Molecular classification of geriatric breast cancer displays distinct senescent subgroups of prognostic significance.

Breast cancer in the elderly presents distinct biological characteristics and clinical treatment responses compared with cancer in younger patients. Comprehensive Geriatric Assessment is recommended for evaluating treatment efficacy in elderly cancer patients based on physiological classification. However, research on molecular classification in older cancer patients remains insufficient. In this study, we identified two subgroups with distinct senescent clusters among geriatric breast cancer patients through multi-omics analysis. Using various machine learning algorithms, we developed a comprehensive scoring model called "Sene_Signature," which more accurately distinguished elderly breast cancer patients compared with existing methods and better predicted their prognosis. The Sene_Signature was correlated with tumor immune cell infiltration, as supported by single-cell transcriptomics, RNA sequencing, and pathological data. Furthermore, we observed increased drug responsiveness in patients with a high Sene_Signature to treatments targeting the epidermal growth factor receptor and cell-cycle pathways. We also established a user-friendly web platform to assist investigators in assessing Sene_Signature scores and predicting treatment responses for elderly breast cancer patients. In conclusion, we developed a novel model for evaluating prognosis and therapeutic responses, providing a potential molecular classification that assists in the pre-treatment assessment of geriatric breast cancer.

SARC-UNet: A coronary artery segmentation method based on spatial attention and residual convolution.

BACKGROUND AND OBJECTIVE: Coronary artery segmentation is a pivotal field that has received increasing attention in recent years. However, this task remains challenging because of the inhomogeneous distributions of the contrast agent and dim light, resulting in noise, vascular breakages and small vessel losses in the obtained segmentation results. METHODS: To acquire better automatic blood vessel segmentation results for coronary angiography images, a UNet-based segmentation network (SARC-UNet) is constructed for coronary artery segmentation; this approach is based on residual convolution and spatial attention. First, we use the low-light image enhancement (LIME) approach to increase the contrast and clarity levels of coronary angiography images. Then, we design two residual convolution fusion modules (RCFM1 and RCFM2) that can successfully fuse the local and global information of coronary images while also capturing the characteristics of finer-grained blood vessels, hence preventing the loss of tiny blood vessels in the segmentation findings. Finally, using a cascaded waterfall structure, we create a new location-enhanced spatial attention (LESA) mechanism that can efficiently improve the long-distance dependencies between coronary vascular pixel features, eradicating vascular ruptures and noise in the segmentation results. RESULTS: This article subjectively and objectively evaluates the experimental results. This method has performed well on five general indicators. Furthermore, it outperforms the connectivity indicators proposed in this article. This method can effectively segment blood vessels and obtain higher accuracy results. CONCLUSIONS: Numerous experiments have shown that the suggested method outperforms the state-of-the-art approaches, particularly in terms of vessel connectivity and small blood vessel segmentation.

Annexin-A1 tripeptide enhances functional recovery and mitigates brain damage in traumatic brain injury by inhibiting neuroinflammation and preventing ANXA1 nuclear translocation in mice.

