Apoptosis and NETotic cell death affect diabetic nephropathy independently: An study integrative study encompassing bioinformatics, machine learning, and experimental validation.

OBJECTIVE: Although programmed cell death (PCD) and diabetic nephropathy (DN) are intrinsically conneted, the interplay among various PCD forms remains elusive. In this study, We aimed at identifying independently DN-associated PCD pathways and biomarkers relevant to the related pathogenesis. METHODS: We acquired DN-related datasets from the GEO database and identified PCDs independently correlated with DN (DN-PCDs) through single-sample Gene Set Enrichment Analysis (ssGSEA) as well as, univariate and multivariate logistic regression analyses. Subsequently, applying differential expression analysis, weighted gene co-expression network analysis (WGCNA), and Mfuzz cluster analysis, we filtered the DN-PCDs pertinent to DN onset and progression. The convergence of various machine learning techniques ultimately spotlighted hub genes, substantiated through dataset meta-analyses and experimental validations, thereby confirming hub genes and related pathways expression consistencies. RESULTS: We harmonized four DN-related datasets (GSE1009, GSE142025, GSE30528, and GSE30529) post-batch-effect removal for subsequent analyses. Our differential expression analysis yielded 709 differentially expressed genes (DEGs), comprising 446 upregulated and 263 downregulated DEGs. Based on our ssGSEA as well as univariate and multivariate logistic regressions, apoptosis and NETotic cell death were appraised as independent risk factors for DN (Odds Ratio > 1, p < 0.05). Next, we further refined 588 apoptosis- and NETotic cell death-associated genes through WGCNA and Mfuzz analysis, resulting in the identification of 17 DN-PCDs. Integrating protein-protein interaction (PPI) network analyses, network topology, and machine learning, we pinpointed hub genes (e.g., IL33, RPL11, and CX3CR1) as significant DN risk factors with expression corroborating in subsequent meta-analyses and experimental validations. Our GSEA enrichment analysis discerned differential enrichments between DN and control samples within pathways such as IL2/STAT5, IL6/JAK/STAT3, TNF-α via NF-κB, apoptosis, and oxidative phosphorylation, with related proteins such as IL2, IL6, and TNFα, which we subsequently submitted to experimental verification. CONCLUSION: Innovatively stemming from from PCD interactions, in this study, we discerned PCDs with an independent impact on DN: apoptosis and NETotic cell death. We further screened DN evolution- and progression-related biomarkers, i.e. IL33, RPL11, and CX3CR1, all of which we empirically validated. This study not only poroposes a PCD-centric perspective for DN studies but also provides evidence for PCD-mediated immune cell infiltration exploration in DN regulation. Our results could motivate further exploration of DN pathogenesis, such as how the inflammatory microenvironment mediates NETotic cell death in DN regulation, representing a promising direction for future research.

Digital Alloy-Grown InAs/GaAs Short-Period Superlattices with Tunable Band Gaps for Short-Wavelength Infrared Photodetection.

The InGaAs lattice-matched to InP has been widely deployed as the absorption material in short-wavelength infrared photodetection applications such as imaging and optical communications. Here, a series of digital alloy (DA)-grown InAs/GaAs short-period superlattices were investigated to extend the absorption spectral range. The scanning transmission electron microscopy, high-resolution X-ray diffraction, and atomic force microscopy measurements exhibit good material quality, while the photoluminescence (PL) spectra demonstrate a wide band gap tunability for the InGaAs obtained via the DA growth technique. The photoluminescence peak can be effectively shifted from 1690 nm (0.734 eV) for conventional random alloy (RA) InGaAs to 1950 nm (0.636 eV) for 8 monolayer (ML) DA InGaAs at room temperature. The complete set of optical constants of DA InGaAs has been extracted via the ellipsometry technique, showing the absorption coefficients of 398, 831, and 1230 cm-1 at 2 µm for 6, 8, and 10 ML DA InGaAs, respectively. As the period thickness increases for DA InGaAs, a red shift at the absorption edge can be observed. Furthermore, the simulated band structures of DA InGaAs via an environment-dependent tight binding model agree well with the measured photoluminescence peaks, which is advantageous for a physical understanding of band structure engineering via the DA growth technique. These investigations and results pave the way for the future utilization of the DA-grown InAs/GaAs short-period superlattices as a promising absorption material choice to extend the photodetector response beyond the cutoff wavelength of random alloy InGaAs.

