Mammalian Near-Infrared Image Vision through Injectable and Self-Powered Retinal Nanoantennae.

Mammals cannot see light over 700 nm in wavelength. This limitation is due to the physical thermodynamic properties of the photon-detecting opsins. However, the detection of naturally invisible near-infrared (NIR) light is a desirable ability. To break this limitation, we developed ocular injectable photoreceptor-binding upconversion nanoparticles (pbUCNPs). These nanoparticles anchored on retinal photoreceptors as miniature NIR light transducers to create NIR light image vision with negligible side effects. Based on single-photoreceptor recordings, electroretinograms, cortical recordings, and visual behavioral tests, we demonstrated that mice with these nanoantennae could not only perceive NIR light, but also see NIR light patterns. Excitingly, the injected mice were also able to differentiate sophisticated NIR shape patterns. Moreover, the NIR light pattern vision was ambient-daylight compatible and existed in parallel with native daylight vision. This new method will provide unmatched opportunities for a wide variety of emerging bio-integrated nanodevice designs and applications. VIDEO ABSTRACT.

Chromatin conformational changes at human satellite II contribute to the senescence phenotype in the tumor microenvironment.

Cellular senescence and senescence-associated secretory phenotype (SASP) in stromal cells within the tumor microenvironment promote cancer progression. Although cellular senescence has been shown to induce changes in the higher-order chromatin structure and abnormal transcription of repetitive elements in the genome, the functional significance of these changes is unclear. In this study, we examined the human satellite II (hSATII) loci in the pericentromere to understand these changes and their functional significance. Our results indicated that the hSATII loci decompact during senescence induction, resulting in new DNA-DNA interactions in distinct genomic regions, which we refer to as DRISR (Distinctive Regions Interacted with Satellite II in Replicative senescent Fibroblasts). Interestingly, decompaction occurs before the expression of hSATII RNA. The DRISR with altered chromatin accessibility was enriched for motifs associated with cellular senescence and inflammatory SASP genes. Moreover, DNA-fluorescence in situ hybridization analysis of the breast cancer tissues revealed hSATII decompaction in cancer and stromal cells. Furthermore, we reanalyzed the single-cell assay for transposase-accessible chromatin with sequencing data and found increased SASP-related gene expression in fibroblasts exhibiting hSATII decompaction in breast cancer tissues. These findings suggest that changes in the higher-order chromatin structure of the pericentromeric repetitive sequences during cellular senescence might directly contribute to the cellular senescence phenotype and cancer progression via inflammatory gene expression.

Directed evolution of adeno-associated virus for efficient gene delivery to microglia.

As the resident immune cells in the central nervous system (CNS), microglia orchestrate immune responses and dynamically sculpt neural circuits in the CNS. Microglial dysfunction and mutations of microglia-specific genes have been implicated in many diseases of the CNS. Developing effective and safe vehicles for transgene delivery into microglia will facilitate the studies of microglia biology and microglia-associated disease mechanisms. Here, we report the discovery of adeno-associated virus (AAV) variants that mediate efficient in vitro and in vivo microglial transduction via directed evolution of the AAV capsid protein. These AAV-cMG and AAV-MG variants are capable of delivering various genetic payloads into microglia with high efficiency, and enable sufficient transgene expression to support fluorescent labeling, Ca2+ and neurotransmitter imaging and genome editing in microglia in vivo. Furthermore, single-cell RNA sequencing shows that the AAV-MG variants mediate in vivo transgene delivery without inducing microglia immune activation. These AAV variants should facilitate the use of various genetically encoded sensors and effectors in the study of microglia-related biology.

Role of oxidative phosphorylation in the antidepressant effects of arketamine via the vagus nerve-dependent spleen-brain axis.

