET imaging in UM xenografts and UM patients were conducted. Results The in vitro data showed that [18F]AlF-NOTA-PRGD2 had a high cell uptake, cell binding ability and in vitro stability in 92-1 UM cell line. The in vivo data indicated that 92-1 UM tumors were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer in the subcutaneous and ocular primary UM xenografts model at 60 min post-injection. And the tumor uptake of the tracer was 2.55 ± 0.44%ID/g and 1.73 ± 0.15%ID/g at these two tissue locations respectively, at 7 days after animal model construction. The clinical data showed that tumors in UM patients were clearly visualized with the [18F]AlF-NOTA-PRGD2 tracer at 60 min post-injection. In addition, [18F]AlF-NOTA-PRGD2 tracer showed higher sensitivity and specificity for PET imaging in UM xenografts and UM patients compared to [18F]FDG tracer. Conclusion [18F]AlF-NOTA-PRGD2 PET imaging may be a more preferred approach in the diagnosis of primary UM compared to [18F]FDG PET imaging. Additionally, due to the high tumor-to-background ratio, [18F]AlF-NOTA-PRGD2 PET imaging seems also to be applicable for the diagnosis of UM patients with liver metastasis. Trial registration: ClinicalTrials.gov: NCT02441972, Registered 1 January 2012, https://clinicaltrials.gov/study/NCT02441972 .

Abstract The tunable properties of halide perovskite/two dimensional (2D) semiconductor mixed-dimensional van der Waals heterostructures offer high flexibility for innovating optoelectronic and photonic devices. However, the general and robust growth of high-quality monocrystalline halide perovskite/2D semiconductor heterostructures with attractive optical properties has remained challenging. Here, we demonstrate a universal van der Waals heteroepitaxy strategy to synthesize a library of facet-specific single-crystalline halide perovskite/2D semiconductor (multi)heterostructures. The obtained heterostructures can be broadly tailored by selecting the coupling layer of interest, and can include perovskites varying from all-inorganic to organic-inorganic hybrid counterparts, individual transition metal dichalcogenides or 2D heterojunctions. The CsPbI2Br/WSe2 heterostructures demonstrate ultrahigh optical gain coefficient, reduced gain threshold and prolonged gain lifetime, which are attributed to the reduced energetic disorder. Accordingly, the self-organized halide perovskite/2D semiconductor heterostructure lasers show highly reproducible single-mode lasing with largely reduced lasing threshold and improved stability. Our findings provide a high-quality and versatile material platform for probing unique optoelectronic and photonic physics and developing further electrically driven on-chip lasers, nanophotonic devices and electronic-photonic integrated systems.

Stem cell transplantation has emerged as a promising avenue in regenerative medicine, potentially facilitating tissue repair in degenerative diseases and injuries. This review comprehensively examines recent developments and challenges in stem cell transplantation. It explores the identification and isolation of various stem cell types, including embryonic, induced pluripotent, and adult stem cells derived from multiple sources. Additionally, the review highlights the tissue-specific applications of these stem cells, focusing on bone and cartilage regeneration, treatment of neurological disorders, and management of hematological conditions. Future advancements and effective resolution of current challenges will be crucial in fully realizing the potential of stem cell transplantation in regenerative medicine. With responsible and ethical practices, the field can potentially transform disease and injury treatment, ultimately improving the quality of life for countless individuals.

The cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) signaling pathway is one of the fundamental mechanisms of the body’s defense, which responds to the abnormal presence of double-stranded DNA in the cytoplasm to establish an effective natural immune response. In addition to detecting microbial infections, the cGAS pathway may be triggered by any cytoplasmic DNA, which is absent from the normal cytoplasm, and only conditions such as senescence and mitochondrial stress can lead to its leakage and cause sterile inflammation. A growing body of research has shown that the cGAS-STING pathway is strongly associated with sterile inflammation. In this study, we reviewed the regulatory mechanisms and biological functions of the cGAS-STING pathway through its involvement in aseptic inflammation in liver disease, kidney disease, and cellular senescence.

Fe-based amorphous coating was produced using high-velocity arc-spraying (HVAS), and then laser remelting (LR) technology was used to treat the as-sprayed coatings (ASC) to prepare the laser remelted coatings (LRC). The morphology, phase composition, microhardness, porosity, and corrosion property of the Fe-based amorphous coatings before and after LR were investigated. The outcomes demonstrated that the internal defects of the ASC were eliminated and the porosity was significantly reduced after LR, which was significant in dramatically enhancing corrosion resistance. After the LR procedure, the ASC's free corrosion potential (Ecorr) in 3.5 wt% NaCl solution increased, and the corrosion current density (Icorr) almost reduced by a factor of ten. Therefore, LR helped to strengthen the corrosion characteristics of Fe-based amorphous coating and improve its microstructure.

Abstract Phosphate is an important fertilizer in agriculture and electrochemical sensors based on cobalt (Co) are promising for measurement of phosphate. The deposition of Co onto conductive substrates to form a nano/microstructured Co layer with rich active sites is a typical strategy to improve detection performances. However, the widely used substrates show smooth surfaces, which cannot provide extra active sites. Herein, a high‐performance phosphate sensor is fabricated by generating Co nanoparticles (NPs) on a hierarchically porous laser‐induced graphene (LIG) matrix with a large surface area. Specifically, a Co layer is first electroplated on the LIG matrix. Nevertheless, the pores of LIG will be blocked by the dense Co layer so the performances of the fabricated LIG‐Co sensor exhibit limited enhancements. Therefore, a “nearly all etching (NAE)” technique is developed to transform the dense Co layer to dispersive Co NPs and re‐expose the pores of LIG, both increasing the active sites. Compared to the LIG‐Co sensor, the LIG‐Co NP sensor displays overall superiority. The response time, sensitivity, and linearity are enhanced from ≈60 to ≈10 s, from 0.012 to 0.069 V dec−1, and from 0.973 to 0.998, respectively. The LIG‐Co NP sensor also shows a decent anti‐interference capability.

AimDespite the significant therapeutic outcomes achieved in systemic treatments for liver hepatocellular carcinoma (LIHC), it is an objective reality that only a low proportion of patients exhibit an improved objective response rate (ORR) to current immunotherapies. Antibody-dependent cellular phagocytosis (ADCP) immunotherapy is considered the new engine for precision immunotherapy. Based on this, we aim to develop an ADCP-based LIHC risk stratification system and screen for relevant targets.MethodUtilizing a combination of single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data, we screened for ADCP modulating factors in LIHC and identified differentially expressed genes along with their involved functional pathways. A risk scoring model was established by identifying ADCP-related genes with prognostic value through LASSO Cox regression analysis. The risk scoring model was then subjected to evaluations of immune infiltration and immunotherapy relevance, with pan-cancer analysis and in vitro experimental studies conducted on key targets.ResultsBuilding on the research by Kamber RA et al., we identified GYPA, CLDN18, and IRX5 as potential key target genes regulating ADCP in LIHC. These genes demonstrated significant correlations with immune infiltration cells, such as M1-type macrophages, and the effectiveness of immunotherapy in LIHC, as well as a close association with clinical pathological staging and patient prognosis. Pan-cancer analysis revealed that CLDN18 was prognostically and immunologically relevant across multiple types of cancer. Validation through tissue and cell samples confirmed that GYPA and CLDN18 were upregulated in liver cancer tissues and cells. Furthermore, in vitro knockdown of CLDN18 inhibited the malignancy capabilities of liver cancer cells.ConclusionWe have identified an ADCP signature in LIHC comprising three genes. Analysis based on a risk scoring model derived from these three genes, coupled with subsequent experimental validation, confirmed the pivotal role of M1-type macrophages in ADCP within LIHC, establishing CLDN18 as a critical ADCP regulatory target in LIHC.

