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Emerging studies reported that gut microbiota and fecal metabolites take part in major depressive disorder (MDD) pathogenesis. However, the conclusions based on a single depressive animal model seem inconsistent or even controversial.Multiple depression rat models, including chronic unpredictable mild stress, chronic restraint stress, social defeat, and learned helplessness, were used. Then, the 16S ribosomal RNA gene sequencing and liquid chromatography-mass spectrometry analysis determined the alteration of gut microbiota and fecal metabolites.The results of sucrose preference test and forced swimming test suggested that each model successfully established depression-like behavior. A total of 179 discriminative amplicon sequence variants (ASVs) were identified among four models. The overall discriminative ASVs mainly belonged to the family Lachnospiraceae, Muribaculaceae, and Oscillospiraceae. Moreover, the fecal metabolomic analysis identified 468 differential expressed metabolites. Among all the differential metabolites, 11 specific pathways significantly altered, which were mainly belonged to lipid and amino acid metabolism. Finally, co-occurrence network analysis suggested that target differential metabolites were associated with discriminative ASVs mainly assigned to family taxon Lachnospiraceae, Muribaculaceae, and Oscillospiraceae.The heterogeneity of MDD in humans cannot be totally imitated by animal models.In multiple depression models, the alterations of family Lachnospiraceae, Muribaculaceae, and Oscillospiraceae with the dysbiosis of lipid and amino acid metabolism were gut microbiota and fecal metabolome features. The findings of our research may help us to have a comprehensive understanding of gut microbiota and fecal metabolome in depression.

Kidney fibrosis is associated with the progression of acute kidney injury to chronic kidney disease. MG53, a cell membrane repair protein, has been shown to protect against injury to kidney epithelial cells and acute kidney injury. Here, we evaluated the role of MG53 in modulation of kidney fibrosis in aging mice and in mice with unilateral ureteral obstruction (UUO) a known model of progressive kidney fibrosis. Mice with ablation of MG53 developed more interstitial fibrosis with age than MG53-intact mice of the same age. Similarly, in the absence of MG53, kidney fibrosis was exaggerated compared to mice with intact MG53 in the obstructed kidney compared to the contralateral unobstructed kidney or the kidneys of sham operated mice. The ureteral obstructed kidneys from MG53 deficient mice also showed significantly more inflammation than ureteral obstructed kidneys from MG53 intact mice. In vitro experiments demonstrated that MG53 could enter the nuclei of proximal tubular epithelial cells and directly interact with the p65 component of transcription factor NF-κB, providing a possible explanation of enhanced inflammation in the absence of MG53. To test this, enhanced MG53 expression through engineered cells or direct recombinant protein delivery was given to mice subject to UUO. This reduced NF-κB activation and inflammation and attenuated kidney fibrosis. Thus, MG53 may have a therapeutic role in treating chronic kidney inflammation and thereby provide protection against fibrosis that leads to the chronic kidney disease phenotype.

Artificial bee colony (ABC) algorithm is a relatively new paradigm of swarm intelligence based optimization technique, which has attracted a lot of attention for its simple structure and good performance. For some complex optimization problems, however, the performance of ABC is challenged due to its solution search equation that has strong explorative ability but poor exploitative ability. To solve this defect, in this work, we propose an improved ABC algorithm by using multi-elite guidance, which has the benefits of utilizing valuable information from elite individuals to guide search while without losing population diversity. First, we construct an elite group by selecting some elite individuals, and then introduce two improved solution search equations into the employed bee phase and onlooker bee phase based on the elite group, respectively. Last, we develop a modified neighborhood search operator by utilizing the elite group as well, which aims to achieve a better tradeoff between explorative and exploitative abilities. To verify our approach, 50 well-known test functions and one real-world optimization problem are used in the experiments, including 22 scalable basic test functions and 28 complex CEC2013 test functions. Seven different well-established ABC variants are involved in the comparison and the results show that our approach can achieve better or at least comparable performance on most of the test functions.

