COX-2/PTGS2-targeted herbal-derived oligonucleotide drug HQi-sRNA-2 was effective in spontaneous mouse lung cancer model.

In 2020, the number of deaths caused by lung cancer worldwide reached 1,796,144, making it the leading cause of cancer-related deaths. Cyclooxygenase-2/prostaglandin endoperoxide synthase 2 (COX-2/PTGS2) is overexpressed in lung cancer, which promotes tumor proliferation, invasion, angiogenesis, and resistance to apoptosis. Here, we report that the oligonucleotide drug HQi-sRNA-2 from Traditional Chinese Medicine Huangqin targeting COX-2/PTGS2 significantly inhibited proliferation, migration, and invasion and induced apoptosis in the human lung cancer cell line NCI-H460. Oral delivery of HQi-sRNA-2 bencaosomes prolonged survival, reduced tumor burden, and maintained weight in a spontaneous mouse lung cancer model. Compared with paclitaxel, HQi-sRNA-2 may be less toxic and have approximately equal efficacy in reducing tumor burden. Our previous studies reported that herbal small RNAs (sRNAs) are functional medical components. Our data suggest that sphingosine (d18:1)-HQi-sRNA-2 bencaosomes, targeting COX-2/PTGS2 and downregulating the PI3K and AKT signaling pathways, may provide novel therapeutics for lung cancer.

Oral administration of herbal oligonucleotide drug JGL-sRNA-h7 ameliorates hyperglycemia in db/db mice and beagle dogs.

Type 2 diabetes mellitus is a prevalent metabolic disease, posing a considerable threat to public health. Oligonucleotide drugs have proven to be a promising field of therapy for the diseases. In this study, we reported that a herbal small RNA (sRNA), JGL-sRNA-h7 (B34735529, F1439.L002444.A11), could exhibit potent hypoglycemic effects by targeting glucose-6-phosphatase. Oral administration of sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes ameliorated hyperglycemia and diabetic kidney injury better than metformin in db/db mice. Furthermore, glucose tolerance was also improved in sphingosine (d18:1)-JGL-sRNA-h7 bencaosomes-treated beagle dogs. Our study indicates that JGL-sRNA-h7 could be a promising hypoglycemic oligonucleotide drug.

Inverted Wide-Bandgap 2D/3D Perovskite Solar Cells with >22% Efficiency and Low Voltage Loss.

Wide-bandgap perovskites play a key role in high-performance tandem solar cells, which have the potential to break the Schockley-Queisser limit. Here, a 2D/3D hybrid wide-bandgap perovskite was developed using octane-1,8-diaminium (ODA) as spacer. The incorporation of the ODA spacer can not only significantly reduce charge carrier nonradiative recombination loss but also inhibit phase separation. Moreover, with a synergy effect using butylammonium iodide (BAI) as a surface defect passivator, both the phase stability and device performance were further improved. Compared to the control inverted device with a VOC of 1.16 V and a PCE of 18.50%, the optimized PSCs based on a surface processed 2D/3D perovskite exhibit a superior high VOC of 1.26 V and a champion PCE of 22.19%, which is a record efficiency for wide-bandgap PSCs (Eg > 1.65 eV). This work provides a very effective strategy to suppress phase separation in wide-bandgap perovskites for highly efficient and stable solar cells.

Comprehensive Characterization of Triterpene Saponins in Rhizoma Panacis Japonici by Offline Two-Dimensional Liquid Chromatography Coupled to Quadrupole Time-of-Flight Mass Spectrometry.

