Complement system is overactivated in patients with IgA nephropathy after COVID-19.

IgA nephropathy (IgAN), which has been confirmed as a complement mediated autoimmune disease, is also one form of glomerulonephritis associated with COVID-19. Here, we aim to investigate the clinical and immunological characteristics of patients with IgAN after COVID-19. The level of plasma level of C5a (p < 0.001), soluble C5b-9 (p = 0.018), FHR5 (p < 0.001) were all significantly higher in Group CoV (33 patients with renal biopsy-proven IgAN experienced COVID-19) compared with Group non-CoV (44 patients with IgAN without COVID-19), respectively. Compared with Group non-CoV, the intensity of glomerular C4d (p = 0.017) and MAC deposition (p < 0.001) and Gd-IgA1 deposition (p = 0.005) were much stronger in Group CoV. Our finding revealed that for IgAN after COVID-19, mucosal immune responses to SARS-CoV-2 infection may result in the overactivation of systemic and renal local complement system, and increased glomerular deposition of Gd-IgA1, which may lead to renal dysfunction and promote renal progression in IgAN patients.

Revisiting the critical roles of reactive astrocytes in neurodegeneration.

Astrocytes, an integral component of the central nervous system (CNS), contribute to the maintenance of physiological homeostasis through their roles in synaptic function, K+ buffering, blood-brain barrier (BBB) maintenance, and neuronal metabolism. Reactive astrocytes refer to astrocytes undergoing morphological, molecular and functional remodelling in response to pathological stimuli. The activation and differentiation of astrocytes are implicated in the pathogenesis of multiple neurodegenerative diseases. However, there are still controversies regarding their subset identification, function and nomenclature in neurodegeneration. In this review, we revisit the multidimensional roles of reactive astrocytes in Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), multiple sclerosis (MS) and amyotrophic lateral sclerosis (ALS). Furthermore, we propose a precise linkage between astrocyte subsets and their functions based on single-cell sequencing analyses.

Friend or foe: role of pathological tau in neuronal death.

Neuronal death is one of the most common pathological hallmarks of diverse neurological diseases, which manifest varying degrees of cognitive or motor dysfunction. Neuronal death can be classified into multiple forms with complicated and unique regulatory signaling pathways. Tau is a key microtubule-associated protein that is predominantly expressed in neurons to stabilize microtubules under physiological conditions. In contrast, pathological tau always detaches from microtubules and is implicated in a series of neurological disorders that are characterized by irreversible neuronal death, such as necrosis, apoptosis, necroptosis, pyroptosis, ferroptosis, autophagy-dependent neuronal death and phagocytosis by microglia. However, recent studies have also revealed that pathological tau can facilitate neuron escape from acute apoptosis, delay necroptosis through its action on granulovacuolar degeneration bodies (GVBs), and facilitate iron export from neurons to block ferroptosis. In this review, we briefly describe the current understanding of how pathological tau exerts dual effects on neuronal death by acting as a double-edged sword in different neurological diseases. We propose that elucidating the mechanism by which pathological tau affects neuronal death is critical for exploring novel and precise therapeutic strategies for neurological disorders.

In vivo imaging of astrocytes in the whole brain with engineered AAVs and diffusion-weighted magnetic resonance imaging.

Astrocytes constitute a major part of the central nervous system and the delineation of their activity patterns is conducive to a better understanding of brain network dynamics. This study aimed to develop a magnetic resonance imaging (MRI)-based method in order to monitor the brain-wide or region-specific astrocytes in live animals. Adeno-associated virus (AAVs) vectors carrying the human glial fibrillary acidic protein (GFAP) promoter driving the EGFP-AQP1 (Aquaporin-1, an MRI reporter) fusion gene were employed. The following steps were included: constructing recombinant AAV vectors for astrocyte-specific expression, detecting MRI reporters in cell culture, brain regions, or whole brain following cell transduction, stereotactic injection, or tail vein injection. The astrocytes were detected by both fluorescent imaging and Diffusion-weighted MRI. The novel AAV mutation (Site-directed mutagenesis of surface-exposed tyrosine (Y) residues on the AAV5 capsid) significantly increased fluorescence intensity (p < 0.01) compared with the AAV5 wild type. Transduction of the rAAV2/5 carrying AQP1 induced the titer-dependent changes in MRI contrast in cell cultures (p < 0.05) and caudate-putamen (CPu) in the brain (p < 0.05). Furthermore, the MRI revealed a good brain-wide alignment between AQP1 levels and ADC signals, which increased over time in most of the transduced brain regions. In addition, the rAAV2/PHP.eB serotype efficiently introduced AOP1 expression in the whole brain via tail vein injection. This study provides an MRI-based approach to detect dynamic changes in astrocytes in live animals. The novel in vivo tool could help us to understand the complexity of neuronal and glial networks in different pathophysiological conditions.

