Knockdown of KBTBD7 attenuates septic lung injury by inhibiting ferroptosis and improving mitochondrial dysfunction.

Lung injury in sepsis is caused by an excessive inflammatory response caused by the entry of pathogenic microorganisms into the body. It is also accompanied by the production of large amounts of ROS. Ferroptosis and mitochondrial dysfunction have also been shown to be related to sepsis. Finding suitable sepsis therapeutic targets is crucial for sepsis research. BTB domain-containing protein 7 (KBTBD7) is involved in regulating inflammatory responses, but its role and mechanism in the treatment of septic lung injury are still unclear. In this study, we evaluated the role and related mechanisms of KBTBD7 in septic lung injury. In in vitro studies, we established an in vitro model by inducing human alveolar epithelial cells with lipopolysaccharide (LPS) and found that KBTBD7 was highly expressed in the in vitro model. KBTBD7 knockdown could reduce the inflammatory response by inhibiting the secretion of pro-inflammatory factors and inhibit the production of ROS, ferroptosis and mitochondrial dysfunction. Mechanistic studies show that KBTBD7 interacts with FOXA1, promotes FOXA1 expression, and indirectly inhibits SLC7A11 transcription. In vivo studies have shown that knocking down KBTBD7 improves lung tissue damage in septic lung injury mice, inhibits inflammatory factors, ROS production and ferroptosis. Taken together, knockdown of KBTBD7 shows an alleviating effect on septic lung injury in vitro and in vivo, providing a potential therapeutic target for the treatment of septic lung injury.

E3 Ubiquitin Ligase NEDD4L Negatively Regulates Skin Tumorigenesis by Inhibiting IL-6/GP130 Signaling Pathway.

IL-6 signaling plays a crucial role in the survival and metastasis of skin cancer. NEDD4L acts as a suppressor of IL-6 signaling by targeting GP130 degradation. However, the effects of the NEDD4L-regulated IL-6/GP130 signaling pathway on skin cancer remain unclear. In this study, protein expression levels of NEDD4L and GP130 were measured in tumor tissues from patients with cutaneous squamous cell carcinoma. Skin tumors were induced in wild-type and Nedd4l-knockout mice, and activation of the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway was detected. The results indicated a negative correlation between the protein expression levels of NEDD4L and GP130 in cutaneous squamous cell carcinoma tissues from patients. Nedd4l deficiency significantly promoted 7,12-dimethylbenz[a]anthracene/12-O-tetradecanoylphorbol-13-acetate-induced skin tumorigenesis and benign-to-malignant conversion by activating the IL-6/GP130/signal transducer and activator of transcription 3 signaling pathway, which was abrogated by supplementation with the GP130 inhibitor SC144. Furthermore, our findings suggested that NEDD4L can interact with GP130 and promote its ubiquitination in skin tumors. In conclusion, our results indicate that NEDD4L could act as a tumor suppressor in skin cancer, and inhibition of GP130 could be a potential therapeutic method for treating this disease.

[Cadmium Phytoremediation Effect of Sweet Sorghum Assisted with Citric Acid on Typical Parent Soil in Southern China].

Sweet sorghum has a large biomass and strong cadmium (Cd) absorption capacity, which has the potential for phytoremediation of Cd-contaminated soil. In order to study the Cd phytoremediation effect of sweet sorghum assisted with citric acid on the typical parent materials in southern China, a field experiment was carried out in two typical parent material farmland areas (neutral purple mud field and jute sand mud field) with Cd pollution in Hunan Province. The results showed that:① Citric acid had no inhibitory effect on the growth of sweet sorghum. After the application of citric acid, the aboveground biomass of sweet sorghum at the maturity stage increased by 10.1%-24.7%. ② Both sweet sorghum planting and citric acid application reduced the soil pH value, and the application of citric acid further reduced the soil pH value at each growth stage of sweet sorghum; this decrease was greater in the neutral purple mud field, which decreased by 0.24-0.72 units. ③ Both sweet sorghum planting and citric acid application reduced the total amount of soil Cd, and the decreases in the neutral purple mud field and jute sand mud field were 23.8%-52.2% and 17.1%-31.8%, respectively. The acid-extractable percentage of soil Cd in both places increased by 38.6%-147.7% and 4.8%-22.7%, respectively. ④ The application of citric acid could significantly increase the Cd content in various tissues of sweet sorghum. The Cd content in the aboveground part of the plant in the neutral purple mud field was higher than that in the jute sand mud field, and the Cd content in stems and leaves was 0.25-1.90 mg·kg-1 and 0.21-0.64 mg·kg-1, respectively. ⑤ After applying citric acid, the Cd extraction amount of sweet sorghum in neutral purple mud soil in the mature stage reached 47.56 g·hm-2. In summary, citric acid could enhance the efficiency of sweet sorghum in the phytoremediation of Cd-contaminated soil, and the effect was better in neutral purple mud fields. This technology has the potential for remediation coupled with agro-production for heavy metal-contaminated farmland.