Exposure to wildfires and health outcomes of vulnerable people: Evidence from US data.

This paper investigates the causal effect of wildfire exposure on birth outcomes and older people's health outcomes in United States (US). The study focuses on three sub-questions for each health outcome: (1) the causal effect of each of the five largest wildfires on individual health, (2) the causal impact of multiple large wildfires on individual health outcomes, and (3) the causal influence of wildfires larger than different sizes within different distances of counties on health outcomes at the county level. The analysis exploits data from National Vital Statistics System, Behavioural Risk Factor Surveillance System and FIRESTAT. In terms of birth outcomes, the findings show that the largest wildfire slightly increased the risk of other circulatory or respiratory anomalies. Multiple large wildfires moderately raised the risk of prematurity and led to a small decline in the probability of getting omphalocele and cleft lip. The county-level analysis suggests an increased risk of macrosomia following maternal exposure to wildfires. As for the elderly aged 65 + , the results indicate that exposure to multiple massive wildfires led to frequent occurrence of asthma symptoms, while the largest wildfire led to sleeping difficulty caused by asthma symptoms. The number of days older people experienced psychological problems was increased following exposure to multiple large wildfires.

Characterization of cuproptosis in gastric cancer and relationship with clinical and drug reactions.

Gastric cancer (GC) is the fifth most common cancer worldwide. Cuproptosis is associated with cell growth and death as well as tumorigenesis. Aiming to lucubrate the potential influence of CRGs in gastric cancer, we acquired datasets of gastric cancer patients from TCGA and GEO. The identification of molecular subtypes with CRGs expression was achieved through unsupervised learning-cluster analysis. To evaluate the application value of subtypes, the K-M survival analysis was conducted to evaluate the clinical prognostic characteristics. Subsequently, we performed Gene Set Variation Analysis (GSVA) and utilized ssGSEA to quantify the extent of immune infiltration. Further, the K-M survival analysis was used to identify the prognosis-related CRGs. Next, signature genes of diagnostic predictive value were screened using the least absolute shrinkage and selection operator (LASSO) algorithm from the expression matrix for TCGA, as well as the signature gene-related subtype was clustered by the "ConsensusClusterPlus" package. Finally, the immunological and drug sensitivity assessments of the signature gene-related subtypes were conducted. A total of 173 CRGs were identified, most of the CRGs undergo copy number variation in gastric cancer. Under different patient subtypes, immune cell levels differed significantly, and the subtype exhibiting high expression of the CRGs had a better prognosis. Furthermore, we selected 34 CRGs that were highly correlated with the prognosis of gastric cancer. By constructing a multivariate Cox proportional-hazards model and a hazard scoring system, we were able to categorize patients into high- and low-risk groups based on their hazard score. K-M analysis demonstrated a significant survival disadvantage in the high-risk group. Based on Lasso regression analysis, we screened 16 signature genes, a multivariate logistic regression model [cutoff: 0.149 (0.000, 0.974), AUC:0.987] and a prognosis network diagram was constructed and their prediction efficiency for gastric cancer prognostic diagnosis was well validated. According to the signature genes, the patients were separated to two signature subtypes. We found that patients with higher CRGs expression and better prognosis had lower levels of immune infiltration. Finally, according to the results of drug susceptibility analysis, docetaxel, 5-Fluorouracil, gemcitabin, and paclitaxel were found to be more sensitive to gastric cancer.

Endothelial Brg1 fine-tunes Notch signaling during zebrafish heart regeneration.