Social isolation reinforces aging-related behavioral inflexibility by promoting neuronal necroptosis in basolateral amygdala.

Aging is characterized with a progressive decline in many cognitive functions, including behavioral flexibility, an important ability to respond appropriately to changing environmental contingencies. However, the underlying mechanisms of impaired behavioral flexibility in aging are not clear. In this study, we reported that necroptosis-induced reduction of neuronal activity in the basolateral amygdala (BLA) plays an important role in behavioral inflexibility in 5-month-old mice of the senescence-accelerated mice prone-8 (SAMP8) line, a well-established model with age-related phenotypes. Application of Nec-1s, a specific inhibitor of necroptosis, reversed the impairment of behavioral flexibility in SAMP8 mice. We further observed that the loss of glycogen synthase kinase 3α (GSK-3α) was strongly correlated with necroptosis in the BLA of aged mice and the amygdala of aged cynomolgus monkeys (Macaca fascicularis). Moreover, genetic deletion or knockdown of GSK-3α led to the activation of necroptosis and impaired behavioral flexibility in wild-type mice, while the restoration of GSK-3α expression in the BLA arrested necroptosis and behavioral inflexibility in aged mice. We further observed that GSK-3α loss resulted in the activation of mTORC1 signaling to promote RIPK3-dependent necroptosis. Importantly, we discovered that social isolation, a prevalent phenomenon in aged people, facilitated necroptosis and behavioral inflexibility in 4-month-old SAMP8 mice. Overall, our study not only revealed the molecular mechanisms of the dysfunction of behavioral flexibility in aged people but also identified a critical lifestyle risk factor and a possible intervention strategy.

Long noncoding RNA as a potential diagnostic tool for prostate cancer: a systematic review and meta-analysis.

PURPOSE: To identify consistently expressed lncRNAs and suitable lncRNAs with high sensitivity and specificity from multiple independent studies as potential biomarkers for PCa diagnostics. METHODS: We searched multiple electronic databases including PubMed, Web of Science, EMBASE, Cochrane Library, CNKI, CQVIP, Wanfang, and CBMdisc for studies published up to July 2022. The quality of the included studies was assessed by two independent reviewers based on the QUADAS-2 tool using Review Manager 5.3. A vote-counting method was used based on the ranking of potential molecular biomarkers. The top-ranked lncRNAs were further assessed for diagnostic value using Meta-disc version 1.4 software. RESULTS: Among the 26 included studies, 2 circulating lncRNAs (PCA3 and MALAT-1) were reported 3 or more times in PCa patients versus non-PCa patients. In further analysis, the areas under the curve of the summary receiver operating characteristic curves for PCA3 and MALAT-1 distinguishing PCa patients were 0.775 and 0.771, respectively. CONCLUSIONS: Based on the current evidence, PCA3 and MALAT-1 are reliable lncRNAs for the diagnosis of PCa.

Angularly Cascaded Long-Period Fiber Grating for Curvature and Temperature Detection.

A high-sensitivity curvature sensor with dual-parameter measurement ability based on angularly cascaded long-period fiber grating (AC-LPFG) is proposed and experimentally demonstrated, which consists of two titled LPFGs (TLPFGs) with different tilt angles and the same grating period. AC-LPFG was fabricated by using a deep ultraviolet laser and an amplitude-mask in our laboratory. The experimental results show that simultaneous measurement of curvature and temperature can be achieved by monitoring the wavelengths of two resonant peaks for different TLPFGs. The two peaks show opposite shifts with increasing curvature and has a maximum curvature sensitivity of 16.392 nm/m-1. With the advantages of low cost, high sensitivity, and dual-parameter measurements, our sensor has more potential for engineering applications.

