Heterojunction polarization enhancement and shielding for AlGaN-based solar-blind ultraviolet avalanche detectors.

AlGaN-based solar-blind ultraviolet avalanche detectors have huge potentials in the fields of corona discharge monitoring, biological imaging, etc. Here, we study the impact of the heterojunction polarization-related effects on the AlGaN-based solar-blind ultraviolet avalanche detectors. Our work confirms that the polarization heterojunction is beneficial to reducing avalanche bias and lifting avalanche gain by improving the electric field in the depletion region, while the polarization-induced fixed charges will lead to a redistribution of the electrons, in turn shielding the charges and weakening the electric field enhancement effect. This shielding effect will need external bias to eliminate, and that is why the polarization heterojunction cannot work at relatively low bias but has an enhancement effect at high bias. Controlling the doping level between the hetero-interface can affect the shielding effect. An unintentionally doped polarization heterojunction can effectively reduce the shielding effect, thus reducing the avalanche bias. The conclusions also hold true for the negative polarization regime. We believe our findings can provide some useful insights for the design of the AlGaN-based solar-blind ultraviolet detectors.

Harnessing the Lysosomal Sorting Signals of the Cation-Independent Mannose-6-Phosphate Receptor for Targeted Degradation of Membrane Proteins.

Membrane proteins are a crucial class of therapeutic targets that remain challenging to modulate using traditional occupancy-driven inhibition strategies or current proteolysis-targeting degradation approaches. Here, we report that the inherent endolysosomal sorting machinery can be harnessed for the targeted degradation of membrane proteins. A new degradation technique, termed signal-mediated lysosome-targeting chimeras (SignalTACs), was developed by genetically fusing the signaling motif from the cation-independent mannose-6-phosphate receptor (CI-M6PR) to a membrane protein binder. Antibody-based SignalTACs were constructed with the CI-M6PR signal peptides fused to the C-terminus of both heavy and light chains of IgG. We demonstrated the scope of this platform technology by degrading five pathogenesis-related membrane proteins, including HER2, EGFR, PD-L1, CD20, and CD71. Furthermore, two simplified constructs of SignalTACs, nanobody-based and peptide-based SignalTACs, were created and shown to promote the lysosomal degradation of target membrane proteins. Compared to the parent antibodies, SignalTACs exhibited significantly higher efficiency in inhibiting tumor cell growth both in vitro and in vivo. This work provides a simple, general, and robust strategy for degrading membrane proteins with molecular precision and may represent a powerful platform with broad research and therapeutic applications.

Peripherin: A proposed biomarker of traumatic axonal injury triggered by mechanical force.

Traumatic axonal injury (TAI) is one of the most common pathological features of severe traumatic brain injury (TBI). Our previous study using proteomics suggested that peripherin (PRPH) should be a potential candidate as a biomarker for TAI diagnosis. This study is to further elucidate the role and association of PRPH with TAI. In the animal study, we performed immunohistochemistry, ELISA and morphological analysis to evaluate PRPH level and distribution following a severe impact. PRPH-positive regions were widely distributed in the axonal tract throughout the whole brain. Axonal injuries with PRPH inclusion were observed post-TBI. Besides, PRPH was significantly increased in both cerebral spinal fluid and plasma at the early phase post-TBI. Colocalization analysis based on microscopy revealed that PRPH represents an immunohistological biomarker in the neuropathological diagnosis of TAI. Brain samples from patients with TBI were included to further test whether PRPH is feasible in the real practice of neuropathology. Immunohistochemistry of PRPH, NFH, APP and NFL on human brain tissues further confirmed PRPH as an immunohistological biomarker that could be applied in practice. Collectively, we conclude that PRPH mirrors the cytoskeleton injury of axons and could represent a neuropathological biomarker for TAI.

Indole-Based Long-Wavelength Fluorescent Probes for Bioimaging of S-Nitrosylation in Mitochondria.