Two-dimensional (2D) nonlinear optical mediums with high and tunable light modulation capability can significantly stimulate the development of ultrathin, compact, and integrated optoelectronics devices and photonic elements. 2D carbides and nitrides of transition metals (MXenes) are a new class of 2D materials with excellent intrinsic and strong light-matter interaction characteristics. However, the current understanding of their photo-physical properties and strategies for improving optical performance is insufficient. To address this issue, we rationally designed and in situ synthesized a 2D Nb2C/MoS2 heterostructure that outperforms pristine Nb2C in both linear and nonlinear optical performance. Excellent agreement between experimental and theoretical results demonstrated that the Nb2C/MoS2 inherited the preponderance of Nb2C and MoS2 in absorption at different wavelengths, resulting in the broadband enhanced optical absorption characteristics. In addition to linear optical modulation, we also achieved stronger near infrared nonlinear optical modulation, with a nonlinear absorption coefficient of Nb2C/MoS2 being more than two times that of the pristine Nb2C. These results were supported by the band alinement model which was determined by the X-ray photoelectron spectroscopy (XPS) experiment and first-principal theory calculation. The presented facile synthesis approach and robust light modulation strategy pave the way for broadband optoelectronic devices and optical modulators.

Objective Laparoscopic transabdominal preperitoneal (TAPP) inguinal hernia repair poses certain challenges to less experienced surgeons. This study was performed to compare the clinical outcomes of modified tumescent laparoscopic TAPP (MT-TAPP) inguinal hernia repair versus conventional laparoscopic TAPP (CL-TAPP) inguinal hernia repair. Methods We retrospectively analyzed the perioperative data of patients with inguinal hernias who underwent either MT-TAPP repair (n = 57) or CL-TAPP repair (n = 54) at the General Surgery Department of Nanjing Yimin Hospital from November 2019 to June 2023. Results The durations of the total operation and the preperitoneal space dissection were shorter in the MT-TAPP than CL-TAPP group. The estimated blood loss volume was lower in the MT-TAPP than CL-TAPP group. The visual analogue scale scores recorded at the 12- and 24-hour postoperative time points showed significantly greater reductions in the MT-TAPP than CL-TAPP group. Conclusions Using liquid injection and gauze dissection is both safe and practical. This technique results in a shortened total operation time, less time spent on preperitoneal space dissection, decreased estimated blood loss, and less severe postoperative pain.

Objective Intramedullary spinal cavernous malformations (ISCMs) are rare vascular lesions of the spinal cord with unclear natural history and controversy over treatment. This study aimed to report a series of symptomatic ISCMs underwent microsurgical management to illustrate the natural history, clinical presentation, and surgical outcomes and to evaluate factors associated with hemorrhage events and neurological prognosis. Methods This single-center retrospective study included 29 consecutive patients with whose demographic, symptomology, imaging, neurological, and surgical data were collected. The risk for hemorrhage events and factors affecting surgical outcomes were retrospectively analyzed. Results There were 12 female (41.4%) and 17 male patients (58.6%), with an average age of 45.2 years (range, 17–69 years). The mean size of the lesion was 9.7 mm (range, 3–20 mm). Most patients had a bowel or/and bladder dysfunction symptom (n = 11, 37.9%), followed by sensory deficits (n = 5, 17.2%), gait disturbance (n = 5, 17.2%), pain (n = 4, 13.8%), and weakness (n = 4, 13.8%), most (n = 15, 51.7%) with a chronic onset. All patients received total resection without rehemorrhages after surgical resection in follow-up. Sixty-five point five percent patients (n = 19) improved, 13.8% (n = 4) remained stable, 20.7% (n = 6) got worsen. The overall annual hemorrhage risk was 2.1% per patient-year. A total of 27 hemorrhages occurred in the 18 patients, of which rehemorrhage rate increased to 50.0% (n = 9) with a previous history of hemorrhage. Patients with smaller lesion sizes were more likely to have hemorrhage or rehemorrhage events (p = 0.008). Recurrent hemorrhage of the lesions was a risk factor for neurological outcomes (p = 0.016). Conclusion The risk of rehemorrhage was significantly increased in symptomatic ISCM patients with a previous history of hemorrhage. Rehemorrhage was a risk factor for neurological outcomes. Patients can benefit from microsurgical treatment to avoid rehemorrhage and further neurological deterioration.

Abstract Background Oxaliplatin-induced peripheral neurotoxicity (OIPN) limits the dose of chemotherapy and seriously affects the quality of life. Huangqi Guizhi Wuwu Decoction (HGWD) is a classical Traditional Chinese Medicine (TCM) formula for the prevention of OIPN. However, its specific pharmacological mechanism of action remains unknown. Our study found that HGWD can effectively alleviate chronic OIPN and regulate intestinal flora. Therefore, we explored the mechanism of action of HGWD in alleviating chronic OIPN from the perspective of intestinal flora. Methods In this study, we established an OIPN model in C57BL/6 mice treated with different concentrations of HGWD. Mechanical pain and cold pain were assessed at certain time points, and samples of mice colon, dorsal root ganglion (DRG), serum, and feces were collected. Associated inflammation levels in the colon and DRG were detected using immunohistochemical techniques; the serum lipopolysaccharide (LPS) levels and associated inflammation were assessed using the appropriate kits; and 16S rRNA sequencing was used to examine the dynamic changes in gut microorganisms. Finally, established fecal microbiota transplantation (FMT) and antibiotic (ABX) pretreatment models were used to validate flora’s role in HGWD for chronic OIPN by pain scoring and related pathological analysis. Results HGWD treatment significantly alleviated pain sensitivity in chronic OIPN mice. Pathological results showed that HGWD treatment improved intestinal ZO-1 expression and reduced serum LPS levels and associated inflammatory factors in the colon, serum, and DRG. The 16S rRNA results showed that HGWD restored the composition of the intestinal flora in a time-dependent manner to alleviate OIPN. FMT and ABX experiments demonstrated that HGWD can alleviate chronic OIPN by regulating intestinal flora homeostasis. Conclusions HGWD prevents chronic OIPN by dynamically regulating intestinal flora homeostasis, thereby ameliorating intestinal barrier damage and reducing serum LPS and relevant inflammatory factor levels in the colon, serum, and DRG.

Abstract Background The aim of this study was to investigate the prognostic role of platelet to albumin ratio (PAR) and in persistent acute kidney injury (pAKI) of patients admitted to the intensive care unit (ICU). Methods We involved pAKI patients from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) database and eICU Collaborative Research Database (eICU-CRD). Receiver operating curve (ROC) analysis was performed to evaluate the optimal cut-off PAR. Results A total of 7,646 patients were finally included in the present study. The optimal cut-off value of PAR was 7.2. The high-PAR group was associated with pAKI (hazard ratio [HR]: 3.25, 95% CI: 2.85–3.72, P

Diabetic retinopathy (DR), a vision-threatening microvascular complication of diabetes mellitus (DM), is a leading cause of blindness worldwide that requires early detection and intervention. However, diagnosing DR early remains challenging due to the subtle nature of initial pathological changes. This review explores developments in multimodal imaging and functional tests for early DR detection. Where conventional color fundus photography is limited in the field of view and resolution, advanced quantitative analysis of retinal vessel traits such as retinal microvascular caliber, tortuosity, and fractal dimension (FD) can provide additional prognostic value. Optical coherence tomography (OCT) has also emerged as a reliable structural imaging tool for assessing retinal and choroidal neurodegenerative changes, which show potential as early DR biomarkers. Optical coherence tomography angiography (OCTA) enables the evaluation of vascular perfusion and the contours of the foveal avascular zone (FAZ), providing valuable insights into early retinal and choroidal vascular changes. Functional tests, including multifocal electroretinography (mfERG), visual evoked potential (VEP), multifocal pupillographic objective perimetry (mfPOP), microperimetry, and contrast sensitivity (CS), offer complementary data on early functional deficits in DR. More importantly, combining structural and functional imaging data may facilitate earlier detection of DR and targeted management strategies based on disease progression. Artificial intelligence (AI) techniques show promise for automated lesion detection, risk stratification, and biomarker discovery from various imaging data. Additionally, hematological parameters, such as neutrophil–lymphocyte ratio (NLR) and neutrophil extracellular traps (NETs), may be useful in predicting DR risk and progression. Although current methods can detect early DR, there is still a need for further research and development of reliable, cost-effective methods for large-scale screening and monitoring of individuals with DM.