Review on recent progress in on-line monitoring technology for atmospheric pollution source emissions in China.

Emissions from mobile sources and stationary sources contribute to atmospheric pollution in China, and its components, which include ultrafine particles (UFPs), volatile organic compounds (VOCs), and other reactive gases, such as NH3 and NOx, are the most harmful to human health. China has released various regulations and standards to address pollution from mobile and stationary sources. Thus, it is urgent to develop online monitoring technology for atmospheric pollution source emissions. This study provides an overview of the main progress in mobile and stationary source monitoring technology in China and describes the comprehensive application of some typical instruments in vital areas in recent years. These instruments have been applied to monitor emissions from motor vehicles, ships, airports, the chemical industry, and electric power generation. Not only has the level of atmospheric environment monitoring technology and equipment been improving, but relevant regulations and standards have also been constantly updated. Meanwhile, the developed instruments can provide scientific assistance for the successful implementation of regulations. According to the potential problem areas in atmospheric pollution in China, some research hotspots and future trends of atmospheric online monitoring technology are summarized. Furthermore, more advanced atmospheric online monitoring technology will contribute to a comprehensive understanding of atmospheric pollution and improve environmental monitoring capacity.

Effects of penehyclidine hydrochloride on myocardial ischaemia-reperfusion injury in rats by inhibiting TLR4/MyD88/NF-κB pathway via miR-199a-3p.

This study was to probe the role of penehyclidine hydrochloride (PHC) mediating the impact of toll-like receptor 4 (TLR4)/myeloid differentiation factor 88 (MyD88)/nuclear factor-kappa B (NF-κB) signalling pathway on myocardial ischaemia-reperfusion injury (MI/RI) in rats through miR-199a-3p. The rat MI/RI model was established through ligating left anterior descending (LAD) coronary artery. PHC was injected preoperatively into the model rats, and injected with miR-199a-3p lentiviral vector or TLR4 antagonist (TAK-242). Next, cardiac function of rats was examined by echocardiography, and rat serum indicators, oxidative stress levels and inflammatory factors were detected. HE staining was applied to detect pathological tissue structure, TUNEL staining to detect apoptosis rate, qRCR and western blot to detect miR-199a-3p and TLR4/MyD88/NF-κB expressions in rat myocardial tissues. Dual luciferase reporter experiment was conducted to confirm the relationship between miR-199a-3p and TLR4. In conclusion, PHC suppresses TLR4/MyD88/NF-κB signalling pathway through miR-199a-3p, thereby improving MI/RI in rats.

Low bending loss few-mode hollow-core anti-resonant fiber with glass-sheet conjoined nested tubes.

A novel hollow-core anti-resonant fiber (HC-ARF) with glass-sheet conjoined nested tubes that supports five core modes of LP01-LP31 with low mode couplings, large differential group delays (DGDs), and low bending losses (BLs) is proposed. A novel cladding structure with glass-sheet conjoined nested tubes (CNT) is induced for the proposed HC-ARF which can suppress mode couplings between the LP01-LP31 modes and the cladding modes. The higher-order modes (HOMs) which are LP11-LP31 modes also have very low loss by optimizing the radius of the nested tube and the core radius. Moreover, the large effective refractive index differences Δneff between HOMs are all larger than 1 × 10-4 which contributes to a large DGD in the wavelength range from 1.3 to 1.7 µm. The bending loss of the HC-ARF is analyzed and optimized emphatically. Our calculation results show that bending losses of LP01-LP31 modes are all lower than 3.0 × 10-4 dB/m in the wavelength range from 1.4 to 1.61 µm even when the fiber bending radius of the HC-ARF is 6 cm.

Shortwave infrared single-pixel spectral imaging based on a GSST phase-change metasurface.