Rhizoma Panacis Japonici (RPJ) is an ancient herbal medicine from China that has long been employed for its medicinal benefits in relieving arthritis physical debility and diverse afflictions. The primary bioactive constituents found in RPJ are triterpene saponins, which exhibit numerous pharmacological actions, including anti-inflammatory, antioxidant, and immunomodulating effects. The present study established a straightforward and effective approach for characterizing triterpene saponins in RPJ. An offline HILIC × RP LC/QTOF-MS method was developed, along with a self-constructed in-house database containing 612 saponins reported in the Panax genus and 228 predicted metabolites. The approach achieved good chromatographic performance in isolating triterpene saponins of RPJ, with the HILIC column as the first dimension (1D) and the BEH C18 column as the second dimension (2D). The developed two-dimensional liquid chromatography system exhibited an orthogonality of 0.61 and a peak capacity of 1249. Detection was performed using a QTOF mass spectrometer in a data-independent manner (MSE) in a negative ion mode. Using the in-house database, the collected MS data were processed by an automatic workflow on UNIFI 1.8.2 software, which included data correction, matching of precursor and product ions, and peak annotation. In this study, 307 saponins were characterized from RPJ and 76 saponins were identified for the first time in Panax japonicus. This research not only enhances our understanding of the chemical characteristics of RPJ but also offers a simple and efficient method for analyzing the complex composition of herbal medicine.

Effective Delivery of Paclitaxel-Loaded Ferritin via Inverso CendR Peptide for Enhanced Cancer Therapy.

The application of drug delivery systems based on ferritin nanocarrier has been developed as a potential strategy in cancer therapy. The limited permeability of ferritin remains a challenge for drug penetration into the deeper tumor tissues. CendR peptides have been reported to bear tumor-specific penetration by recognizing neuropilin (NRP-1) receptor that overexpressed on a wide range of cancer cells. Herein, we modified CendR peptide L(RGERPPR), its retro-inverso peptide D(RPPREGR), and inverso peptide D(RGERPPR) on the outer surface of human H chain ferritin by sulfhydryl-maleimide coupling reaction. Approximately 45 paclitaxel (PTX) molecules could be loaded into each ferritin inner cavity by a thermal-triggered method at a specific ionic strength. The penetration ability of three peptide-modified ferritin constructs showed that D(RGERPPR)-modified HFtn was able to be engulfed by A549 and MCF-7 tumor cells and spheroids at the highest level. Due to the dual-targeting effect of ferritin and modified peptides, the PTX-loaded nanocomposites could effectively enter the cells with high expression of TfR1 and NRP-1 receptors and enhanced the cytotoxicity against tumor cells. Remarkably, H-D(RGE)-PTX displayed a superior tumor growth suppression efficacy in A549 tumor-bearing nude mice. The inverso CendR peptide-modified HFtn nanocarrier was first generated and could provide an effective dual-targeting platform for treatment of cancers.

Multiple-Noncovalent-Interaction-Stabilized Layered Dion-Jacobson Perovskite for Efficient Solar Cells.

Two-dimensional Dion-Jacobson (DJ) perovskites have shown improved structure stability in comparison with Ruddlesden-Popper (RP) perovskites. However, the mechanism behind the improved stability is still largely unexplored. Here a multifluorinated aromatic spacer, namely, 4F-PhDMA, has been successfully developed for 2D DJ perovskites. It is found that the 2D DJ perovskite with a 4F-PhDMA spacer exhibits a high dissociation energy due to the multiple noncovalent interactions. The optimized 2D DJ device based on the 4F-PhDMA spacer (n = 4) exhibits a champion efficiency of 16.62% with much improved light and thermal stability. This efficiency is much higher than that of the control device using an unfluorinated spacer (n = 4, PCE = 10.11%) and is among the highest efficiencies in aromatic-spacer-based 2D DJ perovskite solar cells (PSCs). Our work highlights the importance of incorporating multiple noncovalent interactions in the 2D DJ perovskite by employing a multifluorinated aromatic spacer to achieve DJ PSCs with both high efficiency and high stability.

ERK-Peptide-Inhibitor-Modified Ferritin Enhanced the Therapeutic Effects of Paclitaxel in Cancer Cells and Spheroids.