The chalkiness, starch fine structure, and physiochemical properties of rice starch were analyzed and their correlations were investigated under different nighttime temperatures during the early grain-filling stage. Compared to MT, medium temperature (MT) and low (LNT) and high (HNT) nighttime temperatures resulted in an increased chalky grain rate (CGR) and chalkiness degree (CD). LNT mainly affected the chalkiness by increasing peak1 (short branch chains of amylopectin), the branching degree, and the proportion of small starch granules but decreasing peak2 (long branch chains of amylopectin) and peak3 (amylose branches). This altered the pasting properties, such as by increasing the peak viscosity and final viscosity. However, HNT mainly affected the chalkiness by increasing peak2 and the crystallinity degree but decreasing peak1 and peak3. Regarding the thermal properties, HNT also elevated peak and conclusion temperatures. The CGR and CD were significantly and positively correlated with the proportions of small and medium starch granules, peak1, branching degree, gelatinization enthalpy, setback viscosity, and pasting time but markedly and negatively correlated with the proportion of large starch granules, amylose content, peak3, peak viscosity, and breakdown viscosity. These findings suggest that LNT and HNT disrupted the starch structure, resulting in increased chalkiness. However, their mechanisms of action differ.

At present, clinical interventions for chronic kidney disease are very limited, and most patients rely on dialysis to sustain their lives for a long time. However, studies on the gut–kidney axis have shown that the gut microbiota is a potentially effective target for correcting or controlling chronic kidney disease. This study showed that berberine, a natural drug with low oral availability, significantly ameliorated chronic kidney disease by altering the composition of the gut microbiota and inhibiting the production of gut-derived uremic toxins, including p-cresol. Furthermore, berberine reduced the content of p-cresol sulfate in plasma mainly by lowering the abundance of g_Clostridium_sensu_stricto_1 and inhibiting the tyrosine–p-cresol pathway of the intestinal flora. Meanwhile, berberine increased the butyric acid producing bacteria and the butyric acid content in feces, while decreased the renal toxic trimethylamine N-oxide. These findings suggest that berberine may be a therapeutic drug with significant potential to ameliorate chronic kidney disease through the gut–kidney axis.

Abstract The controllable synthesis of complicated nanostructures in advanced two‐dimensional (2D) semiconductors, such as periodic regular hole arrays, is essential and remains immature. Here, we report a green, facile, highly controlled synthetic method to efficiently pattern 2D semiconductors, such as periodic regular hexagonal‐shaped hole arrays (HHA), in 2D‐TMDs. Combining the production of artificial defect arrays through laser irradiation with anisotropic annealing etching, we created HHA with different arrangements, controlled hole sizes, and densities in bilayer WS2. Atomic force microscopy (AFM), Raman, photoluminescence (PL), and scanning transmission electron microscopy (STEM) characterization show that the 2D semiconductors have high quality with atomical clean and sharp edges as well as undamaged crystals in the unetched region. Furthermore, other nanostructures, such as nanoribbons and periodic regular triangular‐shaped 2D‐TMD arrays, can be fabricated. This kind of 2D semiconductors fabrication strategy is general and can be extended to a series of 2D materials. Density functional theory (DFT) calculations show that one WS2 molecule from the edges of the laser‐irradiated holed region exhibits a robust etching activation, making selective etching at the artificial defects and the fabrication of regular 2D semiconductors possible.

Real-time and accurate detection of flame and smoke is an important prerequisite to reduce the loss caused by fire. There are exists some problems in traditional detection algorithms of flame and smoke, such as low accuracy, high miss rate, low detection efficiency, and low detection rate of small targets. This paper proposes the detection algorithm of flame and smoke based on ODConvBS in YOLOv5s. Firstly, the ordinary convolutional blocks in the backbone network of YOLOv5s are replaced with ODConvBS to achieve the extraction of attentional features from the convolutional kernel. Secondly, Gnconv is introduced into Neck to improve the high-order spatial information extraction ability of the model. Then, the Shuffle Attention module is added at the end of the Neck to facilitate the fusion of different groups of features. Finally, the prediction part uses a SIOU loss function that can take into account the angle of the prediction frame vectors to accelerate the model convergence. When utilizing the self-made dataset of flame and smoke, the upgraded YOLOv5s model mAP grew by 9.3%. At the same time, the accuracy rate, the recall rate, and the detection speed increased to 83.5%, 83.7%, 33.3FPS respectively.

A new structurally simple fluorescent CP probe based on chromone was designed and synthesized, and its structure was fully characterized using various analytical techniques. The CP probe displays a high selectivity and sensitivity for sensing Fe3+ with a “turn-off” fluorescence response over other metal ions in a DMSO/H2O (4:1, v/v) solution. The experiment results show that the CP probe is stable over a wide pH range of 2.0–12.0. The detection limit for Fe3+ was calculated to be 0.044 μmol•L−1. The molar ratio method indicated that the binding mode between the CP probe and Fe3+ is a 1:1 complex formation. HR-MS and density functional theory (DFT) calculations were also performed to further confirm the recognition mechanism. Both fluorescence imaging experiments and the MTT assay demonstrated that the CP probe was suitable for detecting intracellular Fe3+ and no significant cytotoxicity in living cells.

Ethylene, an important phytohormone, significantly influences plant growth and the ripeness of fruits and vegetables. During the transportation and storage of agricultural products, excessive ethylene can lead to economic losses due to rapid deterioration. Metal oxide semiconductor (MOS)-based chemo-resistive sensors are a promising technology for the detection of ethylene due to their low cost, high sensitivity, portability, etc. This review comprehensively summarizes the materials, fabrications, agricultural applications, and sensing mechanisms of these sensors. Moreover, the current challenges are highlighted and the potential solutions are proposed.

ABSTRACT: Moore's Law has been the driving force behind the semiconductor industry for several decades, but as silicon-based transistors approach their physical limits, researchers are searching for new materials to sustain this exponential growth. Two-dimensional transition metal dichalcogenides (TMDs), with their atomically thin structure and enticing physical properties, have emerged as the most promising candidates for downsizing and improving device integration. Emboldened by the direction of achieving large-area and high-quality TMDs growth, wafer-scale TMDs growth strategies have been continuously developed, suggesting that TMDs are poised to become a new platform for next-generation electronic devices. In this review, advanced synthesis routes and inherent properties of wafer-scale TMDs were critically assessed. In addition, the performance in electronic devices was also discussed, providing an outlook on the opportunities and challenges that lie ahead in their development.

IntroductionThe identification and localization of tea picking points is a prerequisite for achieving automatic picking of famous tea. However, due to the similarity in color between tea buds and young leaves and old leaves, it is difficult for the human eye to accurately identify them.MethodsTo address the problem of segmentation, detection, and localization of tea picking points in the complex environment of mechanical picking of famous tea, this paper proposes a new model called the MDY7-3PTB model, which combines the high-precision segmentation capability of DeepLabv3+ and the rapid detection capability of YOLOv7. This model achieves the process of segmentation first, followed by detection and finally localization of tea buds, resulting in accurate identification of the tea bud picking point. This model replaced the DeepLabv3+ feature extraction network with the more lightweight MobileNetV2 network to improve the model computation speed. In addition, multiple attention mechanisms (CBAM) were fused into the feature extraction and ASPP modules to further optimize model performance. Moreover, to address the problem of class imbalance in the dataset, the Focal Loss function was used to correct data imbalance and improve segmentation, detection, and positioning accuracy.Results and discussionThe MDY7-3PTB model achieved a mean intersection over union (mIoU) of 86.61%, a mean pixel accuracy (mPA) of 93.01%, and a mean recall (mRecall) of 91.78% on the tea bud segmentation dataset, which performed better than usual segmentation models such as PSPNet, Unet, and DeeplabV3+. In terms of tea bud picking point recognition and positioning, the model achieved a mean average precision (mAP) of 93.52%, a weighted average of precision and recall (F1 score) of 93.17%, a precision of 97.27%, and a recall of 89.41%. This model showed significant improvements in all aspects compared to existing mainstream YOLO series detection models, with strong versatility and robustness. This method eliminates the influence of the background and directly detects the tea bud picking points with almost no missed detections, providing accurate two-dimensional coordinates for the tea bud picking points, with a positioning precision of 96.41%. This provides a strong theoretical basis for future tea bud picking.