Arketamine, the (R)-enantiomer of ketamine, exhibits antidepressant-like effects in mice, though the precise molecular mechanisms remain elusive. It has been shown to reduce splenomegaly and depression-like behaviors in the chronic social defeat stress (CSDS) model of depression. This study investigated whether the spleen contributes to the antidepressant-like effects of arketamine in the CSDS model. We found that splenectomy significantly inhibited arketamine's antidepressant-like effects in CSDS-susceptible mice. RNA-sequencing analysis identified the oxidative phosphorylation (OXPHOS) pathway in the prefrontal cortex (PFC) as a key mediator of splenectomy's impact on arketamine's effects. Furthermore, oligomycin A, an inhibitor of the OXPHOS pathway, reversed the suppressive effects of splenectomy on arketamine's antidepressant-like effects. Specific genes within the OXPHOS pathways, such as COX11, UQCR11 and ATP5e, may contribute to these inhibitory effects. Notably, transforming growth factor (TGF)-ß1, along with COX11, appears to modulate the suppressive effects of splenectomy and contribute to arketamine's antidepressant-like effects. Additionally, SRI-01138, an agonist of the TGF-ß1 receptor, alleviated the inhibitory effects of splenectomy on arketamine's antidepressant-like effects. Subdiaphragmatic vagotomy also counteracted the inhibitory effects of splenectomy on arketamine's antidepressant-like effects in CSDS-susceptible mice. These findings suggest that the OXPHOS pathway and TGF-ß1 in the PFC play significant roles in the antidepressant-like effects of arketamine, mediated through the spleen-brain axis via the vagus nerve.

The effects of methylphenidate and atomoxetine on Drosophila brain at single-cell resolution and potential drug repurposing for ADHD treatment.

The stimulant methylphenidate (MPH) and the non-stimulant atomoxetine (ATX) are frequently used for the treatment of attention-deficit/hyperactivity disorder (ADHD); however, the function of these drugs in different types of brain cells and their effects on related genes remain largely unknown. To address these questions, we built a pipeline for the simultaneous examination of the activity behavior and transcriptional responses of Drosophila melanogaster at single-cell resolution following drug treatment. We selected the Drosophila with significantly increased locomotor activities (hyperactivity-like behavior) following the administration of each drug in comparison with the control (same food as the drug-treated groups with 5% sucrose, yeast, and blue food dye solution) using EasyFlyTracker. Subsequently, single cell RNA sequencing (scRNASEQ) was used to capture the transcriptome of 82,917 cells, unsupervised clustering analysis of which yielded 28 primary cell clusters representing the major cell types in adult Drosophila brain. Indeed, both neuronal and glial cells responded to MPH and ATX. Further analysis of differentially expressed genes (DEGs) revealed distinct transcriptional changes associated with these two drugs, such as two well-studied dopamine receptor genes (Dop2R and DopEcR) were responsive to MPH but not to ATX at their optimal doses, in addition to genes involved in dopamine metabolism pathways such as Syt1, Sytalpha, Syt7, and Ih in different cell types. More importantly, MPH also suppressed the expression of genes encoding other neurotransmitter receptors and synaptic signaling molecules in many cell types, especially those for Glu and GABA, while the responsive effects of ATX were much weaker. In addition to monoaminergic neuronal transmitters, other neurotransmitters have also shown a similar pattern with respect to a stronger effect associated with MPH than with ATX. Moreover, we identified four distinct glial cell subtypes responsive to the two drugs and detected a greater number of differentially expressed genes associated with ensheathing and astrocyte-like glia. Furthermore, our study provides a rich resource of candidate target genes, supported by drug set enrichment analysis (P = 2.10E-4; hypergeometric test), for the further exploration of drug repurposing. The whole list of candidates can be found at ADHDrug ( http://adhdrug.cibr.ac.cn/ ). In conclusion, we propose a fast and cost-efficient pipeline to explore the underlying molecular mechanisms of ADHD drug treatment in Drosophila brain at single-cell resolution, which may further facilitate drug repurposing applications.

[Mechanism of Shenling Baizhu Powder on treatment of alcoholic liver disease by regulating TLR4/NLRP3 pathway].