Myocardial Brg1 is essential for heart regeneration in zebrafish, but it remains unknown whether and how endothelial Brg1 plays a role in heart regeneration. Here, we found that both brg1 mRNA and protein were induced in cardiac endothelial cells after ventricular resection and endothelium-specific overexpression of dominant-negative Xenopus Brg1 (dn-xbrg1) inhibited myocardial proliferation and heart regeneration and increased cardiac fibrosis. RNA-seq and ChIP-seq analysis revealed that endothelium-specific overexpression of dn-xbrg1 changed the levels of H3K4me3 modifications in the promoter regions of the zebrafish genome and induced abnormal activation of Notch family genes upon injury. Mechanistically, Brg1 interacted with lysine demethylase 7aa (Kdm7aa) to fine-tune the level of H3K4me3 within the promoter regions of Notch family genes and thus regulated notch gene transcription. Together, this work demonstrates that the Brg1-Kdm7aa-Notch axis in cardiac endothelial cells, including the endocardium, regulates myocardial proliferation and regeneration via modulating the H3K4me3 of the notch promoters in zebrafish.

Dynamic-quenching of a single-photon avalanche photodetector using an adaptive resistive switch.

One of the most common approaches for quenching single-photon avalanche diodes is to use a passive resistor in series with it. A drawback of this approach has been the limited recovery speed of the single-photon avalanche diodes. High resistance is needed to quench the avalanche, leading to slower recharging of the single-photon avalanche diodes depletion capacitor. We address this issue by replacing a fixed quenching resistor with a bias-dependent adaptive resistive switch. Reversible generation of metallic conduction enables switching between low and high resistance states under unipolar bias. As an example, using a Pt/Al2O3/Ag resistor with a commercial silicon single-photon avalanche diodes, we demonstrate avalanche pulse widths as small as ~30 ns, 10× smaller than a passively quenched approach, thus significantly improving the single-photon avalanche diodes frequency response. The experimental results are consistent with a model where the adaptive resistor dynamically changes its resistance during discharging and recharging the single-photon avalanche diodes.

GPC2 Is a Potential Diagnostic, Immunological, and Prognostic Biomarker in Pan-Cancer.

Background: Glypican 2 (GPC2), a member of glypican (GPC) family genes, produces proteoglycan with a glycosylphosphatidylinositol anchor. It has shown its ascending significance in multiple cancers such as neuroblastoma, malignant brain tumor, and small-cell lung cancer. However, no systematic pan-cancer analysis has been conducted to explore its function in diagnosis, prognosis, and immunological prediction. Methods: By comprehensive use of datasets from The Cancer Genome Atlas (TCGA), Cancer Cell Line Encyclopedia (CCLE), Genotype-Tissue Expression Project (GTEx), cBioPortal, Human Protein Atlas (HPA), UALCAN, StarBase, and Comparative Toxicogenomics Database (CTD), we adopted bioinformatics methods to excavate the potential carcinogenesis of GPC2, including dissecting the correlation between GPC2 and prognosis, gene mutation, immune cell infiltration, and DNA methylation of different tumors, and constructed the competing endogenous RNA (ceRNA) networks of GPC2 as well as explored the interaction of GPC2 with chemicals and genes. Results: The results indicated that GPC2 was highly expressed in most cancers, except in pancreatic adenocarcinoma, which presented at a quite low level. Furthermore, GPC2 showed the early diagnostic value in 16 kinds of tumors and was positively or negatively associated with the prognosis of different tumors. It also verified that GPC2 was a gene associated with most immune-infiltrating cells in pan-cancer, especially in thymoma. Moreover, the correlation with GPC2 expression varied depending on the type of immune-related genes. Additionally, GPC2 gene expression has a correlation with DNA methylation in 20 types of cancers. Conclusion: Through pan-cancer analysis, we discovered and verified that GPC2 might be useful in cancer detection for the first time. The expression level of GPC2 in a variety of tumors is significantly different from that of normal tissues. In addition, the performance of GPC2 in tumorigenesis and tumor immunity also confirms our conjecture. At the same time, it has high specificity and sensitivity in the detection of cancers. Therefore, GPC2 can be used as an auxiliary indicator for early tumor diagnosis and a prognostic marker for many types of tumors.

Linggui Zhugan Decoction for peripheral vertigo: A protocol for systematic review and meta-analysis.