Artificial bee colony (ABC) and its most modifications use a probability method to select good food sources (called solutions) in the onlooker bee search phase. However, the probability selection does not work with increasing of iterations, because the fitness values cannot be used to distinguish two different solutions. In order to tackle this problem, this paper proposes a new ABC (called NSABC), in which a new selection method based on neighborhood radius is used. Unlike the probability selection in the original ABC, NSABC chooses the best solution in the neighborhood radius to generate offspring. Based on the neighborhood radius, two new solution search strategies are modified. The scout bee search phase is improved by using opposition-based learning and the neighborhood radius. To evaluate the search ability of NSABC, there are 22 benchmark problems used in the experiments. Performance comparison shows NSABC achieves better results than five other ABC algorithms.

1-nitropyrene (1-NP) is representative nitropolycyclic aromatic hydrocarbon pollutant widely present in exhaust particles of internal combustion engine, which is known for its carcinogenicity and mutagenicity. Previous studies have demonstrated that 1-NP has reproductive toxicity, but the specific mechanism is unknown. In this study, Human decidual stromal cells (HDSCs) were treated by 1-NP, exosomes were extracted from the conditioned medium of HDSCs, which were then used to treat human chorionic trophoblast cells (HTR8/SVneo) for 24 h. The findings showed that human decidual stromal cell-derived exosomes (HDSC-EXOs) can promote the proliferation, migration, invasion and epithelial-mesenchymal transition (EMT; Vimentin and N-cadherin) of HTR8/SVneo by about 64%, 17%, 23%, 81% and 13%. The process of regulating the biological behaviors of embryonic trophoblast cells by maternal decidual stromal cells during pregnancy was simulated. Further investigations showed that HDSC-EXOs treatment activated the Wnt/β-catenin signaling pathway in HTR8/SVneo. Co-treatment by dickkopf-1 (DKK-1) significantly suppressed the activation of Wnt/β-catenin signaling pathway in HTR8/SVneo, and inhibited the proliferation, migration, invasion and EMT (N-cadherin and E-cadherin) of HTR8/SVneo by about 60%, 22%, 42%, 25%, 55% and 21%. These findings indicated that 1-NP exposure could induce the secretion of HDSC-EXOs from HDSCs, which in turn activate the Wnt/β-catenin signaling pathway and enhance the proliferation, migration, invasion and EMT of HTR8/SVneo.

MicroRNA (miRNA), as one of the ideal target biomarker analytes, plays an essential role in biological processes; thus, the development of rapidly sensitive detection methods is imperative. Herein, we proposed a pump-free surface-enhanced Raman scatting (SERS) microfluidic chip for the rapid and ultrasensitive detection of miR-106b and miR-196b, laryngeal squamous cell carcinoma (LSCC)-related miRNAs. Ag-Au core-shell nanorods (Ag-AuNRs) were applied to prepare SERS tags by modifying Raman reporters and hairpin DNAs. The capture probes were synthesized by labeling hairpin DNAs onto the magnetic beads (MBs) surface. In the presence of targets, the catalytic hairpin assembly (CHA) reactions between SERS tags and capture probes could be triggered, causing the aggregation of Ag-AuNRs. The tiny magnets installed under the rectangular chamber could magnetically gather the CHA products, leading to the further aggregation of Ag-AuNRs. Thus, this strategy could achieve the double aggregation of Ag-AuNRs, resulting in the significant amplification of the SERS signal. The proposed strategy achieved simultaneous and sensitive detection of miR-106b and miR-196b, with limits of detection low to aM level. The whole detection process could be completed within 5 min. Moreover, this microfluidic chip exhibited excellent reproducibility, stability, and specificity. The high accuracy of this SERS microfluidic chip was proved by practical analysis in LSCC patients' serum. The results demonstrated that SERS could be a promising alternative clinical diagnosis tool and exhibited potential application for the dynamic monitoring of cancer staging.

