A minimum functional form of the Escherichia coli BAM complex constituted by BamADE assembles outer membrane proteins in vitro.

The biogenesis of outer membrane proteins is mediated by the ß-barrel assembly machinery (BAM), which is a heteropentomeric complex composed of five proteins named BamA-E in Escherichia coli. Despite great progress in the BAM structural analysis, the molecular details of BAM-mediated processes as well as the exact function of each BAM component during OMP assembly are still not fully understood. To enable a distinguishment of the function of each BAM component, it is the aim of the present work to examine and identify the effective minimum form of the E. coli BAM complex by use of a well-defined reconstitution strategy based on a previously developed versatile assay. Our data demonstrate that BamADE is the core BAM component and constitutes a minimum functional form for OMP assembly in E. coli, which can be stimulated by BamB and BamC. While BamB and BamC have a redundant function based on the minimum form, both together seem to cooperate with each other to substitute for the function of the missing BamD or BamE. Moreover, the BamAE470K mutant also requires the function of BamD and BamE to assemble OMPs in vitro, which vice verse suggests that BamADE are the effective minimum functional form of the E. coli BAM complex.

Signal peptide replacement of Ag43 enables an efficient bacterial cell surface display of receptor-binding domain of coronavirus.

To enable an efficient bacterial cell surface display with effective protein expression and cell surface loading ability via autotransporter for potential vaccine development applications, the inner membrane protein translocation efficiency was investigated via a trial-and-error strategy by replacing the original unusual long signal peptide of E. coli Ag43 with 11 different signal peptides. The receptor-binding domain (RBD) of coronavirus was used as a neutral display substrate to optimize the expression conditions, and the results showed that signal peptides from PelB, OmpC, OmpF, and PhoA protein enhance the bacterial cell surface display efficiency of RBD. In addition, the temperature has also a significant effect on the autodisplay efficiency of RBD. Our data provide further technical basis for the biotechnological application of Ag43 as a bacterial surface display carrier system and further potential application in vaccine development.

Prediction of electrical properties of GAAFET based on integrated learning model.

As device feature sizes continue to decrease and fin field effect transistors reach their physical limits, gate all around field effect transistors (GAAFETs) have emerged with larger gate control areas and stackable characteristics for better suppression of second-order effects such as short-channel effects due to their gate encircling characteristics. Traditional methods for studying the electrical characteristics of devices are mostly based on the technology computer-aided design. Still, it is not conducive to developing new devices due to its time-consuming and inefficient drawbacks. Deep learning (DL) and machine learning (ML) have been well-used in recent years in many fields. In this paper, we propose an integrated learning model that integrates the advantages of DL and ML to solve many problems in traditional methods. This integrated learning model predicts the direct current characteristics, capacitance characteristics, and electrical parameters of GAAFET better than those predicted by DL or ML methods alone, with a linear regression factor (R2) greater than 0.99 and very small root mean square error. The proposed integrated learning model achieves fast and accurate prediction of GAAFET electrical characteristics, which provides a new idea for device and circuit simulation and characteristics prediction in microelectronics.

Prevalence and outcomes of rapidly progressive dementia: a retrospective cohort study in a neurologic unit in China.