BACKGROUND: Vertigo is a sense of movement or rotation of the patient's own or an external object. At present, western medicine treatment such as vestibular suppressant medications commonly used in clinical practice are ineffective and have adverse reactions. In traditional Chinese medicine, Linggui Zhugan Decoction (LZD) was used by doctors to warm yang for resolving fluid retention, strengthen the spleen and clear away dampness, with significant effect. Recently, some clinical studies have also shown that LZD has reliable effect in treating peripheral vertigo, but there is no systematic evidence. Therefore, this study aims to objectively evaluate the efficacy and safety of LZD in the treatment of peripheral vertigo. METHODS: Eight electronic databases will be searched from inception to August 2020 by 2 independent researchers, in order to collect qualified randomized controlled trials (RCTs) on the LZD treatment for peripheral vertigo. The therapeutic effects according to Clinical efficacy will be adopted as the primary outcomes. RevMan V.5.3 software will be used for the data synthesis and the Cochrane's risk of bias assessment tool will be used to assess the risk of bias. RESULTS: This review will conduct a high-quality synthesis on present evidence of LZD for peripheral vertigo. CONCLUSION: The conclusion of the study will indicate whether LZD is an effective treatment for peripheral vertigo by providing updated evidence. PROSPERO REGISTRATION NUMBER: PROSPERO CRD 42021238817.

Light-sheet fluorescence imaging charts the gastrula origin of vascular endothelial cells in early zebrafish embryos.

It remains challenging to construct a complete cell lineage map of the origin of vascular endothelial cells in any vertebrate embryo. Here, we report the application of in toto light-sheet fluorescence imaging of embryos to trace the origin of vascular endothelial cells (ECs) at single-cell resolution in zebrafish. We first adapted a previously reported method to embryo mounting and light-sheet imaging, created an alignment, fusion, and extraction all-in-one software (AFEIO) for processing big data, and performed quantitative analysis of cell lineage relationships using commercially available Imaris software. Our data revealed that vascular ECs originated from broad regions of the gastrula along the dorsal-ventral and anterior-posterior axes, of which the dorsal-anterior cells contributed to cerebral ECs, the dorsal-lateral cells to anterior trunk ECs, and the ventral-lateral cells to posterior trunk and tail ECs. Therefore, this work, to our knowledge, charts the first comprehensive map of the gastrula origin of vascular ECs in zebrafish, and has potential applications for studying the origin of any embryonic organs in zebrafish and other model organisms.

Photoelectrochemistry of Self-Limiting Electrodeposition of Ni Film onto GaAs.

Gallium arsenide (GaAs) provides a suitable bandgap (1.43 eV) for solar spectrum absorption and allows a larger photovoltage compared to silicon, suggesting great potential as a photoanode toward water splitting. Photocorrosion under water oxidation condition, however, leads to decomposition or the formation of an insulating oxide layer, which limits the photoelectrochemical performance and stability of GaAs. In this work, a self-limiting electrodeposition method of Ni on GaAs is reported to either generate ultra-thin continuous film or nanoislands with high particle density by controlling deposition time. The self-limiting growth mechanism is validated by potential transients, X-ray photoelectron spectroscopy composition and depth profile measurements. This deposition method exhibits a rapid nucleation, forms an initial metallic layer followed by a hydroxide/oxyhydroxide nanofilm on the GaAs surface and is independent of layer thickness versus deposition time when coalescence is reached. A photocurrent up to 8.9 mA cm-2 with a photovoltage of 0.11 V is obtained for continuous ultrathin films, while a photocurrent density of 9.2 mA cm-2 with a photovoltage of 0.50 V is reached for the discontinuous nanoislands layers in an aqueous solution containing the reversible redox couple K3 Fe(CN)6 /K4 Fe(CN)6 .

Triple-mesa avalanche photodiodes with very low surface dark current.

The dark current of a photodetector is a key parameter for high-sensitivity optical receivers. We report low-dark-current, triple-mesa avalanche photodiodes that have ~50 times lower dark current than conventional single-mesa devices, and suppress surface leakage. The tolerances of triple-mesa avalanche photodiode parameters are presented.

III-V on silicon avalanche photodiodes by heteroepitaxy.