Rational design of a drug delivery system with enhanced therapeutic potency is critical for efficient tumor chemotherapy. Many protein-based drug delivery platforms have been designed to deliver drugs to target sites and improve the therapeutic efficacy. In this study, paclitaxel (PTX) molecules were encapsulated within an apoferritin nanocage-based drug delivery system with the modification of an extracellular-signal-regulated kinase (ERK) peptide inhibitor at the C-terminus of ferritin (HERK). Apoferritin is an endogenous nano-sized spherical protein which has the ability to specially bind to a majority of tumor cells via interacting with transferrin receptor 1. The ERK peptide inhibitor is a peptide which can disrupt the interaction of MEK with ERK in the mitogen-activated protein kinase/ERK pathway. By combining the targeted delivery effect of ferritin and the inhibitory effect of the ERK peptide inhibitor, the newly fabricated ferritin carrier nanoparticle HERK could still be taken up by tumor cells, and it displayed higher cell cytotoxicity than the parent ferritin. After loading with PTX, HERK-PTX displayed a favorable anticancer effect in human breast cancer cells MDA-MB-231 and lung carcinoma cells A549. The remarkable inhibitory effect on MDA-MB-231 tumor spheroids was also identified. These results indicated that the constructed HERK nanocarrier is a promising multi-functional drug delivery vehicle to enhance the therapeutic effect of drugs in cancer therapy.

Thiophene-Based Two-Dimensional Dion-Jacobson Perovskite Solar Cells with over 15% Efficiency.

Two-dimensional (2D) perovskites are emerging photovoltaic materials because of their highly tunable photophysical properties and improved environmental stability in comparison with 3D perovskites. Here, a thiophene-based bulky dication spacer, namely, 2,5-thiophenedimethylammonium (ThDMA), was developed and applicated in 2D Dion-Jacobson (DJ) perovskite. High-quality 2D DJ perovskite, (ThDMA)(MA)n-1PbnI3n+1 (nominal n = 5), with improved crystallinity, preferred vertical orientation, and enlarged spatially resolved carrier lifetime could be achieved by a one-step method using a mixed solvent of DMF/DMSO (v/v, 9:1). The optimized device exhibits a high efficiency of 15.75%, which is a record for aromatic spacer-based 2D DJ perovskite solar cells (PSCs). Moreover, the unencapsulated 2D DJ perovskite devices sustained over 95% of their original efficiency after storage in N2 for 1655 h. Importantly, both the light-soaking stability and thermal stability (T = 80 °C) of the 2D DJ perovksite devices are dramatically improved in comparison with their 3D counterparts. These results indicate that highly efficient and stable 2D DJ PSCs could be achieved by developing thiophene-based aromatic spacers as well as device engineering.

Nanoformulations to Enhance the Bioavailability and Physiological Functions of Polyphenols.

Polyphenols are micronutrients that are widely present in human daily diets. Numerous studies have demonstrated their potential as antioxidants and anti-inflammatory agents, and for cancer prevention, heart protection and the treatment of neurodegenerative diseases. However, due to their vulnerability to environmental conditions and low bioavailability, their application in the food and medical fields is greatly limited. Nanoformulations, as excellent drug delivery systems, can overcome these limitations and maximize the pharmacological effects of polyphenols. In this review, we summarize the biological activities of polyphenols, together with systems for their delivery, including phospholipid complexes, lipid-based nanoparticles, protein-based nanoparticles, niosomes, polymers, micelles, emulsions and metal nanoparticles. The application of polyphenol nanoparticles in food and medicine is also discussed. Although loading into nanoparticles solves the main limitation to application of polyphenolic compounds, there are some concerns about their toxicological safety after entry into the human body. It is therefore necessary to conduct toxicity studies and residue analysis on the carrier.

Enhanced Reactive Oxygen Species Levels by an Active Benzothiazole Complex-Mediated Fenton Reaction for Highly Effective Antitumor Therapy.