Deep Canonical Correlation Fusion Algorithm Based on Denoising Autoencoder for ASD Diagnosis and Pathogenic Brain Region Identification.

Autism Spectrum Disorder (ASD) is defined as a neurodevelopmental condition distinguished by unconventional neural activities. Early intervention is key to managing the progress of ASD, and current research primarily focuses on the use of structural magnetic resonance imaging (sMRI) or resting-state functional magnetic resonance imaging (rs-fMRI) for diagnosis. Moreover, the use of autoencoders for disease classification has not been sufficiently explored. In this study, we introduce a new framework based on autoencoder, the Deep Canonical Correlation Fusion algorithm based on Denoising Autoencoder (DCCF-DAE), which proves to be effective in handling high-dimensional data. This framework involves efficient feature extraction from different types of data with an advanced autoencoder, followed by the fusion of these features through the DCCF model. Then we utilize the fused features for disease classification. DCCF integrates functional and structural data to help accurately diagnose ASD and identify critical Regions of Interest (ROIs) in disease mechanisms. We compare the proposed framework with other methods by the Autism Brain Imaging Data Exchange (ABIDE) database and the results demonstrate its outstanding performance in ASD diagnosis. The superiority of DCCF-DAE highlights its potential as a crucial tool for early ASD diagnosis and monitoring.

Multi-kernel Learning Fusion Algorithm Based on RNN and GRU for ASD Diagnosis and Pathogenic Brain Region Extraction.

Autism spectrum disorder (ASD) is a complex, severe disorder related to brain development. It impairs patient language communication and social behaviors. In recent years, ASD researches have focused on a single-modal neuroimaging data, neglecting the complementarity between multi-modal data. This omission may lead to poor classification. Therefore, it is important to study multi-modal data of ASD for revealing its pathogenesis. Furthermore, recurrent neural network (RNN) and gated recurrent unit (GRU) are effective for sequence data processing. In this paper, we introduce a novel framework for a Multi-Kernel Learning Fusion algorithm based on RNN and GRU (MKLF-RAG). The framework utilizes RNN and GRU to provide feature selection for data of different modalities. Then these features are fused by MKLF algorithm to detect the pathological mechanisms of ASD and extract the most relevant the Regions of Interest (ROIs) for the disease. The MKLF-RAG proposed in this paper has been tested in a variety of experiments with the Autism Brain Imaging Data Exchange (ABIDE) database. Experimental findings indicate that our framework notably enhances the classification accuracy for ASD. Compared with other methods, MKLF-RAG demonstrates superior efficacy across multiple evaluation metrics and could provide valuable insights into the early diagnosis of ASD.

SARS-CoV-2 Neutralization Capacity in Hemodialysis Patients with and without a Fifth Vaccination with the Updated Comirnaty Original/Omicron BA.4-5 Vaccine.