Shortwave infrared (SWIR) spectral imaging obtains spectral fingerprints corresponding to overtones of molecular vibrations invisible to conventional silicon-based imagers. However, SWIR imaging is challenged by the excessive cost of detectors. Single-pixel imaging based on compressive sensing can alleviate the problem but meanwhile presents new difficulties in spectral modulations, which are prerequisite in compressive sampling. In this work, we theoretically propose a SWIR single-pixel spectral imaging system with spectral modulations based on a Ge2Sb2Se4Te1 (GSST) phase-change metasurface. The transmittance spectra of the phase-change metasurface are tuned through wavelength shifts of multipole resonances by varying crystallinities of GSST, validated by the multipole decompositions and electromagnetic field distributions. The spectral modulations constituted by the transmittance spectra corresponding to the 11 phases of GSST are sufficient for the compressive sampling on the spectral domain of SWIR hyperspectral images, indicated by the reconstruction in false color and point spectra. Moreover, the feasibility of optimization on phase-change metasurface via coherence minimization is demonstrated through the designing of the GSST pillar height. The concept of spectral modulation with phase-change metasurface overcomes the static limitation in conventional modulators, whose integratable and reconfigurable features may pave the way for high-efficient, low-cost, and miniaturized computational imaging based on nanophotonics.

Design of an ultra-broadband optical filter based on a local micro-structured long period fiber grating near PMTP.

This paper presents a local micro-structured long period fiber grating (LMS-LPFG) ultra-broadband optical filter based on the wide bandwidth near the phase-matching turning point (PMTP). The structure of LMS-LPFG is obtained by dividing a LPFG into two parts of equal length and reducing the cladding radius of the second LPFG. At this time, the LMS-LPFG can be regarded as a cascade of two equal-length LPFGs with different resonance wavelengths. The cladding mode and grating period are determined to make the first LPFG work in the double-peak resonance state, and the second LPFG operates near PMTP. It is found that the transmission spectra of the two LPFGs can be superimposed to form a wide loss bandwidth. Then the cladding radii of the second LPFG and grating structure parameters are designed based on coupled-mode theory. First, the grating period corresponding to the operating wavelength is determined from the phase-matching curve of LMS-LPFG. Then, the radius of the second LPFG with a designated grating period is selected to make LPFG 2 work in PMTP by reducing its cladding radius. In addition, the grating lengths of the two LPFGs are determined by maximizing the loss of the LMS-LPFG's transmission spectrum. Finally, the two LPFGs are cascaded into a LMS-LPFG, and the optical transmission spectrum of the LMS-LPFG is calculated by the transfer matrix method. Simulation results show that the bandwidth of the transmission spectrum can reach 380 nm. In addition, the flexibility of design for the operating wave band is discussed and confirmed, and can meet different actual requirements of optical communication.

NEXMIF/KIDLIA Knock-out Mouse Demonstrates Autism-Like Behaviors, Memory Deficits, and Impairments in Synapse Formation and Function.

Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disability that demonstrates impaired social interactions, communication deficits, and restrictive and repetitive behaviors. ASD has a strong genetic basis and many ASD-associated genes have been discovered thus far. Our previous work has shown that loss of expression of the X-linked gene NEXMIF/KIDLIA is implicated in patients with autistic features and intellectual disability (ID). To further determine the causal role of the gene in the disorder, and to understand the cellular and molecular mechanisms underlying the pathology, we have generated a NEXMIF knock-out (KO) mouse. We find that male NEXMIF KO mice demonstrate reduced sociability and communication, elevated repetitive grooming behavior, and deficits in learning and memory. Loss of NEXMIF/KIDLIA expression results in a significant decrease in synapse density and synaptic protein expression. Consistently, male KO animals show aberrant synaptic function as measured by excitatory miniatures and postsynaptic currents in the hippocampus. These findings indicate that NEXMIF KO mice recapitulate the phenotypes of the human disorder. The NEXMIF KO mouse model will be a valuable tool for studying the complex mechanisms involved in ASD and for the development of novel therapeutics for this disorder.SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder characterized by behavioral phenotypes. Based on our previous work, which indicated the loss of NEXMIF/KIDLIA was associated with ASD, we generated NEXMIF knock-out (KO) mice. The NEXMIF KO mice demonstrate autism-like behaviors including deficits in social interaction, increased repetitive self-grooming, and impairments in communication and in learning and memory. The KO neurons show reduced synapse density and a suppression in synaptic transmission, indicating a role for NEXMIF in regulating synapse development and function. The NEXMIF KO mouse faithfully recapitulates the human disorder, and thus serves as an animal model for future investigation of the NEXMIF-dependent neurodevelopmental disorders.