Breaking the threshold of intracellular reactive oxygen species (ROS) levels can cause nonspecific oxidative damage to proteins and lead to the Fenton reaction-mediated exogenous ROS production to be a new promising anticancer strategy. However, the problems, including the inefficient transport of metal catalysts and insufficient endogenous hydrogen peroxide (H2O2) content in cells, still need to be improved. In this study, a functional nanosystem encapsulated with benzothiazole complexes (FeTB2) and the photosensitizer indocyanine green (ICG) was designed for highly effective antitumor therapy. The surface of the nanocarriers was modified with dihydroartemisinin (DHA)-grafted polyglutamic acid. The induced hyperthermia enables the lipid-polymer shell to depolymerize, releasing FeTB2. The released FeTB2 could kill tumor cells in two different ways by inhibiting DNA replication and catalyzing H2O2 to produce active •OH. Moreover, the conjugated DHA could increase the amount of peroxides in tumor cells and significantly enhance the ROS yield. This work has provided solid evidence that the present nanosystem enables a significant effect on tumor killing through the combined inhibition of DNA replication and ROS-mediated oxidative damage by regulation of the tumor microenvironment, providing a ROS-mediated high-efficiency antitumor strategy.

Application of Plant Viruses as a Biotemplate for Nanomaterial Fabrication.

Viruses are widely used to fabricate nanomaterials in the field of nanotechnology. Plant viruses are of great interest to the nanotechnology field because of their symmetry, polyvalency, homogeneous size distribution, and ability to self-assemble. This homogeneity can be used to obtain the high uniformity of the templated material and its related properties. In this paper, the variety of nanomaterials generated in rod-like and spherical plant viruses is highlighted for the cowpea chlorotic mottle virus (CCMV), cowpea mosaic virus (CPMV), brome mosaic virus (BMV), and tobacco mosaic virus (TMV). Their recent studies on developing nanomaterials in a wide range of applications from biomedicine and catalysts to biosensors are reviewed.

PDGFß receptor-targeted delivery of truncated transforming growth factor ß receptor type II for improving the in vitro and in vivo anti-renal fibrosis activity via strong inactivation of TGF-ß1/Smad signaling pathway.

Truncated transforming growth factor ß receptor type II (tTßRII), serving as a trap for binding excessive transforming growth factor ß1 (TGF-ß1) by means of competing with wild-type TßRII, is a promising strategy for the treatment of kidney fibrosis. Platelet-derived growth factor ß receptor (PDGFßR) is highly expressed in interstitial myofibroblasts in kidney fibrosis. This study identified the interaction between a novel tTßRII variant Z-tTßRII (PDGFßR-specific affibody ZPDGFßR fused to the N-terminus of tTßRII) and TGF-ß1. Moreover, Z-tTßRII highly targeted to TGF-ß1-activated NIH3T3 cells and UUO-induced fibrotic kidney, but less to normal cells, tissues, and organs. Furthermore, Z-tTßRII significantly inhibited cell proliferation and migration, and reduced fibrosis markers expression and phosphorylation level of Smad2/3 in activated NIH3T3 cells. Meanwhile, Z-tTßRII markedly alleviated the kidney histopathology and fibrotic responses, and inhibited the TGF-ß1/Smad signaling pathway in UUO mice. Besides, Z-tTßRII showed good safety performance in the treatment of UUO mice. In conclusion, these results demonstrated that Z-tTßRII may be a potential candidate for a targeting therapy on renal fibrosis due to the high potential of fibrotic kidney-targeting and strong anti-renal fibrosis activity.

Salinization of groundwater in shale gas extraction area in the Sichuan Basin, China: Implications for water protection in shale regions with well-developed faults.