BACKGROUND: Rapidly progressive dementia (RPD) is a syndrome originating from various diseases. Recent advances have allowed a better understanding of its categories and spectrum; however, it remains challenging to make an accurate differential diagnosis and prognosis prediction. METHODS: This study was a retrospective evaluation of all participants admitted to the neurology department of a single center in China from January 2015 to December 2019. The screened patients met the RPD criteria and their characteristics were collected to explore a diagnostic pattern of RPD. In addition, outcomes of RPD were evaluated with the Glasgow Outcome Scale (GOS), activities of daily living scale (ADL), and simplified Mini-Mental State Examination (MMSE), and different prognostic analysis methods were performed to determine the prognostic factors of RPD. RESULTS: A total of 149 RPD patients among 15,731 inpatients were identified with an average MMSE value of 13.0 ± 4.6 at baseline. Etiological epidemiology revealed infectious, neurodegenerative and toxic/metabolic diseases as the three largest groups, accounting for 26.2%, 20.8% and 16.8% of all cases, respectively. In particular, prevalence rates of Creutzfeldt-Jakob disease (13.4%), Alzheimer's disease (11.4%), carbon monoxide poisoning (8.1%), neurosyphilis (5.4%) and dementia with Lewy bodies (5.4%) were highest in this series. A recommended diagnostic framework for RPD etiology was thus established. Follow-up evaluations showed a negative correlation between age and GOS scores (r=-0.421, P < 0.001), as well as age and simplified MMSE scores (rs =- 0.393, P < 0.001), and a positive correlation between age and ADL scores (rs =0.503, P < 0.001), and significantly different GOS, ADL and simplified MMSE scores across various etiologies (P = 0.003; F = 9.463, P < 0.001; F = 6.117, P < 0.001). CONCLUSION: Infectious, neurodegenerative and toxic-metabolic entities were the most common RPD categories, and establishing a practical approach to RPD etiology would allow better disease management.

[Clinical and molecular genetic analysis of a case of MEGDEL syndrome].

OBJECTIVE: To explore the clinical and genetic characteristics of a child with MEGDEL syndrome. METHODS: Clinical data of the child was reviewed. Peripheral blood samples of the child and his parents were collected. Mitochondrial genome and the whole exome of the child were analyzed by next-generation sequencing. Candidate variants and its origin were verified by Sanger sequencing and fluorescence quantitative PCR. RESULTS: The patient, a 2-year-and-6-month-old male, has featured hypoglycemia, mental and motor retardation with regression. Cranial MRI showed bilateral putamen damage suggestive of Leigh syndrome. Testing of urine organic acid indicated that the level of 3-methylpentenoic acid was slightly increased. Whole exome sequencing revealed that the child has harbored heterozygous deletion of exons 6 to 17 and c.307A>T nonsense variant of the SERAC1 gene, which were respectively inherited from his parents who were asymptomatic. Treatment with Levocarnitine, vitamin B1, vitamin B2, coenzyme Q10, baclofen and glucuronolactone resulted in improvement of sleep and mental state. CONCLUSION: A case of MEGDEL syndrome without deafness was diagnosed. Discovery of the nonsense mutation and large fragment deletion have enriched the spectrum of SERAC1 gene variants.

Broadband high-resolution microwave frequency measurement based on photonic undersampling via using three cavity-less optical pulse sources with coprime repetition rates.

A photonic-assisted broadband and high-resolution microwave frequency measurement scheme is proposed and demonstrated based on undersampling via using three cavity-less optical pulse sources with coprime repetition rates. After undersampling by three ultrashort pulse trains with repetition rates in the order of gigahertz, input microwave signal is down-converted to three intermediate-frequency (IF) signals located in the first Nyquist frequency range. Through measuring the frequencies of the IF signals via fast Fourier transform after digitization by the commercially available analog-to-digital convertors, the input microwave signal frequency can be retrieved based on the frequency identification algorithm. In the proof-of-concept experiment, three ultrashort pulse trains with repetition rates of 2.99, 3.07, and 3.10 GHz are generated by a cavity-less optical pulse source, where the pulse widths are 9.5, 9.6, and 9.8 ps, respectively. Through using these three ultrashort optical pulse trains, a frequency measurement range up to 40 GHz is realized, where the frequency measurement error is less than ±5kHz, and the spurious-free dynamic range is 91.25dBcHz2/3.

Cross-referenced deadband-free microwave frequency measurement with cascaded-four-wave-mixing-based photonic harmonic down-conversion.