BACKGROUND: Hemodialysis patients have reduced serologic immunity after SARS-CoV-2 vaccination compared to the general population and an increased risk of morbidity and mortality when exposed to SARS-CoV-2. METHODS: Sixty-six hemodialysis patients immunized four times with the original SARS-CoV-2 vaccines (BNT162b2, mRNA-1273) either received a booster with the adapted Comirnaty Original/Omicron BA.4-5 vaccine 8.3 months after the fourth vaccination and/or experienced a breakthrough infection. Two months before and four weeks after the fifth vaccination, the live-virus neutralization capacities of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were determined, as well as neutralizing and quantitative anti-SARS-CoV-2 spike-specific IgG antibodies. RESULTS: Four weeks after the fifth vaccination with the adapted vaccine, significantly increased neutralizing antibodies and the neutralization of Omicron variants BA.5, BQ.1.1, and XBB.1.5 were observed. The increase was significantly higher than after the fourth vaccination for variants BQ.1.1 and BA.5. Of all analyzed variants, BA.5 was neutralized best after the fifth vaccination. We did not see a difference in humoral immunity between the group with an infection and the group with a vaccination as a fifth spike exposure. Fivefold-vaccinated patients with a breakthrough infection showed a significantly higher neutralization capacity of XBB.1.5. CONCLUSION: A fifth SARS-CoV-2 vaccination with the adapted vaccine improves both wild-type specific antibody titers and the neutralizing capacity of the current Omicron variants BA.5, BQ.1.1, and XBB.1.5 in hemodialysis patients. Additional booster vaccinations with adapted vaccines will likely improve immunity towards current and original SARS-CoV-2 variants and are, therefore, recommended in hemodialysis patients. Further longitudinal studies must show the extent to which this booster vaccination avoids a breakthrough infection.

[Effect of Silica Fertilizer(Husk Ash) to Improve Soil Quality and Reduce Cd and As Accumulation in Rice].

A rice pot experiment was conducted to identify the effect of silica fertilizer prepared from husk ash on the soil bioavailability of cadmium (Cd) and arsenic (As), enzyme activities, microbial community structure, and heavy metal content in brown rice at different growth stages. The results showed that the application of 0.1%-1.0% silica fertilizer-husk ash increased the pH value of soil by 0.04-0.24 units and the content of soil available silicon by 44.2%-97.5%. It also decreased the content of available Cd and available As by 16.2%-21.4% and 16.0%-24.9%, respectively. With the increase in application amount, the soil enzyme activities increased at all growth stages, and the sucrase activity and the dehydrogenase activity significantly increased by 6.3%-145.7% and 6.7%-224.1%, respectively. The analysis of the soil microbial community composition structure at mature stages showed that the application of silica fertilizer-husk ash had no effect on microbial α-diversity, but it had a significant effect on microbial ß-diversity and then promoted microbial growth and maintained the stability of the community structure. With the increase in application amount, the contents of Cd in brown rice decreased by 29.3%-89.7%, and the contents of total As and inorganic As in brown rice decreased by 7.8%-42.3% and 17.2%-44.5%, respectively. Under the application of 0.5% and 1.0% silica fertilizer-husk ash, the Cd contents in brown rice were lower than 0.2 mg·kg-1, and the inorganic As contents in brown rice were lower than 0.35 mg·kg-1. In conclusion, the silica fertilizer-husk ash can improve soil quality and reduce the contents of Cd and As in brown rice, and it is eco-friendly and can be used to remedy the paddy soil contaminated with Cd and As.

[Effects of the Application of Irrigation Water Containing Zn at the Key Growth Period on the Uptake and Transport of Cd in Rice].

In this study， a field experiment was conducted to examine the effects of the application of irrigation water containing Zn at the key growth period （booting stage and filling stage） on exchangeable Cd content in the soil， Cd concentration in pore water， and Cd uptake and transport in rice in a Cd-contaminated paddy field in Liuyang City， Hunan Province. The results indicated that： ① the application of irrigation water containing Zn during the key growth period could inhibit the releasing process of exchangeable Cd from the soil into pore water. Compared with that in the control， the content of exchangeable Cd in soil was slightly changed， but the concentration of Cd in soil pore water at the mature stage was significantly reduced by 16.7%-57.6%. ② The application of irrigation water containing Zn at the key growth period could significantly reduce the Cd content in various parts of rice. Cd contents in root， stem， and brown rice with the application of irrigation water containing 20 mg·L-1 Zn before the booting and the filling stage （BF1） were significantly decreased by 56.0%， 83.8%， and 85.2%， respectively. ③ Compared with the application of 100 mg·L-1 irrigation water containing Zn， the application of 20 mg·L-1 irrigation water containing Zn significantly reduced the uptake and transport of Cd in rice， and the translocation factor （TF） of Cd from rice roots to stems was also significantly reduced by 12.5%-56.3%， with the B1 and BF1 treatments reaching significant levels. These results suggested that the application of irrigation water containing Zn could significantly reduce the uptake and accumulation of Cd in rice， and the application of 20 mg·L-1 irrigation water containing Zn before the booting and filling stage could effectively realize the safe production of Cd-contaminated paddy fields.