This study explores the role and mechanism of Annexin-A1 Tripeptide (ANXA1sp) in mitigating neuronal damage and promoting functional recovery in a mouse model of traumatic brain injury (TBI). Our goal is to identify ANXA1sp as a potential therapeutic drug candidate for TBI treatment. Adult male C57BL/6J mice were subjected to controlled cortical impact (CCI) to simulate TBI, supplemented by an in vitro model of glutamate-induced TBI in HT22 cells.  We assessed neurological deficits using the Modified Neurological Severity Score (mNSS), tested sensorimotor functions with beam balance and rotarod tests, and evaluated cognitive performance via the Morris water maze. Neuronal damage was quantified using Nissl and TUNEL staining, while microglial activation and inflammatory responses were measured through immunostaining, quantitative PCR (qPCR), Western blotting, and ELISA. Additionally, we evaluated cell viability in response to glutamate toxicity using the Cell Counting Kit-8 (CCK-8) assay and lactate dehydrogenase (LDH) release. Intraperitoneal administration of ANXA1sp significantly enhanced neurological outcomes, markedly reducing sensorimotor and cognitive impairments caused by TBI. This treatment resulted in a significant reduction in lesion volume and decreased neuronal cell death in the ipsilateral cortex. Moreover, ANXA1sp effectively diminished microglial activation around the brain lesion and decreased the levels of pro-inflammatory markers such as IL-6, IL-1ß, TNF-α, and TGF-ß in the cortex, indicating a significant reduction in neuroinflammation post-TBI. ANXA1sp also offered protection against neuronal cell death induced by glutamate toxicity, primarily by inhibiting the nuclear translocation of ANXA1, highlighting its potential as a neuroprotective strategy in TBI management. Administration of ANXA1sp significantly reduced neuroinflammation and neuronal cell death, primarily by blocking the nuclear translocation of ANXA1. This treatment substantially reduced brain damage and improved neurological functional recovery after TBI. Consequently, ANXA1sp stands out as a promising neuroprotective agent for TBI therapy.

A novel rapid visual nucleic acid detection technique for tick-borne encephalitis virus by combining RT-recombinase-aided amplification and CRISPR/Cas13a coupled with a lateral flow dipstick.

Tick-borne encephalitis virus (TBEV), a zoonotic pathogen, can cause severe neurological complications and fatal outcomes in humans. Early diagnosis of TBEV infection is crucial for clinical practice. Although serological assays are frequently employed for detection, the lack of antibodies in the early stages of infection and the cross-reactivity of antibodies limit their efficacy. Conventional molecular diagnostic methods such as RT-qPCR can achieve early and accurate identification but require specialized instrumentation and professionals, hindering their application in resource-limited areas. Our study developed a rapid and visual TBEV molecular detection method by combining RT-recombinase-aided amplification, the CRISPR/Cas13a system, and lateral flow dipsticks. The diagnostic sensitivity of this method is 50 CFU/ml, with no cross-reactivity with a variety of viruses. The detection can be carried out within 1 h at a temperature between 37 and 42 °C, and the results can be visually determined without the need for complex instruments and professionals. Subsequently, this assay was used to analyze clinical samples from 15 patients suspected of TBEV infection and 10 healthy volunteers, and its sensitivity and specificity reached 100 %, which was consistent with the results of RT-qPCR. These results indicate that this new method can be a promising point-of-care test for the diagnosis of tick-borne encephalitis.

Establishment and application of a rapid visualization method for detecting Vibrio parahaemolyticus nucleic acid.

Background: Swift and accurate detection of Vibrio parahaemolyticus, which is a prominent causative pathogen associated with seafood contamination, is required to effectively combat foodborne disease and wound infections. The toxR gene is relatively conserved within V. parahaemolyticus and is primarily involved in the expression and regulation of virulence genes with a notable degree of specificity. The aim of this study was to develop a rapid, simple, and constant temperature detection method for V. parahaemolyticus in clinical and nonspecialized laboratory settings. Methods: In this study, specific primers and CRISPR RNA were used to target the toxR gene to construct a reaction system that combines recombinase polymerase amplification (RPA) with CRISPR‒Cas13a. The whole-genome DNA of the sample was extracted by self-prepared sodium dodecyl sulphate (SDS) nucleic acid rapid extraction reagent, and visual interpretation of the detection results was performed by lateral flow dipsticks (LFDs). Results: The specificity of the RPA-CRISPR/Cas13a-LFD method was validated using V. parahaemolyticus strain ATCC-17802 and six other non-parahaemolytic Vibrio species. The results demonstrated a specificity of 100%. Additionally, the genomic DNA of V. parahaemolyticus was serially diluted and analysed, with a minimum detectable limit of 1 copy/µL for this method, which was greater than that of the TaqMan-qPCR method (102 copies/µL). The established methods were successfully applied to detect wild-type V. parahaemolyticus, yielding results consistent with those of TaqMan-qPCR and MALDI-TOF MS mass spectrometry identification. Finally, the established RPA-CRISPR/Cas13a-LFD method was applied to whole blood specimens from mice infected with V. parahaemolyticus, and the detection rate of V. parahaemolyticus by this method was consistent with that of the conventional PCR method. Conclusions: In this study, we describe an RPA-CRISPR/Cas13a detection method that specifically targets the toxR gene and offers advantages such as simplicity, rapidity, high specificity, and visual interpretation. This method serves as a valuable tool for the prompt detection of V. parahaemolyticus in nonspecialized laboratory settings.