S-Nitrosylation has been found to play an important role in regulating mitochondrial function. However, probes for detection of protein S-nitrosylation in mitochondria remain unexplored. Herein, a novel 4-(pyridin-4-yl)vinyl-substituted indole was designed, exhibiting a long-wavelength emission and a high fluorescent quantum yield. Functionalization of the 7-position of the indole ring with an arylphosphine ester resulted with probes with efficient mitochondria-targeting ability. Furthermore, the indole-arylphosphine displayed a significant fluorescence enhancement upon exposure to S-nitrosoglutathione (GSNO) at low micromolar concentrations in A431 cells. Taken together, this study provides a new indole-based fluorescent probe with a unique long-wavelength emission for direct detection of S-nitrosylation in mitochondria, which may represent a powerful tool for understanding the critical roles of S-nitrosylation within mitochondria of living organisms.

Strategies for efficient production of recombinant proteins in Escherichia coli: alleviating the host burden and enhancing protein activity.

Escherichia coli, one of the most efficient expression hosts for recombinant proteins (RPs), is widely used in chemical, medical, food and other industries. However, conventional expression strains are unable to effectively express proteins with complex structures or toxicity. The key to solving this problem is to alleviate the host burden associated with protein overproduction and to enhance the ability to accurately fold and modify RPs at high expression levels. Here, we summarize the recently developed optimization strategies for the high-level production of RPs from the two aspects of host burden and protein activity. The aim is to maximize the ability of researchers to quickly select an appropriate optimization strategy for improving the production of RPs.

Developing a dynamic equilibrium system in Escherichia coli to improve the production of recombinant proteins.

The combination of Escherichia coli BL21 (DE3) and the pET expression system is used extensively for the expression of various recombinant proteins (RPs). However, RP overexpression often introduces a growth burden for the host, especially in the case of toxic proteins. The key to solving this problem is to reduce the host burden associated with protein overproduction, which is often achieved by regulating the expression or activity of T7 RNAP or growth-decoupled systems. However, these strategies mainly relieve or interrupt the robbing of host resources, and do not eliminate other types of host burdens in the production process. In this study, we constructed a production system based on a dynamic equilibrium to precisely relieve the host burden and increase the RP production. The system is composed of three modules, including the overexpression of basic growth-related genes (rRNA, RNAP core enzyme, sigma factors), prediction and overexpression of key proteins using the enzyme-constrained model ec_iECBD_1354, and dynamic regulation of growth-related and key protein expression intensity based on a burden-driven promoter. Using this system, the production of many high-burden proteins, including autolysis protein and E. coli membrane proteins, was increased to varying degrees. Among them, the cytosine transporter protein (CodB) was most significantly improved, with a 4.02-fold higher production compared to the wild strain. This system can effectively reduce the optimizing costs, and is suitable for developing various types of RP expression hosts rapidly. KEY POINTS: • The basic growth-related resources can relieve the host burden from recombinant protein. • The enzyme-constrained model can accurately predict key genes to improve yield. • The expression intensity can be dynamically adjusted with changes in burden.

Saringosterol Acetate Isolated from Sargassum fusiformis Induces Mitochondrial-Mediated Apoptosis in MCF-7 Breast Cancer Cells.

Sargassum fusiformis is among the most important edible brown seaweeds in Eastern Asia that contains various bioactive compounds and strong activities. Saringosterol acetate (SA) was successfully isolated from S. fusiformis in our previous research. In this study, SA was investigated for its anticancer effect on MCF-7 breast cancer cells. SA attenuated the survival rate of MCF-7 cells with an IC50 value of 63.16±3.6 µg/mL. Staining with Hoechst 33342 demonstrated that SA treatment mediated apoptotic body generation. SA significantly downregulated Bcl-xL and upregulated Bax, and cleaved PARP, and cleaved caspase 3 in a dose-dependent manner. Thus, these results suggest that SA induced mitochondria-mediated apoptosis in MCF-7 cells, making it a plausible candidate for drug development against breast cancer.

Treatment of Obese Zebrafish with Saringosterol Acetate through AMP Activated Protein Kinase Pathway.