Diagnostic, prognostic, and therapeutic potential of exosomal microRNAs in renal cancer.

Renal cell carcinoma (RCC) arises from the tubular epithelial cells of the nephron. It has the highest mortality rate among urological cancers. There are no effective therapeutic approaches and no non-invasive biomarkers for diagnosis and follow-up. Thus, suitable novel biomarkers and therapeutic targets are essential for improving RCC diagnosis/prognosis and treatment. Circulating exosomes such as exosomal microRNAs (Exo-miRs) provide non-invasive prognostic/diagnostic biomarkers and valuable therapeutic targets, as they can be easily isolated and quantified and show high sensitivity and specificity. Exosomes secreted by an RCC can exhibit alterations in the miRs' profile that may reflect the cellular origin and (patho)physiological state, as a ''signature'' or ''fingerprint'' of the donor cell. It has been shown that the transportation of renal-specific miRs in exosomes can be rapidly detected and measured, holding great potential as biomarkers in RCC. The present review highlights the studies reporting tumor microenvironment-derived Exo-miRs with therapeutic potential as well as circulating Exo-miRs as potential diagnostic/prognostic biomarkers in patients with RCC.

Screening and evaluation of metabolites binding PRAS40 from Erxian decoction used to treat spinal cord injury.

Objective: The PRAS40 is an essential inhibitory subunit of the mTORC1 complex, which regulates autophagy. It has been suggested that Erxian Decoction (EXD) could treat spinal cord injury (SCI) via the autophagy pathway. However, the mechanism of whether EXD acts through PRAS40 remains unclear. Methods: With the help of immobilized PRAS40, isothermal titration calorimetry (ITC) and molecular docking, the bioactive metabolites in the EXD were screened. To establish in vitro SCI models, PC12 cells were exposed to hydrogen peroxide (H2O2) and then treated with the identified EXD substances. Furthermore, Western blot assay was carried out to identify potential molecular mechanisms involved. For assessing the effect of metabolites in vivo, the SCI model rats were first pretreated with or without the metabolite and then subjected to the immunohistochemistry (IHC) staining, Basso, Beattie & Bresnahan (BBB) locomotor rating scale, and H&E staining. Results: The immobilized PRAS40 isolated indole, 4-nitrophenol, terephthalic acid, palmatine, sinapinaldehyde, and 3-chloroaniline as the potential ligands binding to PRAS40. Furthermore, the association constants of palmatine and indole as 2.84 × 106 M-1 and 3.82 × 105 M-1 were elucidated via ITC due to the drug-like properties of these two metabolites. Molecular docking results also further demonstrated the mechanism of palmatine binding to PRAS40. Western blot analysis of PC12 cells demonstrated that palmatine inhibited the expression of p-mTOR by binding to PRAS40, activating the autophagic flux by markedly increasing LC3. The injection of palmatine (10µM and 20 µM) indicated notably increased BBB scores in the SCI rat model. Additionally, a dose-dependent increase in LC3 was observed by IHC staining. Conclusion: This research proved that EXD comprises PRAS40 antagonists, and the identified metabolite, palmatine, could potentially treat SCI by activating the autophagic flux.

Deep integrated fusion of local and global features for cervical cell classification.