Durability and Mechanical Properties of Nano-SiO2 and Polyvinyl Alcohol Fiber-Reinforced Cementitious Composites Subjected to Saline Freeze-Thaw Cycles.

To investigate the effects of nano-SiO2 (NS) and polyvinyl alcohol (PVA) fibers on the durability and mechanical properties of cementitious composites subjected to saline freeze-thaw cycling, a series of PVA fiber-reinforced cementitious composite (PFRCC) specimens were prepared using various fiber contents, and a series of NS and PVA fiber-reinforced cementitious composite (NPFRCC) specimens were prepared using various combinations of NS and fiber contents. Durability and fracture toughness tests were subsequently conducted on the specimens after different numbers of saline freeze-thaw cycles. The results indicate that the degradation of material properties can be divided into slow and accelerated damage stages before/after 50 freeze-thaw cycles. The durability and fracture toughness of the specimen series tended to increase, then decrease with increasing NS and PVA contents, suggesting optimum levels. When the PVA fiber content was 0.5%, PFRCC specimens had the best durability after saline freeze-thaw cycles; when the NS and PVA fiber contents were 1.0% and 0.5%, respectively, NPFRCC specimens had the best durability and fracture properties, and the initiation toughness, destabilization toughness, and fracture energy after 100 saline freeze-thaw cycles were 120.69%, 160.02%, and 451.31%, respectively. The results of this study may guide future exploration of the durability and mechanical properties of concrete subjected to freeze-thaw action.

An 'activator-repressor' loop controls the anthocyanin biosynthesis in red-skinned pear.

The color of red-skinned pear (Pyrus spp.) is primarily attributed to accumulation of anthocyanins, which provide nutritional benefits for human health and are closely associated with the commercial value of fruits. Here, we reported the functional characterization of a R2R3-MYB repressor PyMYB107, which forms an 'activator-repressor' loop to control anthocyanin accumulation in the red-skinned pear. PyMYB107 overexpression inhibited anthocyanin biosynthesis in both pear calli and fruits, while virus-induced gene silencing of PyMYB107 increased anthocyanin accumulation in pear fruits. Furthermore, ectopic expression of PyMYB107 decreased anthocyanin accumulation in tomato, strawberry and tobacco. PyMYB107 can competitively bind to PybHLH3 with PyMYB10/MYB114, thereby suppressing the transcriptional activation of key anthocyanin biosynthesis genes, PyANS and PyUFGT. Site-directed mutagenesis showed that mutations within the R3 domain and EAR motif of PyMYB107 eliminated its repressive activity. Additionally, PyMYB107 exhibited a comparable expression pattern to PyMYB10/MYB114 and was transcriptionally activated by them. Our finding advanced comprehension of the repression mechanism underlying anthocyanin accumulation, providing valuable molecular insights into improving quality of pear fruits.

The Effects of Calcium Nitrite on the Mechanical Properties and Microstructure of Early-Age Frozen Cement Paste.

The objective of this paper is to investigate the effect of calcium nitrite (CN) on improving the mechanical properties and microstructures of early-frozen cement paste. Cement pastes containing 1%, 1.5%, 2%, 2.5%, and 3% CN were prepared. One batch of samples was frozen at -6 °C for 7 days and then cured at 20 °C, and the other batch of samples was directly cured at 20 °C as a control. The compressive strength, ultrasonic pulse velocity, and resistivity of all specimens at different target ages were measured under these two curing conditions. The hydration products and microstructures of typical samples were observed using XRD and scanning SEM. The results showed that the addition of 1.5% CN could promote cement hydration and enhance slurry densification, thereby increasing the compressive strength, ultrasonic pulse velocity, and electrical resistivity of the slurry, and positively affecting the early freezing resistance of the slurry. However, when the CN dosage exceeded 1.5%, the internal structure of the slurry was loose and porous due to the generation of a large amount of nitrite-AFm, which negatively affects the properties of the cement paste. In addition, the effectiveness of CN is only limited to temperature environments above -6 °C. Concrete antifreeze suitable for lower temperatures still requires further research.