OBJECT: Edible Brown Seaweed Sargassum fusiforme (Harvey) Setchell, 1931 abbreviated as Sargassum fusiforme was used for folk medical therapy in East Asia countries over five hundred years. Saringosterol acetate (SA) was isolated from S. fusiforme in our previous study and indicated various effects. However, anti-obesity activity of SA and its mechanism still unknown. METHOD: The inhibitory effect of SA, isolated from S. fusiforme, on adipogenesis in 3T3-L1 adipocytes was investigated in vitro and in zebrafish model. Cell toxicity, differentiation, signaling pathway, and lipid accumulation of SA treated 3T3-L1 adipocytes were determined. The body weight and triglyceride content of diet-induced obese (DIO) adult male zebrafish were measured from 12 to 17 weeks after fertilization. RESULT: SA attenuated the differentiation of cells and reduced lipid accumulation, and triglyceride content in the 3T3-L1 adipocytes. During the differentiation of adipocytes, SA suppressed fat accumulation and decreased the expression of signal factors responsible for adipogenesis. In SA-treated adipocytes, while fatty acid synthetase was downregulated, AMP-activated protein kinase (AMPK) was upregulated. Furthermore, SA suppressed body weight and triglyceride content in DIO zebrafish. CONCLUSION: SA is a potential therapeutic agent in the management of metabolic disorders, such as obesity.

Diagnosis of Esophageal Lesions by Multi-Classification and Segmentation Using an Improved Multi-Task Deep Learning Model.

It is challenging for endoscopists to accurately detect esophageal lesions during gastrointestinal endoscopic screening due to visual similarities among different lesions in terms of shape, size, and texture among patients. Additionally, endoscopists are busy fighting esophageal lesions every day, hence the need to develop a computer-aided diagnostic tool to classify and segment the lesions at endoscopic images to reduce their burden. Therefore, we propose a multi-task classification and segmentation (MTCS) model, including the Esophageal Lesions Classification Network (ELCNet) and Esophageal Lesions Segmentation Network (ELSNet). The ELCNet was used to classify types of esophageal lesions, and the ELSNet was used to identify lesion regions. We created a dataset by collecting 805 esophageal images from 255 patients and 198 images from 64 patients to train and evaluate the MTCS model. Compared with other methods, the proposed not only achieved a high accuracy (93.43%) in classification but achieved a dice similarity coefficient (77.84%) in segmentation. In conclusion, the MTCS model can boost the performance of endoscopists in the detection of esophageal lesions as it can accurately multi-classify and segment the lesions and is a potential assistant for endoscopists to reduce the risk of oversight.

Comparison of Dechlorane Plus Concentrations in Sequential Blood Samples of Pregnant Women in Taizhou, China.

To develop an appropriate sampling strategy to assess the intrauterine exposure to dechlorane plus (DP), we investigated DP levels in sequential maternal blood samples collected in three trimesters of pregnancy, respectively, from women living in Taizhou. The median concentration of DPs (sum of syn-DP and anti-DP) in all samples was 30.5 pg g−1 wet-weight and 5.01 ng g−1 lipid-adjusted weight, respectively. The trimester-related DP concentrations were consistently strongly correlated (p < 0.01), indicating that a single measurement of DP levels could represent intrauterine exposure without sampling from the same female repeatedly; however, the wet-weight levels significantly increased across trimesters (p < 0.05), while the lipid-adjusted levels did not significantly vary. Notably, whether lipid-adjusted weight or wet-weight levels, the variation extent of DP across trimesters was found to be less than 41%, and those for other persistent organic pollutants (POPs) reported in the literature were also limited to 100%. The limitation in variation extents indicated that, regardless of the time of blood collection during pregnancy and how the levels were expressed, a single measurement could be extended to screen for exposure risk if necessary. Our study provides different strategies for sampling the maternal blood to serve the requirement for assessment of in utero exposure to DP.

UBE2S exerts oncogenic activities in urinary bladder cancer by ubiquitinating TSC1.