The expanding growth of shale gas development has sparked global concern over water-related environmental issues. However, research on groundwater contamination in shale gas areas in China remains limited, impeding environmentally friendly industry practices. To address this gap, we investigated the Wufeng-Longmaxi shale region in the Sichuan Basin, encompassing both operational and prospective shale gas extraction sites, to assess the effects of shale gas operations on shallow groundwater quality. We found there was no significant correlation between groundwater quality and the minimum distance from the shale gas well pads, and some groundwater samples located far from shale gas well pads, rather than those close to pads, were salinized. These findings suggest minimal impacts from shale gas drilling and hydraulic fracturing. The salinized groundwater samples are characterized by high salinity levels and ion concentrations, and are located near fault zones. The primary source of shallow groundwater salinization was derived from the Triassic formation brines confirmed through the assessment of the sensitivity and conservative mixing models. Faults in the study area were identified as pathways for the upward migration of Triassic brines, evidenced by the proximity of salinized samples to fault zones. However, further investigation is required to ascertain whether shale gas extraction activities have induced the migration of formation brines. The occurrence and reactivation of faults, induced by microseismic activities, may pose an increased risk of groundwater contamination in tectonically complex fault zones during shale gas extraction. Therefore, it is imperative to enhance extraction strategies and technologies, particularly in shale regions with well-developed faults, such as optimizing well placement regulation, controlling hydraulic fracturing scale, and strengthening environmental monitoring. By shedding light on potential environmental ramifications of shale gas extraction, especially in fault-rich regions, our study informs water protection strategies and the sustainable advancement of the shale gas industry.

Bu zhong Yiqi Decoction ameliorates mild cognitive impairment by improving mitochondrial oxidative stress damage via the SIRT3/MnSOD/OGG1 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Bu-Zhong-Yi-Qi Decoction(BZYQD) is a traditional formula commonly used in China, known for its effects in tonifying Qi and raising Yang. It can relieve symptoms of cognitive impairment such as forgetfulness and lack of concentration caused by qi deficiency, which is common in aging and debilitating. However, much of the current research on BZYQD has been focused on its impact on the digestive system, leaving its molecular mechanisms in improving cognitive function largely unexplored. AIM OF THE STUDY: Cognitive decline in the aging central nervous system is intrinsically linked to oxidative damage. This study aims to investigate the therapeutic mechanism of BZYQD in treating mild cognitive impairment caused by qi deficiency, particularly through repair of mitochondrial oxidative damage. MATERIALS AND METHODS: A rat model of mild cognitive impairment (MCI) was established by administering reserpine subcutaneously for two weeks, followed by a two-week treatment with BZYQD/GBE. In vitro experiments were conducted to assess the effects of BZYQD on neuronal cells using a H2O2-induced oxidative damage model in PC12 cells. The open field test and the Morris water maze test evaluated the cognitive and learning memory abilities of the rats. HE staining and TEM were employed to observe morphological changes in the hippocampus and its mitochondria. Mitochondrial activity, ATP levels, and cellular viability were measured using assay kits. Protein expression in the SIRT3/MnSOD/OGG1 pathway was analyzed in tissues and cells through western blotting. Levels of 8-OH-dG in mitochondria extracted from tissues and cells were quantified using ELISA. Mitochondrial morphology in PC12 cells was visualized using Mito Red, and mitochondrial membrane potential was assessed using the JC-1 kit. RESULTS: BZYQD treatment significantly improved cognitive decline caused by reserpine in rats, as well as enhanced mitochondrial morphology and function in the hippocampus. Our findings indicate that BZYQD mitigates mtDNA oxidative damage in rats by modulating the SIRT3/MnSOD/OGG1 pathway. In PC12 cells, BZYQD reduced oxidative damage to mitochondria and mtDNA in H2O2-induced conditions and was associated with changes in the SIRT3/MnSOD/OGG1 pathway. CONCLUSION: BZYQD effectively counteracts reserpine-induced mild cognitive impairment and ameliorates mitochondrial oxidative stress damage through the SIRT3/MnSOD/OGG1 pathway.

Synthesis, Fluorescence, and Bioactivity of Novel Isatin Derivatives.

The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1PTP with IC50 of 11 ± 3 µM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 µM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.