This study aims to investigate the regulatory effects of Shenling Baizhu Powder(SBP) on cellular autophagy in alcoholic liver disease(ALD) and its intervention effect through the TLR4/NLRP3 pathway. A rat model of chronic ALD was established by gavage of spirits. An ALD cell model was established by stimulating BRL3A cells with alcohol. High-performance liquid chromatography(HPLC) was utilized for the compositional analysis of SBP. Liver tissue from ALD rats underwent hematoxylin-eosin(HE) and oil red O staining for pathological evaluation. Enzyme-linked immunosorbent assay(ELISA) was applied to quantify lipopolysaccharides(LPS), tumor necrosis factor-alpha(TNF-α), interleukin-1 beta(IL-1ß), and interleukin-18(IL-18) levels. Quantitative reverse transcription polymerase chain reaction(qRT-PCR) was conducted to evaluate the mRNA expression of myeloid differentiation factor 88(MyD88) and Toll-like receptor 4(TLR4). The effect of different drugs on BRL3A cell proliferation activity was assessed through CCK-8 analysis. Western blot analysis was performed to examine the protein expression of NOD-like receptor pyrin domain-containing 3(NLRP3), nuclear factor-kappa B P65(NF-κB P65), phosphorylated nuclear factor-kappa B P65(p-P65), caspase-1, P62, Beclin1, and microtubule-associated protein 1 light chain 3(LC3Ⅱ). The results showed that SBP effectively ameliorated hepatic lipid accumulation, reduced liver function, mitigated hepatic tissue inflammation, and reduced levels of LPS, TNF-α, IL-1ß, and IL-18. Moreover, SBP exhibited the capacity to modulate hepatic autophagy induced by prolonged alcohol intake through the TLR4/NLRP3 signaling pathway. This modulation resulted in decreased expression of LC3Ⅱ and Beclin1, an elevation in P62 expression, and the promotion of autolysosome formation. These research findings imply that SBP can substantially enhance liver function and mitigate lipid irregularities in the context of chronic ALD. It achieves this by regulating excessive autophagic responses caused by prolonged spirit consumption, primarily through the inhibition of the TLR4/NLRP3 pathway.

Transcription factor GATA4 drives RNA polymerase III-directed transcription and transformed cell proliferation through a filamin A/GATA4/SP1 pathway.

RNA polymerase III (pol III) products play fundamental roles in a variety of cellular processes, including protein synthesis and cancer cell proliferation. In addition, dysregulation of pol III-directed transcription closely correlates with tumorigenesis. It is therefore of interest to identify novel pathways or factors governing pol III-directed transcription. Here, we show that transcription factor (TF) GATA binding protein 4 (GATA4) expression in SaOS2 cells was stimulated by the silencing of filamin A (FLNA), a repressor of pol III-directed transcription, suggesting that GATA4 is potentially associated with the regulation of pol III-directed transcription. Indeed, we show that GATA4 expression positively correlates with pol III-mediated transcription and tumor cell proliferation. Mechanistically, we found that GATA4 depletion inhibits the occupancies of the pol III transcription machinery factors at the loci of pol III target genes by reducing expression of both TFIIIB subunit TFIIB-related factor 1 and TFIIIC subunit general transcription factor 3C subunit 2 (GTF3C2). GATA4 has been shown to activate specificity factor 1 (Sp1) gene transcription by binding to the Sp1 gene promoter, and Sp1 has been confirmed to activate pol III gene transcription by directly binding to both Brf1 and Gtf3c2 gene promoters. Thus, the findings from this study suggest that GATA4 links FLNA and Sp1 signaling to form an FLNA/GATA4/Sp1 axis to modulate pol III-directed transcription and transformed cell proliferation. Taken together, these results provide novel insights into the regulatory mechanism of pol III-directed transcription.

Different stimuli induce endothelial dysfunction and promote atherosclerosis through the Piezo1/YAP signaling axis.

Vascular endothelial dysfunction is the initial step in atherosclerosis (AS). AS tends to occur at vascular bifurcations and curves, and endothelial cells(ECs) are highly susceptible to injury due to mechanical forces induced by disturbed flow (DF) with inconsistent blood flow directions. However, the pathogenesis of endothelial cell dysfunction in AS remains unclear and needs further study. Here, we found that Piezo1 expression was significantly increased in DF- and oxidized low-density lipoprotein(ox-LDL)-treated HUVECs in vitro and a model of atherosclerotic plaque growth in ApoE-/- mice fed a Western diet. Furthermore, Piezo1 upregulated autophagy levels in the HUVECs model, which was reversed by Piezo1 knockdown with a lentivirus-mediated shRNA system. Mechanistically, the level of Yes-associated protein (YAP), a transcriptional coactivator in the Hippo pathway, was significantly elevated in the DF- and ox-LDL-induced HUVECs model, and this effect was further inhibited by Piezo1 knockdown. Moreover, the Piezo1 agonist Yoda1 inhibited the protein level of microtubule-associated protein 1 light chain 3-II(LC3-II) and increased the protein level of sequestosome1(p62/SQSTM1) in a dose-dependent manner, while significantly promoting the protein expression and nuclear translocation of YAP. The YAP inhibitor CA3 weakened Yoda1-mediated inhibition of autophagy. Our results suggest that Piezo1 may regulate endothelial autophagy by promoting YAP activation and nuclear translocation, thereby contributing to vascular endothelial dysfunction.