Background To assess in vivo confocal microscopy features of corneal sub-basal nerve plexus in patients with congenital or aponeurogenic blepharoptosis using a fully automated software (ACCMetrics). Patients and methods This prospective study included 33 patients with blepharoptosis and 17 normal controls. The corneal sub-basal nerve plexus was assessed using in vivo confocal microscopy, and the ocular surface status was evaluated by tear break-up times. Results The mean age of 33 patients with blepharoptosis and 17 normal controls were 38.77 ± 22.81 years and 48.35 ± 17.15 years, respectively. The mean duration of blepharoptosis was 16.42 ± 15.60 years. In 13 patients with unilateral blepharoptosis, there was no significant difference between affected eyes and contralateral eyes (all ps > .05), except for wider corneal nerve fibre width (CNFW) in affected eyes (0.024 ± 0.001 versus 0.023 ± 0.001 mm/mm2, p = .021). In 20 patients with bilateral blepharoptosis, there was no significant difference between the eyes. No significant difference was detected between 19 cases with congenital blepharoptosis and 14 cases with aponeurogenic blepharoptosis. When compared with normal controls, eyes with both unilateral and bilateral blepharoptosis had significantly wider CNFW. But from the point of aetiology, only eyes with congenital blepharoptosis presented with wider CNFW (p = .001), rather than the eyes with aponeurogenic blepharoptosis (p = .093). Besides, four young patients with congenital blepharoptosis revealed very sparse sub-basal nerve plexus. Conclusions These data suggested that corneal confocal microscopy demonstrated no significant changes in patients with blepharoptosis as compared with normal controls, except for relatively wider CNFW in congenital affected eyes. However, in some children and young adults with congenital blepharoptosis, the density of corneal sub-basal nerve plexus was evidently decreased, which needs to be cautioned when ones with congenital blepharoptosis want to take corneal surgeries or wear contact lens.Key messages When compared with normal controls, no significant effect was found in the influence of blepharoptosis on the most of corneal nerve parameters, except for corneal nerve fibre width (CNFW) in the group of congenital blepharoptosis. The age of onset of blepharoptosis may influence corneal nerve fibres, so timely surgical treatment of congenital blepharoptosis is not only conducive to the development of normal vision, but also beneficial to the reduction of corneal nerve lesions to some extent. We noted that some young blepharoptosis patients revealed sparse corneal nerve, which should be taken precaution when ones with congenital blepharoptosis who want to take corneal surgeries or wear contact lens.

Liver hepatocellular carcinoma (LIHC) is one of the most common malignant tumors, which is difficult to be diagnosed at an early stage due to its poor prognosis. Despite the fact that PANoptosis is important in the occurrence and development of tumors, no bioinformatic explanation related to PANoptosis in LIHC can be found. A bioinformatics analysis on the data of LIHC patients in TCGA database was carried out on the basis of previously identified PANoptosis-related genes (PRGs). LIHC patients were divided into two PRG clusters whose gene characteristics of differentially expressed genes (DEGs) were discussed. According to DEGs, the patients were further divided into two DEG clusters, and prognostic-related DEGs (PRDEGs) were applied to risk score calculation, the latter of which turned out to be practical in identifying the relationship among risk score, patient prognosis, and immune landscape. The results suggested that PRGs and relevant clusters were bound up with the survival and immunity of patients. Moreover, the prognostic value based on two PRDEGs was evaluated, the risk scoring model was constructed, and the nomogram model for predicting the survival rate of patients was further developed. Therefore, it was found that the prognosis of the high-risk subgroup was poor. Additionally, three factors, namely, the abundance of immune cells, the expression of immune checkpoints, and immunotherapy and chemotherapy were considered to be associated with the risk score. RT-qPCR results indicated higher positive expression of CD8A and CXCL6 in both LIHC tissues and most human liver cancer cell lines. In summary, the results suggested that PANoptosis was bound up with LIHC-related survival and immunity. Two PRDEGs were identified as potential markers. Thus, the understanding of PANoptosis in LIHC was enriched, with some strategies provided for the clinical therapy of LIHC.

Numerous studies have demonstrated that gut microbiota plays an important role in the development and treatment of different cardiovascular diseases, including hypertension, heart failure, myocardial infarction, arrhythmia, and atherosclerosis. Furthermore, evidence from recent studies has shown that gut microbiota contributes to the development of myocarditis. Myocarditis is an inflammatory disease that often results in myocardial damage. Myocarditis is a common cause of sudden cardiac death in young adults. The incidence of myocarditis and its associated dilated cardiomyopathy has been increasing yearly. Myocarditis has gained significant attention on social media due to its association with both COVID-19 and COVID-19 vaccinations. However, the current therapeutic options for myocarditis are limited. In addition, little is known about the potential therapeutic targets of myocarditis. In this study, we review (1) the evidence on the gut-heart axis, (2) the crosslink between gut microbiota and the immune system, (3) the association between myocarditis and the immune system, (4) the impact of gut microbiota and its metabolites on myocarditis, (5) current strategies for modulating gut microbiota, (6) challenges and future directions for targeted gut microbiota in the treatment of myocarditis. The approach of targeting the gut microbiota in myocarditis is still in its infancy, and this is the study to explore the gut microbiota-immune system-myocarditis axis. Our findings are expected to pave the way for the use of gut microbiota as a potential therapeutic target in the treatment of myocarditis.

Today, people around the world put more time and effort into exploring healthy foods and herbal medicines for improving health and disease prevention. Foods are expected to render physiological benefits beyond their traditionally nutritional value. An immense number of food components with medicinal activities beside nutrients have been found in various natural plants. Pouteria campechiana has been distributed throughout Central America, the Caribbean, some regions of Southeast Asia, and areas of Africa. Fruit of P. campechiana contains a broad spectrum of nutrients and plant bioactives. P. campechiana is utilized by local people as a useful medicinal resource for several therapeutic treatments. This paper provides a comprehensive review of P. campechiana from updated research literature. Botanical information, nutrient values, phytochemistry, as well as bioactivities are covered. The processes, proposals for product development, and toxicity of P. campechiana are also discussed.

Introduction: Alcoholic liver disease (ALD) is a leading cause of liver-related morbidity and mortality worldwide. However, there are no currently available drugs for ALD. Wangshi Baochi Pill (WBP) is a is a national confidential formulary of China, commonly used in clinical pediatrics to treat dyspepsia. In this study, we measured the therapeutic effect of WBP on ALD. Methods: The National Institute on Alcohol Abuse and Alcoholism (NIAAA) mouse model was used in our study. Experiments were performed to determine whether the hepatoprotective effect of WBP was associated with gut microbiota using a mixture of antibiotics (ABx). Gut flora was detected via full-length 16S rRNA sequencing on the Pacbio Sequel platform. Q-PCR and western blot were used to test lipid metabolism related genes. Results: WBP significantly reduced AST and ALT levels and alleviated liver damage. It also elevated hepatic alcohol-metabolizing enzymes (alcohol dehydrogenase and cytochrome P4502E1) activity. WBP down-regulated the FASN, CPT1-α, and CD36 and up-regulated PPAR-α. Moreover, we found WBP could alleviate ethanol-induced intestinal injury and inflammation. Our results suggest WBP was effective in attenuating hepatic steatosis and injury via intestinal flora, likely by elevating probiotics (B. pseudolongum PV8–2) and decreasing harmful bacteria. Discussions: Our study first suggested the therapeutic effect of WBP on ALD and provides a new approach for the treatment of ALD.