Ubiquitin-conjugating enzyme E2S (UBE2S), an important E2 enzyme in the process of ubiquitination, has exhibited oncogenic activities in various malignant tumors. However, it remains unknown whether UBE2S plays a role in urinary bladder cancer (UBC) development. In the current study, our data confirmed UBE2S upregulation in UBC. In vitro and in vivo experiments demonstrated that UBE2S knockdown resulted in attenuated proliferation and enhanced apoptosis, which was inverse to the phenotypes with UBE2S overexpression. Gain and loss of function assays confirmed that UBE2S exerts oncogenic activities in UBC by mediating the activation of the mammalian target of rapamycin complex 1 (mTORC1) pathway. Furthermore, we discovered that this UBE2S-modulated carcinogenic mechanism was in the consequence of directly targeting tuberous sclerosis 1 (TSC1), which is the upstream inhibitor of mTOR signaling for ubiquitous degradation. Taken together, this study demonstrated that UBE2S is a carcinogen in UBC and promotes UBC progression by ubiquitously degrading TSC1. This consequently mediates the activation of the mTOR pathway, suggesting a potential therapeutic regimen for UBC by targeting the newly identified UBE2S/TSC1/mTOR axis.

Biotransformation of Ginsenosides (Rb1 , Rb2 , Rb3 , Rc) in Human Intestinal Bacteria and Its Effect on Intestinal Flora.

Ginsenosides, including Rb1 , Rb2 , Rb3 and Rc, belong to protopanaxadiol-type saponins in Panax ginseng C. A. Mey. Their contents are high in P. ginseng. They could inhibit oxidant stress, enhance immunity, lower blood sugar, resist tumor cells and facilitate other physiological activities. This study aimed to explore the interaction between ginsenosides Rb1 , Rb2 , Rb3 and Rc and the intestinal flora of healthy people. It also sought to analyse the biotransformation products and pathways of these ginsenosides in in-vitro human intestinal bacteria and their effects on the diversity of human intestinal flora. Human intestinal bacteria were incubated with ginsenosides Rb1 , Rb2 , Rb3 and Rc at 37 °C under anaerobic conditions. Samples were taken at different timepoints. The transformed products were identified by rapid high-resolution liquid chromatography-quadrupole time-of-flight mass spectrometry. After 48 h of transformation, the transformed product of ginsenosides Rb1 , Rb2 , Rb3 and Rc was ginsenoside compound K. The transformation rates were 83.5 %, 88.7 %, 85.6 %, and 84.2 %. 16S rRNA sequencing technology was applied to the bioinformatic analysis of faecal samples incubated for 48 h. Relative to the blank control, the relative abundance of Firmicutes and Proteobacteria significantly increased at the phylum level. Moreover, the relative abundance of Bacteroidetes significantly decreased in ginsenosides Rb1 , Rb2 , Rb3 and Rc. At the genus level, the relative abundance of Escherichia significantly increased, whereas that of Dorea, Prevotella and Megasphaera significantly decreased in all groups. These results showed that Rb1 , Rb2 , Rb3 and Rc could improve the structure and diversity of human intestinal flora and balance the metabolic process.

Procoagulant and Antimicrobial Effects of Chitosan in Wound Healing.

Chitosan, a polysaccharide derived from chitin, has excellent wound healing properties, including intrinsic antimicrobial and hemostatic activities. This study investigated the effectiveness of chitosan dressing and compared it with that of regular gauze dressing in controlling clinically surgical bleeding wounds and profiled the community structure of the microbiota affected by these treatments. The dressings were evaluated based on biocompatibility, blood coagulation factors in rat, as well as antimicrobial and procoagulant activities, and the microbial phylogenetic profile in patients with abdominal surgical wounds. The chitosan dressing exhibited a uniformly fibrous morphology with a large surface area and good biocompatibility. Compared to regular gauze dressing, the chitosan dressing accelerated platelet aggregation, indicated by the lower ratio of prothrombin time and activated partial thromboplastin time, and had outstanding blood absorption ability. Adenosine triphosphate assay results revealed that the chitosan dressing inhibited bacterial growth up to 8 d post-surgery. Moreover, 16S rRNA-based sequencing revealed that the chitosan dressing effectively protected the wound from microbial infection and promoted the growth of probiotic microbes, thereby improving skin immunity and promoting wound healing. Our findings suggest that chitosan dressing is an effective antimicrobial and procoagulant and promotes wound repair by providing a suitable environment for beneficial microbiota.