Biallelic mutations of TTC12 and TTC21B were identified in Chinese patients with multisystem ciliopathy syndromes.

BACKGROUND: Abnormalities in cilia ultrastructure and function lead to a range of human phenotypes termed ciliopathies. Many tetratricopeptide repeat domain (TTC) family members have been reported to play critical roles in cilium organization and function. RESULTS: Here, we describe five unrelated family trios with multisystem ciliopathy syndromes, including situs abnormality, complex congenital heart disease, nephronophthisis or neonatal cholestasis. Through whole-exome sequencing and Sanger sequencing confirmation, we identified compound heterozygous mutations of TTC12 and TTC21B in six affected individuals of Chinese origin. These nonsynonymous mutations affected highly conserved residues and were consistently predicted to be pathogenic. Furthermore, ex vivo cDNA amplification demonstrated that homozygous c.1464 + 2 T > C of TTC12 would cause a whole exon 16 skipping. Both mRNA and protein levels of TTC12 were significantly downregulated in the cells derived from the patient carrying TTC12 mutation c.1464 + 2 T > C by real-time qPCR and immunofluorescence assays when compared with two healthy controls. Transmission electron microscopy analysis further identified ultrastructural defects of the inner dynein arms in this patient. Finally, the effect of TTC12 deficiency on cardiac LR patterning was recapitulated by employing a morpholino-mediated knockdown of ttc12 in zebrafish. CONCLUSIONS: To the best of our knowledge, this is the first study reporting the association between TTC12 variants and ciliopathies in a Chinese population. In addition to nephronophthisis and laterality defects, our findings demonstrated that TTC21B should also be considered a candidate gene for biliary ciliopathy, such as TTC26, which further expands the phenotypic spectrum of TTC21B deficiency in humans.

CO2 improves the anaerobic biodegradation intensity and selectivity of heterocyclic hydrocarbons in heavy oil.

Heterocyclic hydrocarbons pollution generated by oil spills and oilfield wastewater discharges threatens the ecological environment and human health. Here we described a strategy that combines the greenhouse gas CO2 reduction with microbial remediation. In the presence of nitrate, CO2 can improve the biodegradation efficiency of the resins and asphaltenes in heavy oil, particularly the biodegradation selectivity of the polar heterocyclic compounds by the newly isolated Klebsiella michiganensis. This strain encoded 80 genes for the xenobiotic biodegradation and metabolism, and can efficiently utilize CO2 when degrading heavy oil. The total abundance of resins and asphaltenes decreased significantly with CO2, from 40.816% to 26.909%, to 28.873% with O2, and to 36.985% with N2. The transcripts per million (TPM) value of accA gene was 57.81 under CO2 condition, while respectively 8.86 and 21.23 under O2 and N2 conditions. Under CO2 condition, the total relative percentage of N1-type heterocyclic compounds was selectively decreased from 32.25% to 22.78%, resulting in the heavy oil viscosity decreased by 46.29%. These results demonstrated a novel anaerobic degradation mechanism that CO2 can promote the anaerobic biodegradation of heterocyclic hydrocarbons in heavy oil, which provides a promising biotreatment technology for the oil-contaminated water.

Advances in treatment strategies based on scavenging reactive oxygen species of nanoparticles for atherosclerosis.

The development of atherosclerosis (AS) is closely linked to changes in the plaque microenvironment, which consists primarily of the cells that form plaque and the associated factors they secrete. The onset of inflammation, lipid deposition, and various pathological changes in cellular metabolism that accompany the plaque microenvironment will promote the development of AS. Numerous studies have shown that oxidative stress is an important condition that promotes AS. The accumulation of reactive oxygen species (ROS) is oxidative stress's most important pathological change. In turn, the effects of ROS on the plaque microenvironment are complex and varied, and these effects are ultimately reflected in the promotion or inhibition of AS. This article reviews the effects of ROS on the microenvironment of atherosclerotic plaques and their impact on disease progression over the past five years and focuses on the progress of treatment strategies based on scavenging ROS of nanoparticles for AS. Finally, we also discuss the prospects and challenges of AS treatment.