Pavement, as a kind of common public transit infrastructure, plays an important part in the daily passing and transportation-associated activities. The good conditions and smooth traffics of pavements matter significantly to the pavement users. However, due to long-time services, pavements often suffer from different kinds and severities of distresses, which might bring inconvenience to the pavement-related events, or even cause terrible traffic hazards. In this regard, we put forward a novel hybrid-window attentive vision transformer framework, called CrackFormer, for pavement crack detection aiming at providing an effective and automated solution to serving the pavement distress inspecting and repairing works. The CrackFormer employs a transformer-based high-resolution network architecture to rationally exploit and fuse multiscale feature semantics. To be specific, a hybrid-window based self-attention scheme is designed to extract feature semantics of entities both locally with dense windows and globally with sparse windows, which effectively improves the semantic details and accuracies. Moreover, a weighted multi-head self-attention philosophy is developed to recalibrate the contributions of different heads according to their relevance, which well enhances the feature encoding robustness and saliency. The CrackFormer is systematically tested on seven pavement crack detection datasets. Quantitative evaluations show that the CrackFormer achieves an overall performance with the precision of 0.9376, recall of 0.9352, and F1-score of 0.9364, respectively. In addition, qualitative examinations and comparative analyses all confirm the excellent performance of the CrackFormer for recognizing and delineating the pavement cracks of varying patterns under diverse pavement surface conditions.

Purpose: Left-right asymmetry, an important feature of brain development, has been implicated in neurodegenerative diseases, although it’s less discussed in typical Alzheimer’s disease (AD). We sought to investigate whether asymmetric tau deposition plays a potential role in AD heterogeneity. Methods: Two independent cohorts consisting of patients with mild cognitive impairment due to AD and AD dementia with tau PET imaging were enrolled [the Alzheimer’s Disease Neuroimaging Initiative (ADNI) cohort with 18F-Flortaucipir, the Shanghai Memory Study (SMS) cohort with 18F-Florzolotau]. Based on the absolute global tau interhemispheric differences, each cohort was divided into two groups (asymmetric versus symmetric tau distribution). The two groups were cross-sectionally compared in terms of demographic, cognitive characteristics, and pathological burden. The cognitive decline trajectories were analyzed longitudinally. Results: Fourteen (23.3%) and 42 (48.3%) patients in the ADNI and SMS cohorts showed an asymmetric tau distribution, respectively. An asymmetric tau distribution was associated with an earlier age at disease onset (proportion of early-onset AD: ADNI/SMS/combined cohorts, p = 0.093/0.026/0.001) and more severe pathological burden (i.e., global tau burden: ADNI/SMS cohorts, p

Aiming at solving the problems of bad imperceptibility and low embedding rate of existing algorithms, a novel large-capacity reversible image watermarking based on improved difference expansion (DE) is proposed. Firstly, the smoothness calculation algorithm is used to calculate and sort the smoothness values of the divided image sub-blocks; then, the scrambled watermark is embedded into the sub-blocks with less smoothness after removing the abrupt point by using the generalized difference expansion (GDE); finally, the absolute difference operation is applied to the generated overflow pixels to make their pixel values within a reasonable range for embedding watermark information. Under the premise of ensuring a certain visual quality, multiple watermark embedding can effectively improve the embedding rate. The simulation results show that this algorithm not only realizes blind extraction, but also recovers the original images without loss. At the same time, this algorithm achieves a high embedding rate (the average embedding rate is as high as 77.91 dB) without decreasing the visual quality.

Abstract The relationship between three scoring systems (LODS, OASIS, and SAPS II) and in-hospital mortality of intensive care patients with ST segment elevation myocardial infarction (STEMI) is currently inconclusive. The baseline data, LODS score, OASIS score, SAPS II score, and in-hospital prognosis of intensive care patients with STEMI were retrieved from the Medical Information Mart for Intensive Care IV database. Propensity score matching analysis was performed to reduce bias. Receiver operating characteristic curves (ROC) were drawn for the three scoring systems, and comparisons between the areas under the ROC curves (AUC) were conducted. Decision curve analysis (DCA) was performed to determine the net benefits of the three scoring systems. LODS and SAPS II were independent risk factors for in-hospital mortality. For the study cohort, the AUCs of LODS, OASIS, SAPS II were 0.867, 0.827, and 0.894; after PSM, the AUCs of LODS, OASIS, SAPS II were 0.877, 0.821, and 0.881. A stratified analysis of the patients who underwent percutaneous coronary intervention/coronary artery bypass grafting (PCI/CABG) or not was conducted. In the PCI/CABG group, the AUCs of LODS, OASIS, SAPS II were 0.853, 0.825, and 0.867, while in the non-PCI/CABG group, the AUCs of LODS, OASIS, SAPS II were 0.857, 0.804, and 0.897. The results of the Z test suggest that the predictive value of LODS and SAPS II was not statistically different, but both were higher than OASIS. According to the DCA, the net clinical benefit of LODS was the greatest. LODS and SAPS II have excellent predictive value, and in most cases, both were higher than OASIS. With a more concise composition and greater clinical benefit, LODS may be a better predictor of in-hospital mortality for intensive care patients with STEMI.

We report systematical zircon U–Pb datings, Hf isotopic data, major and trace element date on the Zhangshiying (ZSY) and the Taishanmiao (TSM) two plutons at the southern margin of the North China Craton (NCC), in order to investigate their petrogenesis and geological evolution. LA-ICP-MS U–Pb zircon of the ZSY and TSM granites dating yield a weighted mean 206Pb/238U age of 122.8 ± 1.5 Ma and 112.1 ± 3.2 Ma. The ZSY quartz syenite enriched in SiO2 (65.59–68.1 wt.%), Al2O3 (15.39–15.64 wt.%), high Sr (468–666 ppm), Sr/Y (35–45), (La/Yb)N (20.1–22.1) ratios, low Y(13.1–16.6 ppm), Yb (1.46–1.77 ppm), depleted in Nb, Ta, P, Ti, Mg, Y and negligible Eu anomalies, which suggesting that the quartz syenite are similar to adakitic rocks. Zircons from this pluton give εHf(t) values from −17.6 to −5.7 with an average of −15.2, and their TDM2 ages (1.29–1.91 Ga) are much younger than the basement rocks of the south margin of the NCC, which indicate that the ZSY quartz syenite were generated by partial melting of thickened lower crust with minor involvement of mantle-derived materials. The TSM pluton has characteristic of A-type granite, such as, high SiO2 (69.7–71.87 wt.%), total alkalis (Na2O + K2O = 8.5 to 9.41 wt.%), HFSE (Zr, Nb, Ga, Y), low CaO (0.27–1.25 wt.%), Ba, Sr and Eu. Their εHf(T) values ranges from −12.4 to −1.6 with an average of −7.6 and TDM2 ranges from 1.10 to 1.63 Ga with an average of 1.38 Ma. We propose that the TSM granites results from partial melting of tonalitic crustal sources with a plagioclase-rich residual at high temperatures and low pressure. Materials input from the mantle also is involved for the higher εHf(t) values than tonalitic crustal at the southern margin of NCC and high temperatures. Our results suggested that the thickened LCC at the south margin of the NCC is still existence before the intrusive of the ZSY adakitic rocks (∼123 Ma). During the intrusive of the TSM granites (∼112 Ma) it turns to extensional environment. This extensional event reflects the background of lithospheric thinning and decratonization of NCC.