A cross-referenced and deadband-free method with photonic harmonic down-conversion is proposed for microwave frequency measurement based on cascaded-four-wave-mixing (CFWM) in semiconductor optical amplifiers. The proposed method enables ultra-wide and accurate frequency measurement with low-frequency spectrum detection, and at the same time achieves deadband-free and multi-tone frequency measurement by cross-referenced frequency discrimination. For a proof of concept, microwave signal measurement is experimentally demonstrated up to the 40 GHz frequency range with an 0.2-MHz measurement error. The frequency measurement features ease of configuration by only changing the low-frequency electrical local oscillators of the CFWM-based photonic harmonic down-converter.

Optical quantization based on soliton self-frequency shift and a flexible spectrum compression scheme utilizing time-dependent filtering.

We propose and experimentally demonstrate a novel optical spectrum compression scheme utilizing time-dependent filtering effect, which can be used to improve the resolution of the optical quantization based on soliton self-frequency shift (SSFS). The spectrum compression is realized through power-dependent filtering utilizing polarizers and nonlinear polarization rotation effect in a spool of high-nonlinear fiber (HNLF) after mapping the soliton spectrum to the time domain in a section of dispersive fiber. Theoretical analysis and numerical simulation indicate that, compared with the conventional spectrum compression scheme based on chirp compensation, the proposed scheme does not have a restrictive length match requirement of the dispersive fiber and the HNLF. In addition, the output spectral width variation is small for various pulse peak power, which is favorable for the subsequent optical coding. In the experiment, the spectra after SSFS are compressed to an average spectral width of 1.65 nm, which is 45% of that using comb-like fibers. The quantization resolution using the proposed scheme is 5.95 bits for a maximum wavelength shift of 100 nm, which is 1.13 bits higher than that using comb-like fibers.

Self-referenced frequency response measurement of high-speed photodetectors through segmental up-conversion based on low-speed photonic sampling.

A self-referenced electrical method is proposed for measuring the frequency responses of high-speed photodetectors (PDs) through segmental up-conversion based on low-speed photonic sampling. The proposed method provides a very narrow linewidth and ultra-wideband optical stimulus by the segmental electro-optic up-conversion, and eliminates the uneven responses of mode-locked laser diode (MLLD) and electro-optic modulator (MOD) based on the symmetric frequency photonic sampling, which is free of any extra calibration. Moreover, it achieves ultra-wide and scalable frequency response measurement of PDs with 2M-fold measuring frequency range, where the symmetric sweeping frequency up to Nfr/2 of MOD enables the measuring frequency range of M × N×fr. For a proof-of-concept, two commercial PDs are measured with a sampling rate of 96.9 MS/s and a symmetric frequency-swept modulation up to 1.4575 GHz and 2.475 GHz, and their frequency responses are evaluated up to 29.07 GHz (=10 × 30 × fr) and 49.419 GHz (=10 × 51 × fr), respectively. The consistency between our method and conventional methods verifies that the scalable self-referenced measurement provides a simple but accurate method for the performance characterization of high-speed PDs.

Epstein-Barr Virus-Related Post-Transplantation Lymphoproliferative Disorders After Allogeneic Hematopoietic Stem Cell Transplantation.

Epstein-Barr virus (EBV)-related post-transplantation lymphoproliferative disorders (EBV-PTLDs) are rare but potentially fatal complications of allogeneic hematopoietic stem cell transplantation (allo-HSCT), characterized by uncontrolled proliferation of EBV-infected lymphocytes. The most common risk factors include T cell depletion of graft, HLA mismatch, severe graft-versus-host disease (GVHD), and EBV seromismatch (recipient-negative/donor-positive), among others. EBV-PTLDs commonly manifest as fever and lymphadenopathy and may rapidly progress to multiorgan failure and even death. Histopathological evidence is indispensable for the diagnosis, and positive findings of EBV-DNA (EBV-DNAemia) and imaging are also very helpful. Active prophylaxis, such as optimization of the donor choice, conditioning regimen, and GVHD prevention, or passive prophylaxis, such as low dose of rituximab, unselected donor lymphocyte infusion (DLI), and EBV-specific cytotoxic T lymphocyte (EBV-CTLs) infusion, can decrease the incidence of EBV-DNAemia. Rituximab- based preemptive treatment can prevent EBV-DNAemia from developing into EBV-PTLDs, particularly benefiting recipients with higher loads of EBV-DNA, although the long-term outcome has not been significantly improved. To date, there is no consensus as to whether and when to initiate prophylactic or preemptive treatment. The current treatment strategies for probable and proven EBV-PTLDs include reduction of immunosuppression (RI), rituximab, adoptive cell therapy (DLI or EBV-CTLs), chemotherapy, radiotherapy, and surgery, among which rituximab plus RI is the mainstay. However, the mortality of EBV-PTLDs remains considerably high, and novel strategies merit exploration.