An IGF1-expressing endometrial stromal cell population is associated with human decidualization.

BACKGROUND: Decidualization refers to the process of transformation of endometrial stromal fibroblast cells into specialized decidual stromal cells that provide a nutritive and immunoprivileged matrix essential for blastocyst implantation and placental development. Deficiencies in decidualization are associated with a variety of pregnancy disorders, including female infertility, recurrent implantation failure (RIF), and miscarriages. Despite the increasing number of genes reportedly associated with endometrial receptivity and decidualization, the cellular and molecular mechanisms triggering and underlying decidualization remain largely unknown. Here, we analyze single-cell transcriptional profiles of endometrial cells during the window of implantation and decidual cells of early pregnancy, to gains insights on the process of decidualization. RESULTS: We observed a unique IGF1+ stromal cell that may initiate decidualization by single-cell RNA sequencing. We found the IL1B+ stromal cells promote gland degeneration and decidua hemostasis. We defined a subset of NK cells for accelerating decidualization and extravillous trophoblast (EVT) invasion by AREG-IGF1 and AREG-CSF1 regulatory axe. Further analysis indicates that EVT promote decidualization possibly by multiply pathways. Additionally, a systematic repository of cell-cell communication for decidualization was developed. An aberrant ratio conversion of IGF1+ stromal cells to IGF1R+ stromal cells is observed in unexplained RIF patients. CONCLUSIONS: Overall, a unique subpopulation of IGF1+ stromal cell is involved in initiating decidualization. Our observations provide deeper insights into the molecular and cellular characterizations of decidualization, and a platform for further development of evaluation of decidualization degree and treatment for decidualization disorder-related diseases.

SAR Target Recognition with Limited Training Samples in Open Set Conditions.

It is difficult to collect training samples for all types of synthetic aperture radar (SAR) targets. A realistic problem comes when unseen categories exist that are not included in training and benchmark data at the time of recognition, which is defined as open set recognition (OSR). Without the aid of side-information, generalized OSR methods used on ordinary optical images are usually not suitable for SAR images. In addition, OSR methods that require a large number of samples to participate in training are also not suitable for SAR images with the realistic situation of collection difficulty. In this regard, a task-oriented OSR method for SAR is proposed by distribution construction and relation measures to recognize targets of seen and unseen categories with limited training samples, and without any other simulation information. The method can judge category similarity to explain the unseen category. Distribution construction is realized by the graph convolutional network. The experimental results on the MSTAR dataset show that this method has a good recognition effect for the targets of both seen and unseen categories and excellent interpretation ability for unseen targets. Specifically, while recognition accuracy for seen targets remains above 95%, the recognition accuracy for unseen targets reaches 67% for the three-type classification problem, and 53% for the five-type classification problem.

Evaluation of Different Processes Impact on Flavor of Camellia Seed Oil Using HS-SPME-GC/MS.

In this study, the flavor compounds of Camellia seed oils obtained by four processes were characterized by headspace solid phase microextraction/gas chromatography/mass spectrometry (HS-SPME/GC/MS). A variety of about 76 volatile flavor compounds were identified from all the oil samples. Of the four processing processes, the pressing process can retain a lot of volatile components. Among these, compounds nonanal and 2-undecenal were predominantly in the majority of the samples. Meanwhile, other compounds such as octyl ester formic acid, octanal and 2-nonenal (E), 3-acetyldihydro 2(3H)-furanone, (E)-2-decenal, dihydro-5-penty 2(3H)-furanone, nonanoic acid, and dodecane were also among the most consistently found compounds among the oil samples analyzed. The principal component analysis carried out to categorize the data produced seven clusters of the total oil samples based on the number of flavor compounds obtained in each sample. This categorization would lead to understanding the components which highly contributed to the characteristic volatile flavor and build up the flavor profile of Camellia seed oil.

Effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery: A meta-analysis.