Identification of the downstream molecules of agrin/Dok-7 signaling in muscle.

The development of the neuromuscular junction depends on signaling processes that involve protein phosphorylation. Motor neuron releases agrin to activate muscle protein Dok-7, a key tyrosine kinase essential for the formation of a mature and functional neuromuscular junction. However, the signaling cascade downstream of Dok-7 remains poorly understood. In this study, we combined the clustered regularly interspaced short palindromic repeats/Cas9 technique and quantitative phosphoproteomics analysis to study the tyrosine phosphorylation events triggered by agrin/Dok-7. We found tyrosine phosphorylation level of 36 proteins increased specifically by agrin stimulation. In Dok-7 mutant myotubes, however, 13 of the 36 proteins failed to be enhanced by agrin stimulation, suggesting that these 13 proteins are Dok-7-dependent tyrosine-phosphorylated proteins, could work as downstream molecules of agrin/Dok-7 signaling. We validated one of the proteins, Anxa3, by in vitro and in vivo assays. Knocking down of Anxa3 in the cultured myotubes inhibited agrin-induced AChR clustering, whereas reduction of Anxa3 in mouse muscles induced abnormal postsynaptic development. Collectively, our phosphoproteomics analysis provides novel insights into the complicated signaling network downstream of agrin/Dok-7.

Association of HECW2 variants with developmental and epileptic encephalopathy and knockdown of zebrafish hecw2a.

Developmental and epileptic encephalopathy (DEE) is a severe encephalopathy in infants and early childhood. In this study we reported a recurrent de novo variant (c.3985C>T, p.R1330W) in HECW2 (HECT, C2 and WW domain containing E3 ubiquitin protein ligase 2) (MIM# 617245) identified by screening 240 patients with DEE and summarized clinical features of published DEE patients with HECW2 variants. Functionally, transcriptional knockdown of zebrafish hecw2a led to early morphological abnormalities in the brain tissues. These results suggest a potential functional link between HECW2 dysfunction and brain development.

Recent advances in ultrasound in the diagnosis and evaluation of the activity of hepatic alveolar echinococcosis.

Echinococcosis is a worldwide neglected zoonotic disease. Alveolar echinococcosis (AE) poses a more serious threat to life and health than cystic echinococcosis, and has been one of the world's most lethal chronic parasitosis. Assessment of metacestode activity status is essential for individual treatment strategy design for a given AE patient, and fluorodeoxyglucose positron-emission tomography (FDG-PET) has been the gold standard. In this study, we reviewed previous evidence on AE activity assessment using contrast-enhanced ultrasound (CEUS), and its comparison with FDG-PET. The results showed good consistency between them, indicating CEUS as a suitable substitute for FDG-PET. With its advantage as being readily portable, widely available, and not costly, CEUS is more suitable for use in the developing countries and rural areas.

Correcting abnormalities in miR-124/PTPN1 signaling rescues tau pathology in Alzheimer's disease.