The Effect of Fermentation on the Chemical Constituents of Gastrodia Tuber Hallimasch Powder (GTHP) Estimated by UHPLC-Q-Orbitrap HRMS and HPLC.

OBJECTIVE: To compare the effect of fermentation on the chemical constituents of Gastrodia Tuder Halimasch Powder (GTHP), to establish its fingerprinting and multicomponent content determination, and to provide a basis for the processing, handling, and clinical application of this herb. METHODS: Ultra-high-performance liquid chromatography-quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) was used to conduct a preliminary analysis of the chemical constituents in GTHP before and after fermentation. High-performance liquid chromatography (HPLC) was used to determine some major differential components of GTHP and establish fingerprints. Cluster analysis (CA), and principal component analysis (PCA) were employed for comprehensive evaluation. RESULTS: Seventy-nine compounds were identified, including flavonoids, organic acids, nucleosides, terpenoids, and others. The CA and PCA results showed that ten samples were divided into three groups. Through standard control and HPLC analysis, 10 compounds were identified from 22 peaks, namely uracil, guanosine, adenosine, 5-hydroxymethylfurfural (5-HMF), daidzin, genistin, glycitein, daidzein, genistein, and ergosterol. After fermentation, GTHP exhibited significantly higher contents of uracil, guanosine, adenosine, 5-hydroxymethylfurfural, and ergosterol and significantly lower genistein and daidzein contents. CONCLUSIONS: The UHPLC-Q-Orbitrap HRMS and HPLC methods can effectively identify a variety of chemical components before and after the fermentation of GTHP. This study provides a valuable reference for further research on the rational clinical application and quality control improvement of GTHP.

Activation of σ-1 receptor mitigates estrogen withdrawal-induced anxiety/depressive-like behavior in mice via restoration of GABA/glutamate signaling and neuroplasticity in the hippocampus.

Postpartum depression (PPD) is a significant contributor to maternal morbidity and mortality. The Sigma-1 (σ-1) receptor has received increasing attention in recent years because of its ability to link different signaling systems and exert its function in the brain through chaperone actions, especially in neuropsychiatric disorders. YL-0919, a novel σ-1 receptor agonist developed by our institute, has shown antidepressive and anxiolytic effects in a variety of animal models, but effects on PPD have not been revealed. In the present study, excitatory/inhibitory signaling in the hippocampus was reflected by GABA and glutamate and their associated excitatory-inhibitory receptor proteins, the HPA axis hormones in the hippocampus were assessed by ELISA. Finally, immunofluorescence for markers of newborn neuron were undertaken in the dentate gyri, along with dendritic spine staining and dendritic arborization tracing. YL-0919 rapidly improves anxiety and depressive-like behavior in PPD-like mice within one week, along with normalizing the excitation/inhibition signaling as well as the HPA axis activity. YL-0919 rescued the decrease in hippocampal dendritic complexity and spine density induced by estrogen withdrawal. The study results suggest that YL-0919 elicits a therapeutic effect on PPD-like mice; therefore, the σ-1 receptor may be a novel promising target for PPD treatment in the future.

A review of methods for assessment of cognitive function in high-altitude hypoxic environments.

Hypoxic environments like those present at high altitudes may negatively affect brain function. Varying levels of hypoxia, whether acute or chronic, are previously shown to impair cognitive function in humans. Assessment and prevention of such cognitive impairment require detection of cognitive changes and impairment using specific cognitive function assessment tools. This paper summarizes the findings of previous research, outlines the methods for cognitive function assessment used at a high altitude, elaborates the need to develop standardized and systematic cognitive function assessment tools for high-altitude hypoxia environments.