Abstract Background Esophageal cancer is the fifth most common cancer affecting men in China. The primary treatment options are surgery and traditional radio-chemotherapy; no effective targeted therapy exists yet. Self-assembled RNA nanocarriers are highly stable, easily functionally modified, and have weak off-tumor targeting effects. Thus, they are among the most preferred carriers for mediating the targeted delivery of anti-tumor drugs. miR-375 was found to be significantly down-regulated in esophageal squamous cell carcinoma (ESCC) tissues and its overexpression effectively inhibits the proliferation, migration, and invasion of ESCC cells. Moreover, epidermal growth factor receptor (EGFR) was overexpressed in ESCC cells, and accumulation of RNA nanoparticles in ESCC tumors was enhanced by EGFR-specific aptamer (EGFRapt) modification. Results Herein, a novel four-way junction RNA nanocarrier, 4WJ-EGFRapt-miR-375-PTX simultaneously loaded with miR-375, PTX and decorated with EGFRapt, was developed. In vitro analysis demonstrated that 4WJ-EGFRapt-miR-375-PTX possesses strong thermal and pH stabilities. EGFRapt decoration facilitated tumor cell endocytosis and promoted deep penetration into 3D-ESCC spheroids. Xenograft mouse model for ESCC confirmed that 4WJ-EGFRapt-miR-375-PTX was selectively distributed in tumor sites via EGFRapt-mediating active targeting and targeted co-delivery of miR-375 and PTX exhibited more effective therapeutic efficacy with low systemic toxicity. Conclusion This strategy may provide a practical approach for targeted therapy of ESCC. Graphical Abstract

Abstract Background Long non-coding RNAs (lncRNAs) have been considered as one type of gene expression regulator for cancer development, but it is not clear how these are regulated. This study aimed to identify a specific lncRNA that promotes glioma progression. Methods RNA sequencing (RNA-seq) and quantitative real-time PCR were performed to screen differentially expressed genes. CCK-8, transwell migration, invasion assays, and a mouse xenograft model were performed to determine the functions of TMEM44-AS1. Co-IP, ChIP, Dual-luciferase reporter assays, RNA pulldown, and RNA immunoprecipitation assays were performed to study the molecular mechanism of TMEM44-AS1 and the downstream target. Results We identified a novel lncRNA TMEM44-AS1, which was aberrantly expressed in glioma tissues, and that increased TMEM44-AS1 expression was correlated with malignant progression and poor survival for patients with glioma. Expression of TMEM44-AS1 increased the proliferation, colony formation, migration, and invasion of glioma cells. Knockdown of TMEM44-AS1 in glioma cells reduced cell proliferation, colony formation, migration and invasion, and tumor growth in a nude mouse xenograft model. Mechanistically, TMEM44-AS1 is directly bound to the SerpinB3, and sequentially activated Myc and EGR1/IL-6 signaling; Myc transcriptionally induced TMEM44-AS1 and directly bound to the promoter and super-enhancer of TMEM44-AS1, thus forming a positive feedback loop with TMEM44-AS. Further studies demonstrated that Myc interacts with MED1 regulates the super-enhancer of TMEM44-AS1. More importantly, a novel small-molecule Myc inhibitor, Myci975, alleviated TMEM44-AS1-promoted the growth of glioma cells. Conclusions Our study implicates a crucial role of the TMEM44-AS1-Myc axis in glioma progression and provides a possible anti-glioma therapeutic agent.

Mutational activation of KRAS is a common oncogenic event in lung cancer, yet effective therapies are still lacking. Here, we identify B cell lymphoma 6 (BCL6) as a lynchpin in KRAS-driven lung cancer. BCL6 expression was increased upon KRAS activation in lung tumor tissue in mice and was positively correlated with the expression of KRAS-GTP, the active form of KRAS, in various human cancer cell lines. Moreover, BCL6 was highly expressed in human KRAS-mutant lung adenocarcinomas and was associated with poor patient survival. Mechanistically, the MAPK/ERK/ELK1 signaling axis downstream of mutant KRAS directly regulated BCL6 expression. BCL6 maintained the global expression of prereplication complex components; therefore, BCL6 inhibition induced stalling of the replication fork, leading to DNA damage and growth arrest in KRAS-mutant lung cancer cells. Importantly, BCL6-specific knockout in lungs significantly reduced the tumor burden and mortality in the LSL-KrasG12D/+ lung cancer mouse model. Likewise, pharmacological inhibition of BCL6 significantly impeded the growth of KRAS-mutant lung cancer cells both in vitro and in vivo. In summary, our findings reveal a crucial role of BCL6 in promoting KRAS-addicted lung cancer and suggest BCL6 as a therapeutic target for the treatment of this intractable disease.

For centuries, hunting and herding of large bovids were important for human survival at high altitudes on the Tibetan Plateau. However, little is known about past human relations with iconic plateau animals, such as takins (Budorcas taxicolor Hodgson, 1850) or yaks (Bos grunniens Linnaeus, 1766). Takins were widely hunted historically for subsistence and social reasons, but an understanding of ancient relationships has been hampered by the difficulty of distinguishing takins from other large wild or domestic bovids, e.g., gaurs (Bos gaurus), yaks, cattle (Bos taurus), water buffalo (Bubalus bubalis). Through the comparative and systematic study of modern specimens, comprising 80 mandibles and 53–78 skeletons curated across five institutions in China and the United States, this research proposes a new set of osteomorphological criteria for differentiating large bovids from the Tibetan Plateau and tests previously published criteria. The results show that takins can be easily differentiated from yaks, cattle, gaurs, and water buffalos using readily identifiable shape differences, non-metric characteristics, and specific landmarks of mandibular teeth and post-cranial elements. Criteria with especially high-reliability scores include mandibular teeth and 14 postcranial elements: scapula, humerus, femur, tibia, fibula, metapodials, lunate, scaphoid, magnum, unciform, and astragalus. Providing a reproducible field method for distinguishing takins from other large bovids in this region, the osteomorphological criteria established in this study will further archaeological investigations of Holocene hunting on the Tibetan Plateau, as well as early usage of domesticated yaks and cattle. These criteria can also be used in conservation to aid field identification of illegally hunted takins.

BackgroundEndoscopic submucosal dissection (ESD) has been accepted as the standard treatment for the appropriate indication of early gastric cancer (EGC). Determining the risk of lymph node metastasis (LNM) is critical for the following treatment selection after ESD. This study aimed to develop a predictive model to quantify the probability of LNM in EGC to help minimize the invasive procedures.MethodsA total of 952 patients with EGC who underwent radical gastrectomy were retrospectively reviewed. LASSO regression was used to help screen the potential risk factors. Multivariate logistic regression was used to establish a predictive nomogram, which was subjected to discrimination and calibration evaluation, bootstrapping internal validation, and decision curve analysis.ResultsResults of multivariate analyses revealed that gender, fecal occult blood test, CEA, CA19-9, histologic differentiation grade, lymphovascular invasion, depth of infiltration, and Ki67 labeling index were independent prognostic factors for LNM. The nomogram had good discriminatory performance, with a concordance index of 0.816 (95% CI 0.781–0.853). The validation dataset yielded a corrected concordance index of 0.805 (95% CI 0.770–0.842). High agreements between ideal curves and calibration curves were observed.ConclusionsThe nomogram is clinically useful for predicting LNM after ESD in EGC, which is beneficial to identifying patients who are at low risk for LNM and would benefit from avoiding an unnecessary gastrectomy.

Abstract Tumor cells require high levels of cholesterol for membrane biogenesis for rapid proliferation during development. Beyond the acquired cholesterol from low-density lipoprotein (LDL) taken up from circulation, tumor cells can also biosynthesize cholesterol. The molecular mechanism underlying cholesterol anabolism in esophageal squamous cell carcinoma (ESCC) and its effect on patient prognosis are unclear. Dysregulation of lipid metabolism is common in cancer. Lysophosphatidylcholine acyltransferase 1 (LPCAT1) has been implicated in various cancer types; however, its role in esophageal squamous cell carcinoma (ESCC) remains unclear. In this study, we identified that LPCAT1 is highly expressed in ESCC and that LPCAT1 reprograms cholesterol metabolism in ESCC. LPCAT1 expression was negatively correlated with patient prognosis. Cholesterol synthesis in ESCC cells was significantly inhibited following LPCAT1 knockdown; cell proliferation, invasion, and migration were significantly reduced, along with the growth of xenograft subcutaneous tumors. LPCAT1 could regulate the expression of the cholesterol synthesis enzyme, SQLE, by promoting the activation of PI3K, thereby regulating the entry of SP1/SREBPF2 into the nucleus. LPCAT1 also activates EGFR leading to the downregulation of INSIG-1 expression, facilitating the entry of SREBP-1 into the nucleus to promote cholesterol synthesis. Taken together, LPCAT1 reprograms tumor cell cholesterol metabolism in ESCC and can be used as a potential treatment target against ESCC.