LncRNA THRIL, transcriptionally activated by AP-1 and stabilized by METTL14-mediated m6A modification, accelerates LPS-evoked acute injury in alveolar epithelial cells.

Acute lung injury (ALI) and its extreme manifestation, acute respiratory distress syndrome (ARDS), are life-threatening diseases in intensive care units. LncRNA THRIL plays a crucial role in regulating the inflammatory response; however, the potential function of THRIL in ALI/ARDS and the associated mechanism remain unclear. In our study, we found that THRIL was upregulated in the serum of ALI/ARDS patients, and its increased expression was positively correlated with the inflammatory cytokines IL-17. In LPS-induced A549 cells, knockdown of THRIL inhibited the release of the proinflammatory cytokines TNF-α, IL-1ß, IL-17, and IL-6, decreased the number of monodansylcadaverine-positive cells and LC3-II with immunofluorescence staining, decreased the expression of autophagy marker ATG7 and Beclin1, and increased expression of p62. Mechanistically, the transcription factor AP-1 bound directly to the THRIL promoter region and activated its transcription by c-Jun upon LPS exposure. Moreover, m6A modification of THRIL was increased in LPS-treated A549 cells, and METTL14 knockdown significantly abolished m6A modification and reduced stabilization of THRIL mRNA. In conclusion, our findings reveal that THRIL, transcriptionally activated by AP-1 and modified by METTL14-mediated m6A modification, induces autophagy in LPS-treated A549 cells, suggesting the potential application of THRIL for ALI/ARDS therapy.

Dual-targeted delivery of paclitaxel and indocyanine green with aptamer-modified ferritin for synergetic chemo-phototherapy.

The combination of phototherapy and chemotherapy has become attractive and effective cancer treatment. However, the accurate delivery of both chemo-phototherapy drugs to the target site as well as the development of high-efficient phototherapy and chemotherapy drugs remain major challenges. In this study, indocyanine green (ICG) and paclitaxel (PTX)-loaded aptamer ferritin (HAS1411-PTX-ICG) was developed as a biocompatible nanoplatform for combined chemo/photothermal/photodynamic (PTT/PDT) therapy that was safe and highly effective against tumors. HAS1411 was prepared by coupling aptamer AS1411 to the surface of human H chain ferritin (HFtn) by the carbon diimide method to further enhance the targeting of HFtn. Both ICG and PTX were effectively encapsulated in the HAS1411 by incubation at 60 â„ƒ. Moreover, under near-infrared (NIR) light irradiation, HAS1411 enhanced the photothermal effect and cell internalization of ICG, as well as the production of reactive oxygen species in cancer cells. HAS1411-PTX-ICG displayed effective cytotoxicity and a significant tumor spheroids inhibitory effect owning to the improved internalization of PTX and ICG mediated by TfR1 and nucleolin dual receptors. Co-loaded PTX combined with ICG can produce chemo/PTT/PDT under near-infrared (NIR) light irradiation, enhancing the anti-tumor effect. The dual-targeting HAS1411 nanocarrier developed in this study can be a promising delivery system for cancer therapy and the fabricated HAS1411-PTX-ICG possesses potential application in chemo-phototherapy.

Co-Encapsulation of Hydrophilic and Hydrophobic Drugs into Human H Chain Ferritin Nanocarrier Enhances Antitumor Efficacy.