Intermittent hypoxia training effectively protects against cognitive decline caused by acute hypoxia exposure.

Intermittent hypoxia training (IHT) is a promising approach that has been used to induce acclimatization to hypoxia and subsequently lower the risk of developing acute mountain sickness (AMS). However, the effects of IHT on cognitive and cerebrovascular function after acute hypoxia exposure have not been characterized. In the present study, we first confirmed that the simplified IHT paradigm was effective at relieving AMS at 4300 m. Second, we found that IHT improved participants' cognitive and neural alterations when they were exposed to hypoxia. Specifically, impaired working memory performance, decreased conflict control function, impaired cognitive control, and aggravated mental fatigue induced by acute hypoxia exposure were significantly alleviated in the IHT group. Furthermore, a reversal of brain swelling induced by acute hypoxia exposure was visualized in the IHT group using magnetic resonance imaging. An increase in cerebral blood flow (CBF) was observed in multiple brain regions of the IHT group after hypoxia exposure as compared with the control group. Based on these findings, the simplified IHT paradigm might facilitate hypoxia acclimatization, alleviate AMS symptoms, and increase CBF in multiple brain regions, thus ameliorating brain swelling and cognitive dysfunction.

Atmospheric HONO emissions in China: Unraveling the spatiotemporal patterns and their key influencing factors.

Nitrous acid (HONO) can be photolyzed to produce hydroxyl radicals (OH) in the atmosphere. OH plays a critical role in the formation of secondary pollutants like ozone (O3) and secondary organic aerosols (SOA) via various oxidation reactions. Despite the abundance of recent HONO studies, research on national HONO emissions in China remains relatively limited. Therefore, this study employed a "wetting-drying" model and bottom-up approach to develop a high-resolution gridded inventory of HONO emissions for mainland China using multiple data. We used the Monte Carlo method to estimate the uncertainty in HONO emissions. In addition, the primary sources of HONO emissions were identified and their spatiotemporal distribution and main influencing factors were studied. The results indicated that the total HONO emissions in mainland China in 2016 were 0.77 Tg N (R50: 0.28-1.42 Tg N), with soil (0.42 Tg N) and fertilization (0.26 Tg N) as the primary sources, jointly contributing to over 87% of the total. Notably, the North China Plain (NCP) had the highest HONO emission density (3.51 kg N/ha/yr). Seasonal HONO emissions followed the order: summer (0.38 kg N/ha) > spring (0.19 kg N/ha) > autumn (0.17 kg N/ha) > winter (0.06 kg N/ha). Moreover, HONO emissions were strongly correlated with fertilization, cropland, temperature, and precipitation. This study provides vital scientific groundwork for the atmospheric nitrogen cycle and the formation of secondary pollutants.

Rapid visual nucleic acid detection of Vibrio alginolyticus by recombinase polymerase amplification combined with CRISPR/Cas13a.

Vibrio alginolyticus (V. alginolyticus) is a common pathogen in the ocean. In addition to causing serious economic losses in aquaculture, it can also infect humans. The rapid detection of nucleic acids of V. alginolyticus with high sensitivity and specificity in the field is very important for the diagnosis and treatment of infection caused by V. alginolyticus. Here, we established a simple, fast and effective molecular method for the identification of V. alginolyticus that does not rely on expensive instruments and professionals. The method integrates recombinase polymerase amplification (RPA) technology with CRISPR system in a single PCR tube. Using this method, the results can be visualized by lateral flow dipstick (LFD) in less than 50 min, we named this method RPA-CRISPR/Cas13a-LFD. The method was confirmed to achieve high specificity for the detection of V. alginolyticus with no cross-reactivity with similar Vibrio and common clinical pathogens. This diagnostic method shows high sensitivity; the detection limit of the RPA-CRISPR/Cas13a-LFD is 10 copies/µL. We successfully identified 35 V. alginolyticus strains from a total of 55 different bacterial isolates and confirmed their identity by (Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, MALDI-TOF MS). We also applied this method on infected mice blood, and the results were both easily and rapidly obtained. In conclusion, RPA-CRISPR/Cas13a-LFD offers great potential as a useful tool for reliable and rapid diagnosis of V. alginolyticus infection, especially in limited conditions.