Fatal cervix rupture due to intraplacental choriocarcinoma triggered by sexual intercourse.

A 27-year-old woman, gravida 1 para 0, died 30 min after intercourse at the 16th week of gestation. The prenatal medical history indicated the placental implantation position at the cervix. The autopsy revealed massive hemoperitoneum and a tumor in the placenta and myometrium on the anterior right side of the cervix. A transmural perforation was found from the tumor to the serosal surface of the cervix. The autopsy, histopathology, and medical history indicated that her death was ascribed to the rupture of the cervix due to intraplacental choriocarcinoma (IC) after intercourse. The case indicated that placental implantation and tumor invasion might lead to the rupture of the uterus triggered by external forces in daily life. This case study might increase the awareness and recognition of IC.

In Vitro Effects of Ginseng and the Seed of Zizyphus jujuba var. spinosa on Gut Microbiota of Rats with Spleen Deficiency.

Ginseng and the seed of Zizyphus jujuba var. spinosa, which are traditional Chinese medicinal materials, were often used in ancient Chinese recipes as a pair of medicines. They can replenish the primordial qi and tonify the spleen. This study investigated the effects of ginseng and the seed of Zizyphus jujuba var. spinosa (GS) extract on gut microbiota diversity in rats with spleen deficiency syndrome (SDS). A total of 52 compounds (including 16 flavonoids, 35 saponins, and 1 alkaloid) were identified and analyzed from the GS extract by UPLC-Q-Orbitrap-MS/MS. The GS extract significantly increased the relative abundance of Firmicutes and Bacteroidetes in rats with SDS but decreased that of Proteobacteria and Actinobacteria. At the genus level, the GS extract significantly increased the relative abundance of Lactobacillus and Bifidobacterium in rats with SDS but decreased that of Streptococcus, Escherichia-Shigella, Veillonella, and Enterococcus. In addition, the GS extract influenced glucose and amino acid metabolism. In summary, the results showed that the GS extract changed the structure and diversity of gut microbiota in rats with SDS and balanced the metabolic process.

Polymeric Gelatin Scaffolds Affect Mesenchymal Stem Cell Differentiation and Its Diverse Applications in Tissue Engineering.

Studies using polymeric scaffolds for various biomedical applications, such as tissue engineering, implants and medical substitutes, and drug delivery systems, have attempted to identify suitable material for tissue regeneration. This study aimed to investigate the biocompatibility and effectiveness of a gelatin scaffold seeded with human adipose stem cells (hASCs), including physical characteristics, multilineage differentiation in vitro, and osteogenic potential, in a rat model of a calvarial bone defect and to optimize its design. This functionalized scaffold comprised gelatin-hASCs layers to improve their efficacy in various biomedical applications. The gelatin scaffold exhibited excellent biocompatibility in vitro after two weeks of implantation. Furthermore, the gelatin scaffold supported and specifically regulated the proliferation and osteogenic and chondrogenic differentiation of hASCs, respectively. After 12 weeks of implantation, upon treatment with the gelatin-hASCs scaffold, the calvarial bone harboring the critical defect regenerated better and displayed greater osteogenic potential without any damage to the surrounding tissues compared to the untreated bone defect. These findings suggest that the present gelatin scaffold is a good potential carrier for stem cells in various tissue engineering applications.

[Therapeutic effect of Compound Qinlan Oral Liquid on treating combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome].