Objective: Nonalcoholic fatty liver disease (NAFLD) is a serious threat to human health worldwide. In this study, the aim is to analyze diagnosis biomarkers in NAFLD and its relationship with the immune microenvironment based on bioinformatics analysis.Methods: We downloaded microarray datasets (GSE48452 and GSE63067) from the Gene Expression Omnibus (GEO) database for screening differentially expressed genes (DEGs). The hub genes were screened by a series of machine learning analyses, such as support vector machine (SVM), least absolute shrinkage and selection operator (LASSO), and weighted gene co-expression network analysis (WGCNA). It is worth mentioning that we used the gene enrichment analysis to explore the driver pathways of NAFLD occurrence. Subsequently, the aforementioned genes were validated by external datasets (GSE66676). Moreover, the CIBERSORT algorithm was used to estimate the proportion of different types of immune cells. Finally, the Spearman analysis was used to verify the relationship between hub genes and immune cells.Results: Hub genes (CAMK1D, CENPV, and TRHDE) were identified. In addition, we found that the pathogenesis of NAFLD is mainly related to nutrient metabolism and the immune system. In correlation analysis, CENPV expression had a strong negative correlation with resting memory CD4 T cells, and TRHDE expression had a strong positive correlation with naive B cells.Conclusion: CAMK1D, CENPV, and TRHDE play regulatory roles in NAFLD. In particular, CENPV and TRHDE may regulate the immune microenvironment by mediating resting memory CD4 T cells and naive B cells, respectively, and thus influence disease progression.

Background: Intestinal tumors are the third most common malignant tumors worldwide, accounting for approximately 10% of all new cancer cases worldwide. Cancer prevention is a promising way to limit the intestinal tumor incidence rate; however, challenges remain. Qingchang Wenzhong decoction (QCWZD) can clinically treat mild to moderate ulcerative colitis symptoms. Moreover, the mechanism by which it prevents intestinal tumors has not been clarified. In this study, we explored the mechanism by which QCWZD prevents the occurrence of intestinal tumors.Methods: To study the preventive mechanism of QCWZD on intestinal tumors, we used two model mice with azoxymethane/dextran sodium sulfate (AOM/DSS)- and Apcmin/+-induced intestinal tumor formation. The two models exhibited colitis-associated cancer and familial adenomatous polyposis, respectively. Colon and small intestine tissues were collected and analyzed based on histopathology and immunohistochemistry analyses. Fecal samples were collected, and 16S rRNA sequencing was used to analyze the correlation between intestinal microbiota and the prevention of intestinal tumors.Results: In the AOM/DSS mice, the QCWZD reduced the number and size of tumors, as well as tumor load. Similarly, in the Apcmin/+ mice, QCWZD can also reduce the number of tumors and the tumor load. The results of 16S rRNA sequencing confirmed that QCWZD altered the composition of intestinal microbiota in mice, a phenomenon that may prevent the occurrence of intestinal tumors by aiding the increase in the abundance of beneficial bacteria, such as Ralstonia and Butyricicoccus, and reducing that of pathogenic bacteria, such as Desulfobacterota and Bacteroides, in the intestine. Further, immunohistochemistry reveald that QCWZD can improve the expression of intestinal barrier-related proteins and inhibit pyroptosis-related proteins.Conclusions: QCWZD has the potential to prevent the occurrence of intestinal tumors. The anti-tumor activity may be achieved by regulating the intestinal microbiota, improving the function of the intestinal barrier, and inhibiting GSDME mediated pyroptosis.

Heat stress during the grain-filling stage seriously affects grain quality in rice. However, very limited information is available regarding the effects of short-term high nighttime temperature (HNT) on grain chalkiness formation in rice. In this paper, the effects of HNT at the early grain-filling stage (7 days after ear emergence) on rice chalkiness formation and the potential causes were investigated by using two rice varieties that differed in susceptibility to high temperature. Although the HNT treatment at night dramatically increased the grain chalkiness in Jiuxiangzhan (JXZ) and Huanghuazhan (HHZ), the increase was greater in JXZ compared to HHZ. The net photosynthetic rate and SPAD value were significantly reduced by HNT treatment in the flag leaves of JXZ, while no significant differences were observed in HHZ. Furthermore, HNT treatment reduced the antioxidant enzyme activity in the flag leaves of JXZ, while the opposite was observed in HHZ, exhibiting increased antioxidant enzyme activity. Moreover, HNT treatment altered the endogenous hormone levels, enhanced the enzymatic activities related to starch biosynthesis, and accelerated the filling rate in grains of JXZ when compared to HHZ. Scanning electron microscopy (SEM) observation exhibited that the starch granules in the endosperm of JXZ were loosely packed together and more starch granules with small pits were produced after HNT treatment. Based on these data, we inferred that HNT stress during the early stage of rice grain filling accelerated the grain-filling rate but shortened the grain-filling duration by changing the endogenous hormone levels and enhancing the enzymatic activities responsible for starch biosynthesis, resulting in significant changes in the morphological structure and arrangement of starch granules and eventually causing the occurrence of grain chalkiness.

In the western Kunlun Mountain region, due to the convergence of the Paleotethys Ocean in the Late Paleozoic, through northward subduction towards the West Kunlun Block, forming the Kangxiwa–Waqia arc magmatism and back-arc extensional basins, including the Tamu–Kalangu and Oytag–Kurliang basins. This study explores the relationship between basin evolution and mineralization. First, the Late Paleozoic back-arc and far-field continental back-arc basins were distinguished by analyzing sediment constructions in the basins. The former was continuously deposited in the Middle Devonian–Late Permian above the Precambrian basement due to the existence of the depressions. The latter were intermittently deposited in the Middle Devonian–Late Permian due to rifting above the Caledonian orogenic belt. Although the two settings were separated by the Tiekelike fault, their formations were subject to mantle upwelling caused by the subduction of the Kangxiwa oceanic crust. We also divided the Hercynian and Indosinian magmatic activities related to the basin; the former of which included the formation of bimodal magmatic rocks (339–291 Ma) as the basin expanded, which resulted in hydrothermal sediments and hydrothermal–magmatic mineralization, mainly including volcanic massive copper sulfide, Cu and Ni sulfide, and hydrothermal deposits. During the Indosinian orogeny, intermediate acidic magmatic rocks (265–206 Ma) associated with the closure of the basin was formed, leading to the development of hydrothermal Cu–polymetallic and porphyritic copper deposits. The relationship between basin evolution and mineralization was determined. Based on the findings, we concluded that the basin extended between the Middle Devonian and Early Permian. Syngenetic sedimentary deposits formed in the closed basins and anoxic environments of local depressions and mainly included sedimentary rock-hosted stratiform Cu deposits, exhalation-sedimentary Pb–Zn deposits, and sedimentary Mn deposits. Between the Middle Permian and Early Triassic, the basin began to close and the transformation from a basin to a mountain range finally occurred. The sedimentary basement was transformed by folding and faulting, thus forming tectonic deposits, including hydrothermal vein-type Pb–Zn deposits and Cu–Pb deposits within tectonically altered rocks. The results of this work show that the Late Paleozoic extensional tectonic environment formed both the back-arc basin and the far-field continental basin simultaneously. Periods of magmatism related to rifting and convergence could be distinguished by the corresponding mineralization. The metallogenic types related to the basin could also be divided into sedimentary, magmatic hydrothermal and tectonic hydrothermal deposits.