We demonstrate a III-V avalanche photodiode (APD) grown by heteroepitaxy on silicon. This InGaAs/InAlAs APD exhibits low dark current, gain >20, external quantum efficiency >40%, and similar low excess noise, k∼0.2, as InAlAs APDs on InP.

A novel inducible mutagenesis screen enables to isolate and clone both embryonic and adult zebrafish mutants.

Conventional genetic screens for recessive mutants are inadequate for studying biological processes in the adult vertebrate due to embryonic lethality. Here, we report that a novel inducible mutagenesis system enables to study gene function in both embryonic and adult zebrafish. This system yields genetic mutants with conditional ectopic over- or under-expression of genes in F1 heterozygotes by utilizing inducible Tet-On transcriptional activation of sense or anti-sense transcripts from entrapped genes by Tol2 transposase-meditated transgenesis. Pilot screens identified 37 phenotypic mutants displaying embryonic defects (34 lines), adult fin regeneration defects (7 lines), or defects at both stages (4 lines). Combination of various techniques (such as: generating a new mutant allele, injecting gene specific morpholino or mRNA etc) confirms that Dox-induced embryonic abnormalities in 10 mutants are due to dysfunction of entrapped genes; and that Dox-induced under-expression of 6 genes causes abnormal adult fin regeneration. Together, this work presents a powerful mutagenesis system for genetic analysis from zebrafish embryos to adults in particular and other model organisms in general.

Study on spin and optical polarization in a coupled InGaN/GaN quantum well and quantum dots structure.

The spin and optical polarization based on a coupled InGaN/GaN quantum well (QW) and quantum dots (QDs) structure is investigated. In this structure, spin-electrons can be temporarily stored in QW, and spin injection from the QW into QDs via spin-conserved tunneling is enabled. Spin relaxation can be suppressed owing to the small energy difference between the initial state in the QW and the final states in the QDs. Photoluminescence (PL) and time-resolved photoluminescence (TRPL) measurements are carried out on optical spin-injection and -detection. Owing to the coupled structure, spin-conserved tunneling mechanism plays a significant role in preventing spin relaxation process. As a result, a higher circular polarization degree (CPD) (~49.1%) is achieved compared with conventional single layer of QDs structure. Moreover, spin relaxation time is also extended to about 2.43 ns due to the weaker state-filling effect. This coupled structure is believed an appropriate candidate for realization of spin-polarized light source.

Low-temperature-dependent property in an avalanche photodiode based on GaN/AlN periodically-stacked structure.

In ultra-high sensitive APDs, a vibrate of temperature might bring a fatal decline of the multiplication performance. Conventional method to realize a temperature-stable APD focuses on the optimization of device structure, which has limited effects. While in this paper, a solution by reducing the carrier scattering rate based on an GaN/AlN periodically-stacked structure (PSS) APD is brought out to improve temperature stability essentially. Transport property is systematically investigated. Compared with conventional GaN homojunction (HJ) APDs, electron suffers much less phonon scatterings before it achieves ionization threshold energy and more electrons occupy high energy states in PSS APD. The temperature dependence of ionization coefficient and energy distribution is greatly reduced. As a result, temperature stability on gain is significantly improved when the ionization happens with high efficiency. The change of gain for GaN (10 nm)/AlN (10 nm) PSS APD from 300 K to 310 K is about 20% lower than that for HJ APD. Additionally, thicker period length is found favorable to ionization coefficient ratio but a bit harmful to temperature stability, while increasing the proportion of AlN at each period in a specific range is found favorable to both ionization coefficient ratio and temperature stability.

[Early treatment of large soft-tissue wounds with intermittent vacuum sealing drainage].

OBJECTIVE: To evaluate the early clinical efficacy of large soft-tissue wounds with intermittent vacuum sealing drainage. METHODS: From March 2009 to June 2010, the study group was comprised of 56 patients treated with intermittent vacuum sealing drainage. There were 47 males and 9 females with a mean age of 37.5 years (range: 16 - 65). Intermittent vacuum sealing drainage was immediately used after an emergency operation. The mean duration of treatment was 2.5 weeks (range: 1 - 4). The granulation status was observed and wound dressing changed weekly. RESULTS: Among them, all wound surfaces were dry and granulation tissues brightly red. There was no deep infection. The mean healing durations of intermittent and continuous vacuum sealing drainage groups were (32 ± 4.5) and (37 ± 7.5) days respectively. And there was no statistical difference (P > 0.05). CONCLUSION: Intermittent vacuum sealing drainage promotes a rapid and copious production of granulation tissue over soft tissue wound. The patient suffering is minimal and the dressings are easy to manage.