The aim of this paper was to investigate the therapeutic effect of Compound Qinlan Oral Liquid recommended by Provincial Novel Coronary Virus Pneumonia Treatment Scheme on the treatment of BALB/c mice with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome and to explore its clinical application in the treatment of novel coronavirus pneumonia, and to provide laboratory data support for clinical Chinese medicine. According to the classification of syndromes of novel coronavirus pneumonia by the national competent department of traditional Chinese medicine, this study determined that human coronavirus 229 E(HCoV-229 E)-infected mouse model of cold and dampness syndrome can be used to study human coronavirus pneumonia combined with pestilence attacking the lung syndrome model. This model is suitable for simulating traditional Chinese medicine treatment of common disease syndromes in Novel Coronavirus Pneumonia Diagnosis and Treatment program(trial implementation of the sixth edition). Specific steps are as follows. BALB/c mice of cold and dampness syndrome is infected with HCoV-229 E virus, and were divided into normal control group, infection control group, cold-dampness control group, cold-dampness infection group(the model group), and Compound Qilan Oral Liquid high dose group(22 mL·kg~(-1)·d~(-1)) and low dose group(11 mL·kg~(-1)·d~(-1)). On the day of infection, the Compound Qilan Oral Liquid was administered for three consecutive days. On the last dosing day, the lung tissue was dissected, and the lung index and inhibition rate were calculated. The nucleic acid of lung tissue was extracted and the HCoV-229 E virus load was detected by RT-PCR. Blood leukocytes were separated and the percentage of T and B lymphocytes was detected by flow cytometry. Lung tissue protein was extracted and the contents of IL-6, IL-10, TNF-α and IFN-γ were detected by ELISA. Serum was separated and the contents of gastrin(GAS) and motilin(MTL) were detected by ELISA. Histopathological analysis was performed with lung tissue. The high and low doses of Compound Qinlan Oral Liquid significantly reduced the lung index(P<0.01) of mice with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome, and the inhibition rates were 59.01% and 47.72%, respectively. Compared with the model control group, the high and low doses of Compound Qinlan Oral Liquid significantly reduced lung tissue viral load(P<0.01), increased cross blood CD4~+ T lymphocytes, CD8~+ T lymphocytes and total B lymphocyte percentage(P<0.01), reduced serum motilin content(P<0.01), reduced IL-6, IL-10, TNF-α and IFN-γ levels in lungs(P<0.01) and reduced lung tissue inflammation. Compound Qinlan Oral Liquid has a better effect on the mouse model with combining disease with syndrome of human coronavirus pneumonia with pestilence attacking lung syndrome, which may attribute to its function of in virus replication inhibition, gastrointestinal function improvement, immunity enhancement, and inflammatory factor reduction.

MW-PPG Sensor: An on-Chip Spectrometer Approach.

Multi-wavelength photoplethysmography (MW-PPG) sensing technology has been known to be superior to signal-wavelength photoplethysmography (SW-PPG) sensing technology. However, limited by the availability of sensing detectors, many prior studies can only use conventional bulky and pricy spectrometers as the detectors, and hence cannot bring the MW-PPG technology to daily-life applications. In this study we developed a chip-scale MW-PPG sensor using innovative on-chip spectrometers, aimed at wearable applications. Also in this paper we present signal processing methods for robustly extracting the PPG signals, in which an increase of up to 50% in the signal-to-noise ratio (S/N) was observed. Example measurements of saturation of peripheral blood oxygen (SpO2) and blood pressure were conducted.

[Intelligent and lean manufacturing for Chinese medicine:theory and its applications].

To cope with the " six major scientific problems" and the " five major technical challenges" of intelligent manufacturing and lean production of Chinese medicine( CM),we systematically proposed strategies,methods and the engineering theory of intelligent and lean manufacturing for CM by integrating the holistic view of traditional Chinese medicine and the concepts inspired from international advanced pharmaceutical technology. Moreover,the translational research of the theory and methods was successfully applied to six CMs such as Xuesaitong Injection. Several intelligent production lines were designed and built on the basis of the theory and methods,which greatly accelerated the digitalization,networking,and intelligence manufacture for CM. As a conclusion,the theory and applications provide technical demonstration for technical upgrading and high-quality development of CM industry.

Correction to: Osteogenic prospective of deriving human dental stem cells in collagen matrix boost.

The original version of this article unfortunately contained a mistake. The country was incorrect in the authors affiliations. It should read as "ROC". The corrected affiliations are given below.