Ischemic injury to the heart induces mitochondrial dysfunction due to increasing oxidative stress. MG53, also known as TRIM72, is highly expressed in striated muscle, is secreted as a myokine after exercise, and is essential for repairing damaged plasma membrane of many tissues by interacting with the membrane lipid phosphatidylserine (PS). We hypothesized MG53 could preserve mitochondrial integrity after an ischemic event by binding to the mitochondrial-specific lipid, cardiolipin (CL), for mitochondria protection to prevent mitophagy. Fluorescent imaging and Western blotting experiments showed recombinant human MG53 (rhMG53) translocated to the mitochondria after ischemic injury in vivo and in vitro. Fluorescent imaging indicated rhMG53 treatment reduced superoxide generation in ex vivo and in vitro models. Lipid-binding assay indicated MG53 binds to CL. Transfecting cardiomyocytes with the mitochondria-targeted mt-mKeima showed inhibition of mitophagy after MG53 treatment. Overall, we show that rhMG53 treatment may preserve cardiac function by preserving mitochondria in cardiomyocytes. These findings suggest MG53's interactions with mitochondria could be an attractive avenue for developing MG53 as a targeted protein therapy for cardioprotection.

TP53-induced glycolysis and apoptosis regulator (TIGAR) alleviates oxidative stress and protects against ischemic neuronal injury by shifting glucose metabolism into the pentose phosphate pathway (PPP). However, the brain alters glucose metabolism from PPP to glycolysis during prolonged ischemia. It is still unknown whether and how TIGAR exerts the antioxidant activity and neuroprotection in prolonged ischemic brains. Here, we determined the significant upregulation of TIGAR that was proportional to the duration of ischemia. However, TIGAR failed to upregulate the NADPH level but still alleviated oxidative stress in neuronal cells with prolonged oxygen glucose-deprivation (OGD). Furthermore, inhibiting PPP activity, either by the expression of mutant TIGAR (which lacks enzymatic activity) or by silencing Glucose 6-phosphate dehydrogenase, still retained antioxidant effects and neuroprotection of TIGAR with prolonged OGD. Intriguingly, TIGAR-induced autophagy alleviated oxidative stress, contributing to neuron survival. Further experiments indicated that TIGAR-induced autophagy neutralized oxidative stress by activating Nrf2, which was cancelled by ML385 or Nrf2 knockdown. Remarkably, either Atg7 deletion or Nrf2 silencing abolished the neuroprotection of TIGAR in mice with prolonged ischemia. Taken together, we found a PPP-independent pathway in which TIGAR alleviates oxidative stress. TIGAR induces autophagy and, thus, activates Nrf2, offering sustainable antioxidant defense in brains with extended ischemia. This previously unexplored mechanism of TIGAR may serve as a critical compensation for antioxidant activity caused by the lack of glucose in ischemic stroke.

Transparent B and Ga co-doped ZnO (BGZO)/n-ZnO/p-NiO heterojunctions were prepared on flexible polyethylene terephthalate (PET) substrates by RF magnetron sputtering at room temperature. The heterojunction shows high transmittance above 75% in the visible region, high flexibility and a good rectifying behavior. Compared with the heterojunction without BGZO layer, the performance of the device with BGZO layer is significantly improved. The turn-on voltage and the ideality factor of the heterojunction with BGZO layer is 1.2 and 2.3, respectively. The n-BGZO/n-ZnO/p-NiO heterojunction ultraviolet (UV) detectors show high UV sensitivity and fast time response.

(111)-oriented poly-crystalline diamond films (PCDs) have been deposited on Si substrates by MPCVD technology. The new electrode structure of reduced graphene oxide (RGO)/Au was successfully fabricated onto PCDs. Using the circular transmission line model (CTLM), the contact resistance of 6.6 Ω cm−2 was obtained for RGO/Au electrode on PCD surface, which was notably lower than that of 97.4 Ω cm−2 for Ti/Pt/Au electrode. Furthermore, two detectors with these two type electrodes were made respectively. The dark current, photocurrent and energy resolution of these two detectors under 5.5 MeV α particles irradiation from a 241Am source were observed. The results demonstrated that the fabrication of RGO/Au electrode onto PCD can realize a fine ohmic contact. The photocurrent of 58.7 nA for the detector with RGO/Au electrode had higher values than that of 8.8 nA for the detector with Ti/Pt/Au electrode at the bias voltage of 100 V respectively. Due to the realization of good contact on PCD surface with RGO/Au electrode, the energy resolution of 11.9% for the detector with RGO/Au electrode better than that of 24% for the detector with Ti/Pt/Au electrode can be obtained. Fabrication of the RGO/Au electrode on PCD may provide a feasible way to improve its detection performance under α particles irradiation.