MicroRNAs have been implicated in diverse physiological and pathological processes. We previously reported that aberrant microRNA-124 (miR-124)/non-receptor-type protein phosphatase 1 (PTPN1) signaling plays an important role in the synaptic disorders associated with Alzheimer's disease (AD). In this study, we further investigated the potential role of miR-124/PTPN1 in the tau pathology of AD. We first treated the mice with intra-hippocampal stereotactic injections. Then, we used quantitative real-time reverse transcription PCR (qRT-PCR) to detect the expression of microRNAs. Western blotting was used to measure the level of PTPN1, the level of tau protein, the phosphorylation of tau at AD-related sites, and alterations in the activity of glycogen synthase kinase 3ß (GSK-3ß) and protein phosphatase 2 (PP2A). Immunohistochemistry was also used to detect changes in tau phosphorylation levels at AD-related sites and somadendritic aggregation. Soluble and insoluble tau protein was separated by 70% formic acid (FA) extraction to examine tau solubility. Finally, behavioral experiments (including the Morris water maze, fear conditioning, and elevated plus maze) were performed to examine learning and memory ability and emotion-related behavior. We found that artificially replicating the abnormalities in miR-124/PTPN1 signaling induced AD-like tau pathology in the hippocampus of wild-type mice, including hyperphosphorylation at multiple sites, insolubility and somadendritic aggregation, as well as learning/memory deficits. We also found that disruption of miR-124/PTPN1 signaling was caused by the loss of RE1-silencing transcription factor protein, which can be initiated by Aß insults or oxidative stress, as observed in the brains of P301S mice. Correcting the deregulation of miR-124/PTPN1 signaling rescued the tau pathology and learning/memory impairments in the P301S mice. We also found that miR-124/PTPN1 abnormalities induced activation of glycogen synthase kinase 3 (GSK-3) and inactivation of protein phosphatase 2A (PP2A) by promoting tyrosine phosphorylation, implicating an imbalance in tau kinase/phosphatase. Thus, targeting the miR-124/PTPN1 signaling pathway is a promising therapeutic strategy for AD.

miR-214-3p Targets ß-Catenin to Regulate Depressive-like Behaviors Induced by Chronic Social Defeat Stress in Mice.

ß-Catenin has been implicated in major depressive disorder (MDD), which is associated with synaptic plasticity and dendritic arborization. MicroRNAs (miRNA) are small noncoding RNAs containing about 22 nucleotides and involved in a variety of physiological and pathophysiological process, but their roles in MDD remain largely unknown. Here, we investigated the expression and function of miRNAs in the mouse model of chronic social defeat stress (CSDS). The regulation of ß-catenin by selected miRNA was validated by silico prediction, target gene luciferase reporter assay, and transfection experiment in neurons. We demonstrated that the levels of miR-214-3p, which targets ß-catenin transcripts were significantly increased in the medial prefrontal cortex (mPFC) of CSDS mice. Antagomir-214-3p, a neutralizing inhibitor of miR-214-3p, increased the levels of ß-catenin and reversed the depressive-like behavior in CSDS mice. Meanwhile, antagomir-214-3p increased the amplitude of miniature excitatory postsynaptic current (mEPSC) and the number of dendritic spines in mPFC of CSDS mice, which may be related to the elevated expression of cldn1. Furthermore, intranasal administered antagomir-214-3p also significantly increased the level of ß-catenin and reversed the depressive-like behaviors in CSDS mice. These results may represent a new therapeutic target for MDD.

Design of a narrow-bandwidth refractive index sensor based on a cascaded few-mode long-period fiber grating.

This work presents a design of a cascaded few-mode long-period fiber grating (FM-CLPFG) refractive index sensor with a narrow bandwidth that is based on the feature of narrow-bandwidth loss peak of few-mode long-period fiber grating (FM-LPFG) and that further reduces the loss-peak bandwidth of a single FM-LPFG by cascading. On the basis of the coupled-mode theory of FM-LPFG, the mutual interference between the loss peaks of each mode is reduced, and the loss-peak coupling intensity is ensured by selecting the appropriate grating period and grating length. Furthermore, the influence of the cascaded fiber length and the number of cascaded grating segments on the loss-peak bandwidth are analyzed. Based on the above designed parameters, the FM-CLPFG narrow-bandwidth sensor with a bandwidth of about 1 nm is designed. The results show that the sensitivity of this sensor is available to 2410 nm/RIU, with the surrounding refractive index changing from 1.4445 to 1.4475.

Fast measurement of the laser beam quality factor based on phase retrieval with a liquid lens.

In this paper, a new method for measuring the beam quality (M2) of lasers based on phase retrieval with a liquid lens is proposed. With intensity profiles obtained under different focal lengths in a certain position, a variable-focus iterative retrieval algorithm is established for the reconstruction of the complex amplitude. Then M2 can be calculated with the angular spectrum theory. Feasibility of the proposed method is demonstrated with single- and multimode lasers through both simulations and experiments. Compared with the traditional liquid lens method, the M2 of lasers can be measured faster with the proposed method.