Background: Periodontitis is associated with periodontal tissue damage and teeth loss. Nonalcoholic fatty liver disease (NAFLD) has an intimate relationship with periodontitis. Nevertheless, interacted mechanisms between them have not been clear. This study was intended for the exploration of shared gene signatures and latent therapeutic targets in periodontitis and NAFLD.Methods: Microarray datasets of periodontitis and NAFLD were obtained from the Gene Expression Omnibus (GEO) database. The weighted gene co-expression network analysis (WGCNA) was utilized for the acquisition of modules bound up with NAFLD and periodontitis. We used ClueGO to carry out biological analysis on shared genes to search their latent effects in NAFLD and periodontitis. Another cohort composed of differential gene analysis verified the results. The common microRNAs (miRNAs) in NAFLD and periodontitis were acquired in the light of the Human microRNA Disease Database (HMDD). According to miRTarbase, miRDB, and Targetscan databases, latent target genes of miRNAs were forecasted. Finally, the miRNAs–mRNAs network was designed.Results: Significant modules with periodontitis and NAFLD were obtained via WGCNA. GO enrichment analysis with GlueGo indicated that damaged migration of dendritic cells (DCs) might be a common pathophysiologic feature of NAFLD and periodontitis. In addition, we revealed common genes in NAFLD and periodontitis, including IGK, IGLJ3, IGHM, MME, SELL, ENPP2, VCAN, LCP1, IGHD, FCGR2C, ALOX5AP, IGJ, MMP9, FABP4, IL32, HBB, FMO1, ALPK2, PLA2G7, MNDA, HLA-DRA, and SLC16A7. The results of differential analysis in another cohort were highly accordant with the findings of WGCNA. We established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis. Finally, the analysis of miRNA pointed out that hsa-mir-125b-5p, hsa-mir-17-5p, and hsa-mir-21-5p might provide potential therapeutic targets.Conclusion: Our study initially established a comorbidity model to explain the underlying mechanism of NAFLD secondary to periodontitis, found that damaged migration of DCs might be a common pathophysiological feature of NAFLD and periodontitis, and provided potential therapeutic targets.

Abstract The two‐dimensional (2D) in‐plane (lateral) heterostructures have attracted increasing interest for potential applications in the atomically thin electronics and optoelectronics. While most studies focus on semiconductor‐semiconductor lateral heterostructures with highly similar lattice structures between the constituent components, the synthesis of metal‐semiconductor lateral heterostructures is much less explored and usually more challenging due to more distinct lattice structures or chemical properties. Herein, a vapor phase epitaxy growth method of high‐quality metal‐semiconductor lateral heterostructures between tetragonal CoSe and hexagonal WSe2 is reported. The 2D CoSe can selectively nucleate at the edge of pre‐grown WSe2 nanosheets to form CoSe‐WSe2 metal‐semiconductor lateral heterostructures. Optical microscopy (OM), scanning electron microscopy (SEM), and atomic force microscopy (AFM) studies reveal distinct contrast across the heterostructure interface. High‐resolution transmission electron microscopy (HRTEM) and selected area electron diffraction (SAED) studies further confirm the microstructure modulation across the heterostructure interface. The field‐effect transistors (FETs) of CoSe‐WSe2 lateral heterostructures show satisfactory Ohmic contacts and considerably better FET performance over those with deposited Cr/Au contacts, suggesting the in‐plane metal‐semiconductor junctions may function as improved contacts for the atomically thin electronics.

Abstract Background PR55α plays important roles in oncogenesis and progression of numerous malignancies. However, its role in hepatocellular carcinoma (HCC) is unclear. This study aims to characterize the functions of PR55α in HCC. Methods PR55α expressions in HCC tissues and paired healthy liver samples were evaluated using Western blot and tissue microarray immunohistochemistry. We knocked down the expression of PR55α in SMMC-7721 and LM3 cell lines via small interfering and lentivirus. In vitro cell counting, colony formation, migration and invasion assays were performed along with in vivo xenograft implantation and lung metastases experiments. The potential mechanisms involving target signal pathways were investigated by RNA-sequencing. Results PR55α expression level was suppressed in HCC tissues in comparison to healthy liver samples. Decreased PR55α levels were correlated with poorer prognosis (P = 0.0059). Knockdown of PR55α significantly promoted cell proliferation and migration, induced repression of the cell cycle progression and apoptosis in vitro while accelerating in vivo HCC growth and metastasis. Mechanistic analysis indicated that PR55α silencing was involved with MAPK/AKT signal pathway activation and resulted in increased phosphorylation of both AKT and ERK1/2. Conclusions This study identifies PR55α to be a candidate novel therapeutic target in the treatment of HCC.

AbstractObjective To use optical coherence tomography (OCT) to compare retinal biomarkers of choroidal neovascularization (CNV) secondary to multifocal choroiditis (MFC), myopic choroidal neovascularization (mCNV), and idiopathic choroidal neovascularization (ICNV) and to provide a basis for its clinical diagnosis and treatment.Methods In this retrospective case study, patients admitted to the Second Hospital of Hebei Medical University between January 2018 and January 2021 who were initially diagnosed with CNV secondary to MFC, mCNV, and ICNV were categorized into groups, by disease, for analysis. Spectral domain-OCT (SD-OCT) was used to describe and measure the morphological characteristics of CNV lesions in each group. The retinal biomarkers of CNV in MFC, mCNV, and ICNV were compared.Results Sixty-eight patients (71 eyes) were included and all eyes were diagnosed with active type 2 CNV. The MFC group had higher refraction than the ICNV group (P2 0.05).Conclusions OCT biomarkers, such as the diameter of the CNV, SRF, the “pitchfork sign,” and CT under CNV are useful in distinguishing CNV secondary to MFC from mCNV, which can allow the timely selection of treatment in some difficult cases. There were no differences between the MFC group and ICNV group except in refractive error, which indicates that some ICNV cases may be an early stage of a type of occult chorioretinitis. Long-term follow-up is needed for ICNV patients to confirm whether there is any potential inflammation.Key messagesSometimes, it is difficult to separate MFC with CNV from myopic CNV and ICNV in clinical.OCT biomarkers, such as the diameter of the CNV, SRF, the “pitchfork sign,” and CT under CNV are useful in distinguishing CNV secondary to MFC from mCNV.There were no differences between the MFC group and ICNV group except in refractive error.

An optimization design of the bending-vibration resistance of magnetorheological elastomer carbon fibre reinforced polymer sandwich sheets (MECFRPSSs) was studied in this paper. Initially, by adopting the classical laminate theory, the Reddy’s high-order shear deformation theory, the Rayleigh-Ritz method, etc., an analytical model of the MECFRPSSs was established to predict both bending and vibration parameters, with the three-point bending forces and a pulse load being considered separately. After the validation of the model was completed, the optimization design work of the MECFRPSSs was conducted based on an optimization model developed, in which the thickness, modulus, and density ratios of magnetorheological elastomer core to carbon fibre reinforced polymer were taken as design variables, and static bending stiffness, the averaged damping, and dynamic stiffness parameters were chosen as objective functions. Subsequently, an artificial bee colony algorithm was adopted to execute single-objective, dual-objective, and multi-objective optimizations to obtain the optimal design parameters of such structures, with the convergence effectiveness being examined in a validation example. It was found that it was hard to improve the bending, damping, and dynamic stiffness behaviours of the structure simultaneously as the values of design variables increased. Some compromised results of design parameters need to be determined, which are based on Pareto-optimal solutions. In further engineering application of the MECFRPSSs, it is suggested to use the corresponding design parameters related to a turning point to better exert their bending-vibration resistance.

The DFT method is employed to study the adsorption and reaction behaviors of HC2O4−, H2PO4−, HSO4− and H2O on neutral and anodic aluminum slabs. With the exception of adsorption, the three acid radicals can successively take the two H atoms from the adsorbed H2O on the anodic aluminum slabs, which is the key step of the formation of anodic alumina. The dehydrogenation reaction is dominated by the Coulombic interaction of O and H, respectively belonging to acid radicals and the adsorbed H2O or OH, rather than by the interaction of electronic orbits located on the two kinds of atoms. The experiment of anodic polarization of aluminum verifies the calculation result well.