Cervical cytology image classification is of great significance to the cervical cancer diagnosis and prognosis. Recently, convolutional neural network (CNN) and visual transformer have been adopted as two branches to learn the features for image classification by simply adding local and global features. However, such the simple addition may not be effective to integrate these features. In this study, we explore the synergy of local and global features for cytology images for classification tasks. Specifically, we design a Deep Integrated Feature Fusion (DIFF) block to synergize local and global features of cytology images from a CNN branch and a transformer branch. Our proposed method is evaluated on three cervical cell image datasets (SIPaKMeD, CRIC, Herlev) and another large blood cell dataset BCCD for several multi-class and binary classification tasks. Experimental results demonstrate the effectiveness of the proposed method in cervical cell classification, which could assist medical specialists to better diagnose cervical cancer.

Switching from Thermally Activated Delayed Fluorescence in Single Crystals for Low-Threshold Laser to Room-temperature Phosphorescence in Amorphous-Film for Highly Efficient OLEDs.

Metal-organic phosphorescent complexes containing Ir or Pt are work horse in organic light-emitting diode (OLED) technology, which can harvest both singlet and triplet excitons in electroluminescence (EL) owing to strong heavy-atom effect. Recently, organic room-temperature phosphorescence (ORTP) have achieved high photoluminescence quantum yield (PLQY) in rigid crystalline state, which, however, is unsuitable for OLED fabrication, therefore leading to an EL efficiency far low behind those of metal-organic phosphorescent complexes. Here, we reported a luminescence mechanism switch from thermally activated delayed fluorescence (TADF) in single crystal microwires to ORTP in amorphous thin-films, based on a tert-butylcarbazole difluoroboron ß-diketonate derivative of DtCzBF2. Tightly packed and well-faceted single-crystal microwires exhibit aggregation induced emission (AIE), enabling TADF microlasers at 473 nm with an optical gain coefficient as high as 852 cm-1 . In contrast, loosely packed dimers of DtCzBF2 formed in guest-host amorphous thin-films decrease the oscillator strength of fluorescence transition but stabilize triplets for ORTP with a PLQY up to 61 %, leading to solution-processed OLEDs with EQE approaching 20 %. This study opens possibilities of low-cost ORTP emitters for high performance OLEDs and future low-threshold electrically injected organic semiconductor lasers (OSLs).

Combined transcriptomics and proteomics studies on the effect of electrical stimulation on spinal cord injury in rats.

Electrical stimulation (ES) of the spinal cord is a promising therapy for functional rehabilitation after spinal cord injury (SCI). However, the specific mechanism of action is poorly understood. We designed and applied an implanted ES device in the SCI area in rats and determined the effect of ES on the treatment of motor dysfunction after SCI using behavioral scores. Additionally, we examined the molecular characteristics of the samples using proteomic and transcriptomic sequencing. The differential molecules between groups were identified using statistical analyses. Molecular, network, and pathway-based analyses were used to identify group-specific biological features. ES (0.5 mA, 0.1 ms, 50 Hz) had a positive effect on motor dysfunction and neuronal regeneration in rats after SCI. Six samples (three independent replicates in each group) were used for transcriptome sequencing; we obtained 1026 differential genes, comprising 274 upregulated genes and 752 downregulated genes. A total of 10 samples were obtained: four samples in the ES group and six samples in the SCI group; for the proteome sequencing, 48 differential proteins were identified, including 45 up-regulated and three down-regulated proteins. Combined transcriptomic and proteomic studies have shown that the main enrichment pathway is the hedgehog signaling pathway. Western blot results showed that the expression levels of Sonic hedgehog (SHH) (P < 0.001), Smoothened (SMO) (P = 0.0338), and GLI-1 (P < 0.01) proteins in the ES treatment group were significantly higher than those in the SCI group. The immunofluorescence results showed significantly increased expression of SHH (P = 0.0181), SMO (P = 0.021), and GLI-1 (P = 0.0126) in the ES group compared with that in the SCI group. In conclusion, ES after SCI had a positive effect on motor dysfunction and anti-inflammatory effects in rats. Moreover, transcriptomic and proteomic sequencing also provided unique perspectives on the complex relationships between ES on SCI, where the SHH signaling pathway plays a critical role. Our study provides a significant theoretical foundation for the clinical implementation of ES therapy in patients with SCI.