High quality CdZnTe thick films were prepared on boron and gallium co-doped ZnO (BGZO) transparent conductive films by using close-spaced sublimation (CSS) method. Due to its high stability, hardness and similar thermal expansion coefficient with CdZnTe, BGZO films were also used to replace the traditional metal to form good ohmic contact with CdZnTe. CdZnTe thick film radiation detectors with BGZO/CdZnTe/BGZO structure were fabricated. The results showed a well response of the CdZnTe thick film detector (the energy resolution is about 25%) from a 60 KeV 241Am γ-source.

Circulating tumour DNAs (ctDNAs) have been reported to be associated with real-time information of progression; however, an accurate and sensitive method has not been established. Herein, a novel dual-signal amplification strategy based on a pump-free surface-enhanced Raman scattering (SERS) microfluidic chip and a catalytic hairpin assembly (CHA) technique was developed for the dynamic monitoring of BRAF V600E and KRAS G12V, which are two non-small cell lung cancer (NSCLC)-related ctDNAs. In the presence of targets, CHA reactions can be triggered between two hairpin DNAs, fixing Pd-Au core-shell nanorods (Pd-AuNRs) onto the magnetic beads (MBs) surface. Thereafter, the composite structures can assemble under the action of magnet, enabling dual-amplification of SERS signal. Using this strategy, the limit of detection (LOD) was low (i.e. at the aM level) in serum. Furthermore, the entire chip-based analysis process could be completed within 5 min, eliminating manual incubation and heavy-duty injection pumps. The selectivity, reproducibility and uniformity of the proposed pump-free SERS microfluidic chip were satisfactory. This superior analysis strategy was finally applied to quantify BRAF V600E and KRAS G12V in tumour-bearing nude mice serum, the results of which corresponded with those of real-time polymerase chain reaction. Overall, this study provides a promising alternative tool for the dynamic monitoring of ctDNA expression level which can benefit the clinical diagnosis of NSCLC.

Suicide is one of the leading causes of death and represents a significant public health problem worldwide; however, the underlying mechanism of suicide remains unclear, and there is no animal model with suicide-implicated endophenotypes for investigating the etiology, course and potential treatment targets of suicide. Thus, we generated a diathesis-stress rat model to simulate suicide-implicated endophenotypes. First, two hundred rats were screened in two rounds of learned helplessness (LH) tests and selected as learned helplessness-sensitive (LHS) rats (n = 37) and learned helplessness-resistant (LHR) rats (n = 39). Then, all LHS rats and half of the rats (randomly selected) in the LHR group were exposed to four weeks of social defeat stress (SDS) (LHS + SDS group, n = 37 and LHR + SDS group, n = 20, respectively). The remainder of the LHR rats were handled as controls (LHR + CON group, n = 19). The LHS + SDS group showed significantly more suicide-implicated endophenotypes than the LHR + CON group, including longer immobile times in the forced swim test (hopelessness), higher scores in the irritability test (irritability), shorter latencies to attack (impulsivity), longer total attack times in the resident-intruder test (aggression), and lower sucrose preference indices (anhedonia). Proteomic analyses revealed that the canonical pathways that were the most common between the LHS + SDS and LHR + CON groups were the PKA and GABA receptor pathways in the prefrontal cortex. A diathesis-stress paradigm would be a useful way to establish a rat model with suicide-implicated endophenotypes, providing novel perspectives for revealing the potential mechanism of suicide.