Gas Chromatographic-Ion Mobility Spectrometry Combined with Chemometrics to Study the Changes in Characteristic Odor Components of Galli gigerii Endothelium Corneum in Different Processing Methods.

Galli gigerii endothelium corneum (GGEC) is a traditional Chinese medicine commonly used in clinical practice to treat various conditions such as indigestion, vomiting, spermatorrhea, and enuresis. In this study, the volatile components of different concoctions of GGEC were examined by gas chromatography-ion mobility spectrometry (GC-IMS), and the changes of the components were compared by fingerprinting, combined with principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) to analyze the main volatile components and find out the different markers that can distinguish the different concoctions of GGEC. In the result, the GC-IMS fingerprints of GGEC and its different concoctions showed differences in their volatile components, of which 49 volatiles were clearly characterized, with some components including monomers and dimers. The characteristic volatile components of raw GGEC (SP) were n-nonanal, (E)-2-octenal, beta-ocimene, 2-ethyl-1-hexanol, etc. The characteristic volatile components of stir-fried GGEC (QC) are heptanal, 2-octanol, (E)-2-heptenal, etc. The characteristic volatile components of sand ironing GGEC (ST) are isoamyl acetate, decanal, cyclohexanone, 2-ethyl pyrazine, etc. The characteristic volatile components of stir-fried GGEC with vinegar (CZ) are thiazole, linalool, 2,3,5-trimethylpyrazine, etc. The characteristic volatile components of stir-fried GGEC with milk (FH) are 2-methylbutanoic acid, ethyl acetate, ethyl 2-hydroxypropanoate, butyl acetate, etc. By chemometric analysis, components such as n-nonanal, (E)-2-octenal, 2-pentyl-furan, butanal, 1,4-dioxane, and 2-methylpropanoic acid could be used as difference markers to distinguish different concoction products of GGEC. Furthermore, by analyzing different volatile compounds, we can examine the changes in volatile components during processing of GGEC, which can provide experimental data for the identification and establishment of quality standards.

Improved ammonia emission inventory of fertilizer application for three major crops in China based on phenological data.

NH3 has an important impact on atmospheric chemistry, and its reduction has become a potential pathway to alleviate haze pollution. The existing NH3 emission inventories still have significant uncertainties in terms of their temporal distributions. In this study, we combined satellite remote-sensing phenological data with ground-station phenological data to develop a method for the temporal allocation of NH3 emissions from fertilizer application. A high-resolution dataset for fertilizer application in China was established. We developed NH3 emission inventories for the fertilization of three major crops in China, with a resolution of 1/12° × 1/12°. The results showed that there was a significant temporal variation in fertilizer application dates across the country, mainly concentrated in June (17.16 %), July (19.08 %), and August (18.77 %). The majority of fertilizer application for the three major crops occurred during the spring and summer months, with a particular emphasis on April (5.72 Tg), May (7.05 Tg), and June (4.29 Tg). The total NH3 emission from the three major crops in China in 2019 was 2.73 Tg. The North China Plain (762.23 Gg) and Middle and Lower Yangtze River Plain (606.85 Gg) were identified as the primary regions for high NH3 emissions from fertilizer application. The results also showed that NH3 emissions from the three major crops were predominantly observed during summer, with a peak value in July (606.99 Gg), mainly because of the high proportion of topdressing fertilizers. Areas with high fertilizer application generally coincided with areas of high NH3 emissions. This study may be the first to utilize remote-sensing phenological data to establish the NH3 emission inventory, which is of great significance for further improving the accuracy of the NH3 emission inventory.

A Novel Sample-to-Answer Visual Nucleic Acid Detection System for Adenovirus Detection.