We performed a meta-analysis to evaluate the effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery. A systematic literature search up to June 2022 was performed and 6026 subjects with lower gastrointestinal surgery at the baseline of the studies; 3090 of them were using the wound protector, and 2936 were using no wound protector. Odds ratio (OR) with 95% confidence intervals (CIs) were calculated to assess the effect of wound protectors in reducing the incidence of surgical site wound infection in lower gastrointestinal surgery using the dichotomous methods with a random or fixed-effect model. The surgical site wound infection was significantly lower with single-ring wound protectors (OR, 0.53; 95% CI, 0.39-0.83, P = .004), and dual-ring wound protectors (OR, 0.44; 95% CI, 0.35-0.56, P < .001) in subjects with lower gastrointestinal surgery compared with no wound protector. The surgical site wound infection was significantly lower with single-ring wound protectors, and dual-ring wound protectors in subjects with lower gastrointestinal surgery compared with no wound protector. The analysis of outcomes should be with caution because of the low sample size of 5 out of 28 studies in the meta-analysis and a low number of studies in certain comparisons.

Biallelic DNAH9 mutations are identified in Chinese patients with defective left-right patterning and cilia-related complex congenital heart disease.

Defective left-right (LR) pattering results in a spectrum of laterality disorders including situs inversus totalis (SIT) and heterotaxy syndrome (Htx). Approximately, 50% of patients with primary ciliary dyskinesia (PCD) displayed SIT. Recessive variants in DNAH9 have recently been implicated in patients with situs inversus. Here, we describe six unrelated family trios and 2 sporadic patients with laterality defects and complex congenital heart disease (CHD). Through whole exome sequencing (WES), we identified compound heterozygous mutations in DNAH9 in the affected individuals of these family trios. Ex vivo cDNA amplification revealed that DNAH9 mRNA expression was significantly downregulated in these patients carrying biallelic DNAH9 mutations, which cause a premature stop codon or exon skipping. Transmission electron microscopy (TEM) analysis identified ultrastructural defects of the outer dynein arms in these affected individuals. dnah9 knockdown in zebrafish lead to the disturbance of cardiac left-right patterning without affecting ciliogenesis in Kupffer's vesicle (KV). By generating a Dnah9 knockout (KO) C57BL/6n mouse model, we found that Dnah9 loss leads to compromised cardiac function. In this study, we identified recessive DNAH9 mutations in Chinese patients with cardiac abnormalities and defective LR pattering.

Knowledge enhanced LSTM for coreference resolution on biomedical texts.

MOTIVATION: Bio-entity Coreference Resolution focuses on identifying the coreferential links in biomedical texts, which is crucial to complete bio-events' attributes and interconnect events into bio-networks. Previously, as one of the most powerful tools, deep neural network-based general domain systems are applied to the biomedical domain with domain-specific information integration. However, such methods may raise much noise due to its insufficiency of combining context and complex domain-specific information. RESULTS: In this article, we explore how to leverage the external knowledge base in a fine-grained way to better resolve coreference by introducing a knowledge-enhanced Long Short Term Memory network (LSTM), which is more flexible to encode the knowledge information inside the LSTM. Moreover, we further propose a knowledge attention module to extract informative knowledge effectively based on contexts. The experimental results on the BioNLP and CRAFT datasets achieve state-of-the-art performance, with a gain of 7.5 F1 on BioNLP and 10.6 F1 on CRAFT. Additional experiments also demonstrate superior performance on the cross-sentence coreferences. AVAILABILITY AND IMPLEMENTATION: The source code will be made available at https://github.com/zxy951005/KB-CR upon publication. Data is avaliable at http://2011.bionlp-st.org/ and https://github.com/UCDenver-ccp/CRAFT/releases/tag/v3.1.3. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

TA-MSCs, TA-MSCs-EVs, MIF: their crosstalk in immunosuppressive tumor microenvironment.