Relationship between thrombus composition and prognosis in patients with acute ischemic stroke undergoing mechanical thrombectomy.

BACKGROUND: Mechanical thrombectomy has emerged as the primary endovascular treatment for acute ischemic stroke. Numerous studies have investigated the relationship between thrombus composition and factors such as pharmacological thrombolysis, stroke etiology, mechanical thrombectomy, and radiological imaging. However, limited research has explored the association between thrombus composition and clinical outcomes. METHODS: This retrospective analysis examined the histopathological examination of thrombi retrieved from 50 patients with acute ischemic stroke between May 2020 and May 2023. The composition of the retrieved thrombi was assessed using HE staining to quantify the proportions of red blood cells, white blood cells, platelets, and fibrin. Based on the predominant composition of the thrombus, the patients were divided into two groups: erythrocyte-rich and fibrin-rich. Demographics, clinical characteristics, and clinical outcomes assessed by the National Institutes of Health Stroke Scale (NIHSS) score and modified Rankin Scale (mRS) scores were collected retrospectively. RESULT: Of the 50 patients, 23 were classified in the erythrocyte-rich group, and 27 were classified in the fibrin-rich group. There were no significant differences between the two groups in terms of age, sex, stroke subtype, history of hypertension and diabetes, thrombus location, NIHSS scores, mRS scores on admission, the time interval from symptom onset to hospitalization and reperfusion, or the rate of successful reperfusion. However, erythrocyte-rich thrombi were associated with a shorter time interval from puncture to reperfusion. No significant differences were found in the red blood cell fraction and fibrin/platelet fraction between large artery atherosclerosis and cardioembolism. At the 90-day follow-up, patients with erythrocyte-rich thrombi exhibited lower NIHSS scores and more favorable functional outcomes (mRS scores of 0-2) compared to those with fibrin-rich thrombi. CONCLUSION: Erythrocyte-rich thrombi were linked to shorter time intervals from puncture to reperfusion and favorable clinical outcomes in patients with acute ischemic stroke. The composition of the thrombus may influence the thrombectomy strategy for endovascular therapy.

Lactocaseibacillus rhamnosus zz-1 Supplementation Mitigates Depression-Like Symptoms in Chronic Stress-Induced Depressed Mice via the Microbiota-Gut-Brain Axis.