The biocompatible protein nanocarrier with homogeneous particle size is a promising candidate material for the delivery of targeted drugs to tumors. Doxorubicin (DOX) is a commonly prescribed anthracycline antitumor drug, although it may cause nephrotoxicity and cardiotoxicity. The Chinese herbal remedy ursolic acid (UA), a pentacyclic triterpenoid with anticancer action, has been used as a potential drug sensitizer to increase the effectiveness of chemotherapy and pharmacological therapy. Therefore, the dose of DOX can be reduced by compatibility with UA to lower its side effects. Ferritin binds to tumor cells through an interaction with the transferrin receptor 1 (TfR1), which is overexpressed in human cancer cells. In this study, the hydrophobic drug UA and the hydrophilic drug DOX were successfully encapsulated into the ferritin inner cavity using the thermal treatment method incubated at 60 °C for 4 h. The results demonstrated that loaded ferritin could specifically enter breast cancer cells MCF-7 and non-small-cell lung cancer cells A549 in comparison with free UA and DOX, enhancing their therapeutic effects. The loading ratio of two drugs was optimized in the constructed nanocarriers, and the effectiveness of the constructed nanodrugs in inhibiting tumor proliferation was verified by cell apoptosis and three-dimensional (3D) tumor spheroids studies. For the first time, the hydrophilic and hydrophobic drugs were loaded simultaneously within unmodified ferritin without other addition of additives, which would reduce the toxic side effects of DOX and enhance its therapeutic effect. This study also showed that the ferritin-based nanocarrier has potential for drug delivery to tumors.

Temporal-spatial risk assessment of COVID-19 under the influence of urban spatial environmental parameters: The case of Shenyang city.

Respiratory infection is the main route for the transmission of coronavirus pneumonia, and the results have shown that the urban spatial environment significantly influences the risk of infection. Based on the Wells-Riley model of respiratory infection probability, the study determined the human respiratory-related parameters and the effective influence range; extracted urban morphological parameters, assessed the ventilation effects of different spatial environments, and, combined with population flow monitoring data, constructed a method for assessing the risk of Covid-19 respiratory infection in urban-scale grid cells. In the empirical study in Shenyang city, a severe cold region, urban morphological parameters, population size, background wind speed, and individual behavior patterns were used to calculate the distribution characteristics of temporal and spatial concomitant risks in urban areas grids under different scenarios. The results showed that the correlation between the risk of respiratory infection in urban public spaces and the above variables was significant. The exposure time had the greatest degree of influence on the probability of respiratory infection risk among the variables. At the same time, the change in human body spacing beyond 1 m had a minor influence on the risk of infection. Among the urban morphological parameters, building height had the highest correlation with the risk of infection, while building density had the lowest correlation. The actual point distribution of the epidemic in Shenyang from March to April 2022 was used to verify the evaluation results. The overlap rate between medium or higher risk areas and actual cases was 78.55%. The planning strategies for epidemic prevention and control were proposed for the spatial differentiation characteristics of different risk elements. The research results can accurately classify the risk level of urban space and provide a scientific basis for the planning response of epidemic prevention and control and the safety of public activities.

M6A-mediated upregulation of HOXC10 promotes human hepatocellular carcinoma development through PTEN/AKT/mTOR signaling pathway.

Human Hox genes (Homeobox) play a crucial role in embryonic development and cancer. The HOXC10 gene, a member of the HOX family, has been reported abnormally expressed in several cancers. However, the association between HOXC10 and hepatocellular carcinoma (HCC) remains to be elucidated. In the present study, tissue microarray cohort data showed that high levels of HOXC10 expression predicted a poor survival in HCC patients. Meanwhile, HOXC10 was significantly upregulated in the Huh7 cell line compared with the well differentiated cell line HepG2 and human normal liver cells. Functionally, silencing HOXC10 in Huh7 cells inhibited cell proliferation, increased apoptosis, and inhibited invasion and migration of HCC cells. HOXC10 overexpression in HepG2 cells increased cell proliferation, decreased apoptosis, and increased invasion and migration of HCC cells. In the HepG2 xenograft models, HOXC10 increased the tumor volume and weight compared with control. Mechanistically, the m6A modification of HOXC10 by METTL3 enhanced its expression by enhancing its mRNA stability. Both the in vitro and in vivo results showed that overexpressed HOXC10 activated the PTEN/AKT/mTOR pathway. In summary, the findings highlight the importance of HOXC10 in the regulation of HCC progression. HOXC10 is potentially a future therapeutic target for HCC treatment.