Comparative study on the technique and efficacy of microscope-assisted MI-TLIF and naked-eye MI-TLIF in lumbar revision surgery.

BACKGROUND: Lumbar revision surgery can be performed by simple lumbar nerve decompression or lumbar interbody fusion, including percutaneous endoscopic lumbar discectomy, transforaminal lumbar interbody fusion (TLIF), etc. However, lumbar revision surgery is very difficult in surgical operation. We sought to explore the technique safety and efficacy of microscope-assisted minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) in lumbar revision surgery. METHODS: Cases of postoperative recurrence following lumbar spine surgery (n = 63) treated from December 2016 to July 2021 were retrospectively analyzed, including 24 cases of microscope-assisted MI-TLIF (microscopic group) and 39 cases of naked-eye MI-TLIF (naked-eye group). The operation time, intraoperative blood loss, incision length, postoperative drainage, length of hospital stay, initial operation, and visual analog score (VAS) of low back and leg pain before and at 7 days and 3 months after the operation and the last follow-up were compared between the two groups. The Oswestry Dysfunction Index (ODI) and the Japanese Orthopaedic Association (JOA) scores before and after the operation and the Bridwell interbody fusion grades at 1 year were compared. The independent t tests, Mann-Whitney U tests, and Chi-square tests were used for analysis. RESULTS: All 63 patients were successfully treated by operation and were followed up for an average of 31.5 ± 8.6 months (range 12-48 months). The two groups had no significant difference in sex, age, incision length, initial operation, or operative segment (P > 0.05). There was no significance in operation time, VAS score, ODI score, and JOA score of low back pain or Bridwell interbody fusion grade between the two groups (P > 0.05). Significant differences in intraoperative blood loss, postoperative drainage, and the lengths of hospital stay were observed between the two groups (P < 0.05). Cerebrospinal fluid leakage (n = 2), edema of nerve roots (n = 2), and incision infection (n = 1) were observed in the naked-eye group. There were no complications in the microscopic group, such as cerebrospinal fluid leakage, edema of nerve roots, and incision infection. CONCLUSION: Although microscope-assisted MI-TLIF and naked-eye MI-TLIF are both effective during lumbar revision surgery, microscope-assisted MI-TLIF brings less trauma, less bleeding, shorter postoperative hospital stay, and faster recovery. Unlike traditional surgery, microscope-assisted MI-TLIF provides a clear visual field, adequate hemostasis, and nerve decompression.

Physiological tolerance of black locust (Robinia pseudoacacia L.) and changes of rhizospheric bacterial communities in response to Cd and Pb in the contaminated soil.

Woody plants possess great potential for phytoremediation of heavy metal-contaminated soil. A pot trial was conducted to study growth, physiological response, and Cd and Pb uptake and distribution in black locust (Robinia pseudoacacia L.), as well as the rhizosphere bacterial communities in Cd and Pb co-contaminated soil. The results showed that R. pseudoacacia L. had strong physiological regulation ability in response to Cd and Pb stress in contaminated soil. The total chlorophyll, malondialdehyde (MDA), soluble protein, and sulfhydryl contents, as well as antioxidant enzymes (superoxide dismutase, peroxidase, catalase) activities in R. pseudoacacia L. leaves under the 40 mg·kg-1 Cd and 1000 mg·kg-1 Pb co-contaminated soil were slightly altered. Cd uptake in R. pseudoacacia L. roots and stems increased, while the Pb content in the shoots of R. pseudoacacia L. under the combined Cd and Pb treatments decreased in relative to that in the single Pb treatments. The bacterial α-diversity indices (e.g., Sobs, Shannon, Simpson, Ace, and Chao) of R. pseudoacacia L. rhizosphere soil under Cd and Pb stress were changed slightly relative to the CK treatment. However, Cd and Pb stress could significantly (p < 0.05) alter the rhizosphere soil microbial communities. According to heat map and LEfSe (Linear discriminant analysis Effect Size) analysis, Bacillus, Sphingomonas, Terrabacter, Roseiflexaceae, Paenibacillus, and Myxococcaceae at the genus level were notably (p < 0.05) accumulated in the Cd- and/or Pb-contaminated soil. Furthermore, the MDA content was notably (p < 0.05) negatively correlated with the relative abundances of Isosphaeraceae, Gaiellales, and Gemmatimonas. The total biomass of R. pseudoacacia L. was positively (p < 0.05) correlated with the relative abundances of Xanthobacteraceae and Vicinamibacreraceae. Network analysis showed that Cd and Pb combined stress might enhance the modularization of bacterial networks in the R. pseudoacacia L. rhizosphere soil. Thus, the assembly of the soil bacterial communities in R. pseudoacacia L. rhizosphere may improve the tolerance of plants in response to Cd and/or Pb stress.