Accumulating evidence has revealed an association between depression and disordered intestinal microecology. The discovery of psychobiotics has provided a promising perspective for studying the treatment of psychiatric disorders. Here, we aimed to investigate the antidepressant abilities of Lactocaseibacillus rhamnosus zz-1 (LRzz-1) and elucidate the underlying mechanisms. The viable bacteria (2 × 109 CFU/day) were orally supplemented to depressed C57BL/6 mice induced by chronic unpredictable mild stress (CUMS), and the behavioral, neurophysiological, and intestinal microbial effects were assessed, with fluoxetine used as a positive control. The treatment with LRzz-1 effectively mitigated the depression-like behavioral disorders of depressed mice and reduced the expression of inflammatory cytokine mRNA (IL-1ß, IL-6, and TNF-α) in the hippocampus. In addition, LRzz-1 treatment also improved tryptophan metabolic disorder in the mouse hippocampus, as well as its peripheral circulation. These benefits are associated with the mediation of microbiome-gut-brain bidirectional communication. CUMS-induced depression impaired the intestinal barrier integrity and microbial homeostasis in mice, neither of which was restored by fluoxetine. LRzz-1 prevented intestinal leakage and significantly ameliorated epithelial barrier permeability by up-regulating tight-junction proteins (including ZO-1, occludin, and claudin-1). In particular, LRzz-1 improved the microecological balance by normalizing the threatened bacteria (e.g., Bacteroides and Desulfovibrio), exerting beneficial regulation (e.g., Ruminiclostridium 6 and Alispites), and modifying short-chain fatty acid metabolism. In summary, LRzz-1 showed considerable antidepressant-like effects and exhibited more comprehensive intestinal microecological regulation than other drugs, which offers novel insights that can facilitate the development of depression therapeutic strategies.

Effects of microplastics and tetracycline on intestinal injury in mice.

Microplastics (MPs) and tetracycline are both emerging environmental pollutants that threaten human health. The toxic impacts of their single and coexposure on the intestine and gut microbiota have not been well studied in mammals. Given the spatial functional characteristics of the intestine, it is important to know whether the toxicities of MPs and tetracycline in different intestinal segments are distinct. This study investigated the pathological and functional injuries of different intestinal segments and the microbial disorder upon exposure to polystyrene microplastics (PS-MPs) and/or tetracycline hydrochloride (TCH). Both PS-MPs and TCH altered the intestinal morphology and induced functional impairment. However, the PS-MPs primarily damaged the colon, while TCH mainly damaged the small intestine, especially the jejunum. Combined treatment evoked ameliorative adverse effects on the intestinal segments except for the ileum. Gut microbiota analysis revealed that PS-MPs and/or TCH decreased gut microbiota diversity, especially PS-MPs. In addition, PS-MPs and TCH affected the microflora metabolic processes, especially protein absorption and digestion. Gut microbiota dysbiosis could partly lead to the physical and functional damage induced by PS-MPs and TCH. These findings enhance our knowledge regarding the hazards of coexisting microplastics and antibiotics for mammalian intestinal health.

Effect of high-intensity ultrasound on the structural and functional properties of proteins in housefly larvae (Musca demestica).

Insect protein has gradually attracted wide attention from the international research community as a promising source of high-quality protein that can replace traditional protein sources. The larvae of the housefly, a prevalent and widespread species, contain high levels of protein with beneficial properties, namely, anti-fatigue, anti-radiation, and anti-aging functions, as well as liver protection and immunity enhancement. This work thoroughly examined the impact of high-intensity ultrasound (HIUS) on the structural and functional characteristics of housefly larval concentrate protein (HLCP). HLCP samples were sonicated for 20 min at a frequency of 20 kHz with varying energies (0, 100, 200, 300, 400, and 500 W). The findings demonstrated that sonication considerably altered the secondary and tertiary structures of HLCP but had no effect on molecular weight. With an increase in ultrasonic power, HLCP's particle size shrank, more hydrophobic groups were exposed, more free sulfhydryl groups were present, the solution's stability improved, and HLCP's solubility rose. In addition, HLCP's emulsification and foaming abilities were improved by HIUS treatment. It is anticipated that this study's findings will offer fresh insights into the implementation of HLCP in the food sector.

Range of motion of the mid-cervical spine: human versus goat.