[Treatment of lumbar disc herniation by modified transforaminal lumbar interbody fusion with a pedicle screw system].

OBJECTIVE: To evaluate the outcomes of modified transforaminal lumbar interbody fusion in patients with lumbar disc herniation. METHODS: Forty-six cases of lumbar disc herniation were treated by modified transforaminal lumbar interbody fusion. There were 32 males and 14 females with a mean age of 47 years old (range: 27 - 65). The mean course of disease was 7.5 years (range: 4 - 18). Eighteen cases were of single-level lumbar disc herniation, including L3/4 (n = 5), L4/5 (n = 8) and L5/S1 (n = 5). There were 28 cases with lumbar degenerative diseases at other levels. Preoperatively, the score of visual analogue scale (VAS) was 8.9 ± 1.3 and the score of Oswestry disability index (ODI) was 57.3 ± 5.2. All patients received a normal conservative treatment for at least 3 months with no therapeutic effect at pre-operation. RESULTS: Forty-six cases had an average follow-up of 20 months (range: 12 - 20). The operative duration was an average of 160 minutes (range: 120 - 180). And the average volume of intra-operative blood loss was 550 ml (range: 400 - 800). There was no severe complication. The symptoms became stable after three months. At 3 months postoperatively, the score of VAS was 2.0 ± 0.4 and the score of ODI 15.2 ± 3.4. And there were significant differences between preoperative and postoperative values (P < 0.05). The improvement rates of postoperative VAS and ODI were (80.1 ± 4.7)% and (73.6 ± 2.8)% respectively. All patients achieved lumbar interbody bone fusion at 12 months post-operation with a fusion rate of 100%. For the therapeutic effect, 34 cases were regarded as excellent, 8 good and 4 fair with an excellent/good rate of 91.3%. All patients began to walk with orthosis after 3 days and resumed their jobs and normal lives after 3 months. CONCLUSION: Modified transforaminal lumbar interbody fusion is effective for the treatment of lumbar disc herniation. Making a detailed operative plan on the basis of preoperative images and symptoms is essential.

[Surgical treatment of open fractures of the talus].

OBJECTIVE: To evaluate the long-term outcomes of surgical treatment of open fracture of talus. METHODS: Sixteen patients with displaced open fractures of the talus, including 3 cases of type 1, 8 of type 2, 2 of type 3A, 2 of type 3B, and 1 of type 3C according to the Gustilo-Anderson classification system, 15 males and 1 female, aged 37.5 (21 - 48), were treated with open reduction and stable internal fixation within 6 - 8 hours after injury, and followed up for 3.2 years (3 - 6 years). There were 7 cases of pure displaced talar neck or body fracture and 9 cases of fractures associated with an ipsilateral pilon, ankle, and calcaneus totally that included 2 cases of type 2, 3 of type 3, and 1 of type 4 according to the Hawkins classification system modified by Canale. RESULTS: The union rate was 81% (13/16) with the average union time of 4.5 months. Three cases failed to heal and developed osteomyelitis, of which 2 were treated with late talectomy because of septic nonunion. One case underwent amputation below-the-knee because of instability and pain. Osteonecrosis developed after seven of the nineteen closed fractures, whereas posttraumatic arthritis developed after all nineteen. Osteonecrosis developed in 11 (68%), and posttraumatic arthritis developed in 13 of the 16 cases (85%). The average American Orthopaedic Foot and Ankle Society score of these patients was 43.7 points. CONCLUSION: Open fractures of the talus has a low union rate, a higher osteonecrosis rate, and substantially higher reoperation and infection rates. Posttraumatic arthritis is a more common complication than osteonecrosis following operative treatment. Open reduction and internal fixation are recommended for the treatment of open fractures of talus.