Distinct immune escape and microenvironment between RG-like and pri-OPC-like glioma revealed by single-cell RNA-seq analysis.

The association of neurogenesis and gliogenesis with glioma remains unclear. By conducting single-cell RNA-seq analyses on 26 gliomas, we reported their classification into primitive oligodendrocyte precursor cell (pri-OPC)-like and radial glia (RG)-like tumors and validated it in a public cohort and TCGA glioma. The RG-like tumors exhibited wild-type isocitrate dehydrogenase and tended to carry EGFR mutations, and the pri-OPC-like ones were prone to carrying TP53 mutations. Tumor subclones only in pri-OPC-like tumors showed substantially down-regulated MHC-I genes, suggesting their distinct immune evasion programs. Furthermore, the two subgroups appeared to extensively modulate glioma-infiltrating lymphocytes in distinct manners. Some specific genes not expressed in normal immune cells were found in glioma-infiltrating lymphocytes. For example, glial/glioma stem cell markers OLIG1/PTPRZ1 and B cell-specific receptors IGLC2/IGKC were expressed in pri-OPC-like and RG-like glioma-infiltrating lymphocytes, respectively. Their expression was positively correlated with those of immune checkpoint genes (e.g., LGALS33) and poor survivals as validated by the increased expression of LGALS3 upon IGKC overexpression in Jurkat cells. This finding indicated a potential inhibitory role in tumor-infiltrating lymphocytes and could provide a new way of cancer immune evasion.

Influence of structural parameters of 3D-printed triply periodic minimal surface gyroid porous scaffolds on compression performance, cell response, and bone regeneration.

In this study, multi-scale triply periodic minimal surface (TPMS) porous scaffolds with uniform and radial gradient distribution on pore size were printed based on the selective laser melting technology, and the influences of porosity, pore size and radial pore size distribution on compression mechanical properties, cell behavior, and bone regeneration behavior were analyzed. The results showed that the compression performance of the uniform porous scaffolds with high porosity was similar to that of cancellous bone of pig tibia, and the gradient porous scaffolds have higher elastic modulus and compressive toughness. After 4 days of cell culture, cells were distributed on the surface of scaffolds mostly, and the number of adherent cells was higher on the small pore size porous scaffolds; After 7 days, the area and density of cell proliferation on the scaffolds were improved; After 14 days, the cells on the small pore size scaffolds tended to migrate to adjacent pores. Animal implantation experiments showed that collagen fiber osteoid was intermittent on scaffolds with high porosity and large pore size, which was not conducive to bone formation. The appropriate pore size and porosity of bone regeneration were 792 um and 83%, respectively, and the regenerative ability of gradient pore size was better than that of uniform pore size. Our study explains the rules of TPMS gyroid structure parameters on compression performance, cell response and bone regeneration, and provides a reference value for the design of bone repair scaffolds for clinical orthopedics.

Longitudinal SARS-CoV-2 neutralization of Omicron BA.1, BA.5 and BQ.1.1 after four vaccinations and the impact of breakthrough infections in haemodialysis patients.