BACKGROUND: The goat cervical spine represents a promising alternative for human specimen in spinal implant testing, but the range of motion (ROM) of the spine is lacking. We aimed to evaluate and compare the ROMs of fresh goat and human mid-cervical spine specimens. METHODS: Ten fresh adult healthy male goat cervical spine specimens (G group) and ten fresh frozen adult healthy human cervical spine specimens (average age: 49.5 ± 12.1 years; 6 males, 4 females) (H group) were included. The ROMs of each specimen were biomechanically tested at the C2-3, C3-4, C4-5 and C2-5 levels at 1.5 Nm and 2.5 Nm torque and recorded. The ROMs of different levels of goat cervical samples were compared to those of human cervical samples using an independent sample t test. Significance was defined as a P value of less than 0.05. RESULTS: At the C2-3, C3-4 and C4-5 levels, the ROMs of the goat cervical spine were significantly larger than those of the human cervical spine in all directions except extension under 1.5 Nm torque; under 2.5 Nm torque, the ROMs of the goat cervical spine at the C2-3 and C3-4 levels were significantly larger than those of humans in the pure movement of flexion, lateral bending and axial rotation, and the ROMs for axial rotation of the goat specimens and human specimens were comparable. Under both 1.5 Nm and 2.5 Nm torque, the goat cervical spine displayed a much greater ROM in all directions at the C2-5 level. CONCLUSIONS: Several segmental ROMs of fresh goat and human cervical spine specimens were recorded in this investigation. We recommend using goat cervical specimens as an alternative to fresh human cervical specimens in future studies when focusing only on the ROMs of C2-3, C3-4 and C4-5 in flexion under a torque of 1.5 Nm or the ROMs of C2-3 and C3-4 in flexion and rotation under a torque of 2.5 Nm.

Controlled Synthesis of Lead-Free Double Perovskite Colloidal Nanocrystals for Nonvolatile Resistive Memory Devices.

Although lead-free double perovskites such as Cs2AgBiBr6 have been widely explored, they still remain a daunting challenge for the controlled synthesis of lead-free double perovskite nanocrystals with highly tunable morphology and band structure. Here, we report the controlled synthesis of lead-free double perovskite colloidal nanocrystals including Cs2AgBiBr6 and Cs2AgInxBi1-xBr6 via a facile wet-chemical synthesis method for the fabrication of high-performance nonvolatile resistive memory devices. Cs2AgBiBr6 colloidal nanocrystals with well-defined cuboidal, hexagonal, and triangular morphologies are synthesized through a facile wet-chemical approach by tuning the reaction temperature from 150 to 190 °C. Further incorporating indium into Cs2AgBiBr6 to synthesize alloyed Cs2AgInxBi1-xBr6 nanocrystals not only can induce the indirect-to-direct bandgap transition with enhanced photoluminescence but also can improve its structural stability. After optimizing the active layers and device structure, the fabricated Ag/polymethylene acrylate@Cs2AgIn0.25Bi0.75Br6/ITO resistive memory device exhibits a low power consumption (the operating voltage is ∼0.17 V), excellent cycling stability (>10 000 cycles), and good synaptic property. Our study would enable the facile wet-chemical synthesis of lead-free double perovskite colloidal nanocrystals in a highly controllable manner for the development of high-performance resistive memory devices.

Wavelet power spectrum-based autofocusing algorithm for time delayed and integration charge coupled device space camera.

A novel autofocusing algorithm using the directional wavelet power spectrum is proposed for time delayed and integration charge coupled device (TDI CCD) space cameras, which overcomes the difficulty of focus measure for the real-time change of imaging scenes. Using the multiresolution and band-pass characteristics of wavelet transform to improve the power spectrum based on fast Fourier transform (FFT), the wavelet power spectrum is less sensitive to the variance of scenes. Moreover, the new focus measure can effectively eliminate the impact of image motion mismatching by the directional selection. We test the proposed method's performance on synthetic images as well as a real ground experiment for one TDI CCD prototype camera, and compare it with the focus measure based on the existing FFT spectrum. The simulation results show that the new focus measure can effectively express the defocused states for the real remote sensing images. The error ratio is only 0.112, while the prevalent algorithm based on the FFT spectrum is as high as 0.4. Compared with the FFT-based method, the proposed algorithm performs at a high reliability in the real imaging experiments, where it reduces the instability from 0.600 to 0.161. Two experimental results demonstrate that the proposed algorithm has the characteristics of good monotonicity, high sensitivity, and accuracy. The new algorithm can satisfy the autofocusing requirements for TDI CCD space cameras.