As an important component of the immunosuppressive tumor microenvironment (TME), it has been established that mesenchymal stem cells (MSCs) promote the progression of tumor cells. MSCs can directly promote the proliferation, migration, and invasion of tumor cells via cytokines and chemokines, as well as promote tumor progression by regulating the functions of anti-tumor immune and immunosuppressive cells. MSCs-derived extracellular vesicles (MSCs-EVs) contain part of the plasma membrane and signaling factors from MSCs; therefore, they display similar effects on tumors in the immunosuppressive TME. The tumor-promoting role of macrophage migration inhibitory factor (MIF) in the immunosuppressive TME has also been revealed. Interestingly, MIF exerts similar effects to those of MSCs in the immunosuppressive TME. In this review, we summarized the main effects and related mechanisms of tumor-associated MSCs (TA-MSCs), TA-MSCs-EVs, and MIF on tumors, and described their relationships. On this basis, we hypothesized that TA-MSCs-EVs, the MIF axis, and TA-MSCs form a positive feedback loop with tumor cells, influencing the occurrence and development of tumors. The functions of these three factors in the TME may undergo dynamic changes with tumor growth and continuously affect tumor development. This provides a new idea for the targeted treatment of tumors with EVs carrying MIF inhibitors.

Significantly Enhanced Photocatalytic Performance of the g-C3N4/Sulfur-Vacancy-Containing Zn3In2S6 Heterostructure for Photocatalytic H2 and H2O2 Generation by Coupling Defects with Heterojunction Engineering.

Light-driven splitting of water to produce H2 and reduction of molecular oxygen to synthesize H2O2 from water are the emerging environmentally friendly methods for converting solar energy into green energy and chemicals. In this paper, vacancy defect and heterojunction engineering effectively adjusted the conduction band position of Zn3In2S6, enriched the electron density, broadened the optical absorption range, increased the specific surface area, and accelerated the charge carrier transfer and separation of g-C3N4/sulfur-vacancy-containing Zn3In2S6 (CN/Vs-ZIS) heterostructures. As a result, all of the CN/Vs-ZIS heterostructures possessed greatly enhanced photocatalytic activities and the optimized sample 2CN/Vs-ZIS exhibited the highest visible-light photocatalytic performance. The rate of generation of H2 of 2CN/Vs-ZIS under visible light (λ > 420 nm) was 6.55 mmol g-1 h-1, which was 1.76 and 6.06 times higher than those of Vs-Zn3In2S6 and g-C3N4, respectively, and the apparent quantum yield (AQY) was 18.6% at 420 nm. Meanwhile, the 2 h yield of H2O2 of 2CN/Vs-ZIS was 792.02 µM, ∼4.72 and ∼6.04 times higher than those of pure Vs-Zn3In2S6 and g-C3N4, respectively. The enhanced reaction mechanisms for the production of photocatalytic H2 and H2O2 were also investigated. This work undoubtedly demonstrates that the synergistic effects of defect and heterojunction engineering will be the great promise for improving the photocatalytic efficiency of Zn3In2S6-based materials.

Semaphorin 3D inhibits proliferation and migration of papillary thyroid carcinoma by regulating MAPK/ERK signaling pathway.

BACKGROUND: Semaphorin 3D (SEMA3D) plays an important role in the occurrence and development of multifarious cancers. However, the relationship between SEMA3D and papillary thyroid carcinoma (PTC) remains unclear. This study aimed to investigate the functions and mechanism of SEMA3D in papillary thyroid carcinoma (PTC). METHODS: The expression of SEMA3D in PTC tissues and cell lines was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). Western blotting and immunohistochemistry (IHC) were used to detect the expression of the related proteins. CCK-8 and colony formation assays and Transwell assays were used to evaluate cell proliferation and migration, respectively. A xenograft model was induced to further verify the effect of SEMA3D in vivo. RESULTS: In this study, we found that SEMA3D was downregulated in PTC tissues and PTC cell lines (TPC-1 and BCPAP). The expression level of SEMA3D was significantly related to age (P < 0.01), extrathyroidal extension (P < 0.01), TNM stage (P < 0.01) and lymph node metastasis (P < 0.01). In vitro experiments showed that overexpression of SEMA3D inhibited the proliferation and migration of TPC-1 and BCPAP cells and that upregulated SEMA3D inhibited the phosphorylation of ERK and the expression of the phenotype-related proteins PCNA and MMP2. In addition, SEMA3D overexpression inhibited tumour growth in vivo. CONCLUSION: In this study, we found that SEMA3D is significantly downregulated in PTC tissues. SEMA3D inhibits the proliferation and migration of PTC cells and suppresses tumour growth in vivo, possibly partially through the MAPK/ERK signalling pathway, suggesting that SEMA3D may be a reliable molecular marker for the diagnosis and treatment of PTC.