Background: Individuals on haemodialysis (HD) are more vulnerable to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection than the general population due to end-stage kidney disease-induced immunosuppression. Methods: A total of 26 HD patients experiencing SARS-CoV-2 infection after a third vaccination were matched 1:1 with 26 of 92 SARS-CoV-2-naïve patients by age, sex, dialysis vintage and immunosuppressive drugs receiving a fourth vaccination with a messenger RNA-based vaccine. A competitive surrogate neutralization assay was used to monitor vaccination success. To determine infection neutralization titres, Vero-E6 cells were infected with SARS-CoV-2 variants of concern (VoCs), Omicron sublineage BA.1, BA.5 and BQ.1.1. The 50% inhibitory concentration (IC50, serum dilution factor 1:x) was determined before, 4 weeks after and 6 months after the fourth vaccination. Results: A total of 52 HD patients received four coronavirus disease 2019 (COVID-19) vaccinations and were followed up for a median of 6.3 months. Patient characteristics did not differ between the matched cohorts. Patients without a SARS-CoV-2 infection had a significant reduction of real virus neutralization capacity for all Omicron sublineages after 6 months (P < .001 each). Those patients with a virus infection did not experience a reduction in real virus neutralization capacity after 6 months. Compared with the other Omicron VoC, the BQ.1.1 sublineage had the lowest virus neutralization capacity. Conclusions: SARS-CoV-2-naïve HD patients had significantly decreased virus neutralization capacity 6 months after the fourth vaccination, whereas patients with a SARS-CoV-2 infection had no change in neutralization capacity. This was independent of age, sex, dialysis vintage and immunosuppression. Therefore, in infection-naïve HD patients a fifth COVID-19 vaccination might be reasonable 6 months after the fourth vaccination.

Robotic posterior retroperitoneal adrenalectomy versus laparoscopic posterior retroperitoneal adrenalectomy: outcomes from a pooled analysis.

Background: The comparative advantages of robotic posterior retroperitoneal adrenalectomy (RPRA) over laparoscopic posterior retroperitoneal adrenalectomy (LPRA) remain a topic of ongoing debate within the medical community. This systematic literature review and meta-analysis aim to assess the safety and efficacy of RPRA compared to LPRA, with the ultimate goal of determining which procedure yields superior clinical outcomes. Methods: A systematic search was conducted on databases including PubMed, Embase, Web of Science, and the Cochrane Library database to identify relevant studies, encompassing both randomized controlled trials (RCTs) and non-RCTs, that compare the outcomes of RPRA and LPRA. The primary focus of this study was to evaluate perioperative surgical outcomes and complications. Review Manager 5.4 was used for this analysis. The study was registered with PROSPERO (ID: CRD42023453816). Results: A total of seven non-RCTs were identified and included in this study, encompassing a cohort of 675 patients. The findings indicate that RPRA exhibited superior performance compared to LPRA in terms of hospital stay (weighted mean difference [WMD] -0.78 days, 95% confidence interval [CI] -1.46 to -0.10; p = 0.02). However, there were no statistically significant differences observed between the two techniques in terms of operative time, blood loss, transfusion rates, conversion rates, major complications, and overall complications. Conclusion: RPRA is associated with a significantly shorter hospital stay compared to LPRA, while demonstrating comparable operative time, blood loss, conversion rate, and complication rate. However, it is important to note that further research of a more comprehensive and rigorous nature is necessary to validate these findings. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=453816, identifier CRD42023453816.

Histological characteristics of hair follicles at different hair cycle and in vitro modeling of hair follicle-associated cells of yak (Bos grunniens).

To adapt to the extreme conditions of plateau environments, yaks have evolved thick hair, making them an ideal model for investigating the mechanisms involved in hair growth. We can gain valuable insights into how hair follicles develop and their cyclic growth in challenging environments by studying yaks. However, the lack of essential data on yak hair follicle histology and the absence of in vitro cell models for hair follicles serve as a limitation to such research objectives. In this study, we investigated the structure of skin tissue during different hair follicle cycles using the yak model. Additionally, we successfully established in vitro models of hair follicle-associated cells derived from yak skin, including dermal papilla cells (DPCs), preadipocytes, and fibroblasts. We optimized the microdissection technique for DPCs culture by simplifying the procedure and reducing the time required. Furthermore, we improved the methodology used to differentiate yak preadipocytes into mature adipocytes, thus increasing the differentiation efficiency. The introduction of yak as a natural model provides valuable research resources for exploring the mechanisms of hair growth and contributes to a deeper understanding of hair follicle biology and the development of regenerative medicine strategies.