RNF6 Targeted by miR-26a-5p Protects Pancreatic ß-Cell Function Against Type 2 Diabetes.

BACKGROUND: Type 2 diabetes (T2D) is characterized by progressive ß-cell dysfunction. Regulatory microRNAs (miRNAs) may be associated with this. METHODS: Serum miR-26a-5p and RNF6 levels were detected in T2D patients and healthy volunteers via qRT-PCR. Subsequently, the role of specific dysregulated miR-26a-5p or RNF6 in regulating insulin content, cell proliferation, and apoptosis was studied in INS-1 cells. The targeting correlation between miR-26a-5p and RNF6 was detected using a luciferase assay. RESULTS: RNF6 expression was significantly decreased in T2D individuals and INS-1 cells treated with high glucose, while miR-26a-5p expression was increased. In INS-1 cells, RNF6 overexpression or miR-26a-5p downregulation significantly increased insulin content and secretion, induced proliferation, and inhibited apoptosis. RNF6 has been identified as an miR-26a-5p target, which negatively regulates RNF6 to worsen INS-1 cell function. CONCLUSION: RNF6 promoted insulin secretion and induced cell proliferation in INS-1 cells. This may be related to miR-26a-5p targeting and negatively regulating T2D pathogenesis.

Research Progress on Relationship Between Iron Overload and Lower Limb Arterial Disease in Type 2 Diabetes Mellitus.

Iron is one of the most important trace elements in life activities. It participates in a variety of important physiological processes in the body through oxidation-reduction reaction. A large number of studies show that iron overload (IO) is closely related to the progression of diabetes and its various chronic complications. However, the mechanism of iron overload in the pathogenesis of diabetes and the mechanism of iron overload in atherosclerosis (AS) are still controversial, and the relationship between iron overload and diabetic lower extremity arterial disease (LEAD) remains still unclear. Some recent reviews and original research articles suggest further studies to explain the complex relationship between iron metabolism and atherosclerosis. This article reviews the relationship between iron overload and diabetes and its relationship with LEAD, and discusses its mechanisms from various aspects, such as lipid peroxidation induced by iron overload, so as to provide clinical diagnosis and treatment ideas for diabetic lower extremity arterial disease. It is hoped that early evaluation, diagnosis and treatment of LEAD will be inspired.

Multiscale Transcriptomic Integration Reveals B-Cell Depletion and T-Cell Mistrafficking in Nasopharyngeal Carcinoma Progression.

Nasopharyngeal carcinoma (NPC), featured by Epstein-Barr virus (EBV) infection and regional epidemiology, is curable when detected early, but highly lethal at an advanced stage. The molecular mechanism of NPC progression toward a clinically uncontrollable stage remains elusive. In this study, we developed a novel computational framework to conduct multiscale transcriptomic analysis during NPC progression. The framework consists of four modules enabling transcriptomic analyses spanning from single-cell, bulk, microenvironment, to cohort scales. The bulk-transcriptomic analysis of 133 NPC or normal samples unraveled leading functional enrichments of cell-cycle acceleration, epithelial-mesenchymal transition, and chemokine-modulated inflammatory response during NPC progression. The chemokine CXCL10 in the NPC microenvironment, discovered by single-cell RNA sequencing data analysis, recruits cytotoxic T cells through interacting with its receptor CXCR3 at early but late stages. This T-cell mistrafficking was featured by the decline of cytotoxic T cells and the increase of regulatory T cells, accompanied with B-cell depletion confirmed by immunohistochemistry staining. The featured immunomodulatory chemokines were commonly upregulated in the majority of cancers associated with viral or bacterial infections.