Human adenoviruses (HAdVs) are common viruses that can cause local outbreaks in schools, communities and military camps, posing a huge threat to public health. An ideal POCT device for adenovirus detection in resource-limited settings is critical to control the spread of the virus. In this study, we developed an integrated and electricity-independent sample-to-answer system that can complete nucleic acid extraction, amplification, and detection at room temperature. This system is suitable for field and on-site detection because of its rapidity, sensitivity, lack of contamination, and lack of requirements of high-precision instruments and skilled technicians. It consists of two separate modules, ALP FINA (alkaline lysis with the paper-based filtration isolation of nucleic acid) and SV RPA (sealed and visual recombinase polymerase amplification). The extraction efficiency of ALP FINA can reach 48 to 84%, which is close to that of the conventional centrifuge column. The detection sensitivity of SV RPA is close to 10 copies/µL of AdvB and AdvE without aerosol contamination after repeated operations. When SV RPA was applied to the detection of nasopharyngeal swab samples of 19 patients who were infected with AdvB or AdvE as well as 10 healthy volunteers, its sensitivity and specificity reached 100%, respectively. IMPORTANCE HAdV infections are readily transmittable and, in some instances, highly contagious. Early and rapid diagnosis is essential for disease control. In this work, we developed a portable, disposable, and modularized sample-to-answer detection system for AdvB and AdvE, which rendered the entire test to be completely independent of electricity and other laboratory infrastructure. Thus, this detection system can be applied in resource-limited settings, and it has the potential to be further developed as an early diagnosis method in the field.

Atmospheric ammonia in China: Long-term spatiotemporal variation, urban-rural gradient, and influencing factors.

In recent years, atmospheric ammonia (NH3) concentrations have increased in China. Ammonia control has become one of the next hot topics in air pollution mitigation with the increasing cost of acid gas emission reduction. In this study, using Infrared Atmospheric Sounding Interferometer (IASI) satellite observations, we analyzed the spatiotemporal distribution, the urban-rural gradient of the vertical column densities (VCDs) of NH3 and the contribution of influencing factors (meteorology, social, atmospheric acid gases, and NH3 emissions) in China from 2008 to 2019 using hotspot analysis, circular gradient analysis, geographical and temporal weighted regression, and some other methods. Our results showed that NH3 VCDs in China have significantly increased (31.88 %) from 2008 to 2019, with the highest occurring in North China Plain. The average NH3 VCDs in urban areas were significantly higher than those in rural areas, and the urban-rural gap in NH3 VCDs was widening. The results of circular gradient analysis showed an overall decreasing trend in NH3 VCDs along the urban-rural gradient. We used a geographically and temporally weighted regression model to analyze the contribution of various influencing factors to NH3 VCDs: meteorology (30.13 %), social (27.40 %), atmospheric acid gases (23.20 %), and NH3 emissions (19.28 %) factors. The results showed substantial spatiotemporal differences in the influencing factors. Atmospheric acid gas was the main reason for the increase in NH3 VCDs from 2008 to 2019. A more thorough understanding of the spatiotemporal distribution, urban-rural variations, and factors influencing NH3 in China will aid in developing control strategies to reduce PM2.5.

Sigma-1 receptor agonist properties that mediate the fast-onset antidepressant effect of hypidone hydrochloride (YL-0919).

The most intriguing characteristic of the sigma-1 receptor is its ability to regulate multiple functional proteins directly via protein-protein interactions, giving the sigma-1 receptor the powerful ability to regulate several survival and metabolic functions in cells, fine tune neuronal excitability, and regulate the transmission of information within brain circuits. This characteristic makes sigma-1 receptors attractive candidates for the development of new drugs. Hypidone hydrochloride (YL-0919), a novel structured antidepressant candidate developed in our laboratory, possess a selective sigma-1 receptor agonist profile, as evidenced by molecular docking, radioligand receptor binding assays, and receptor functional experiments. In vivo studies have revealed that YL-0919 elicits a fast-onset antidepressant activity (within one week) that can be attenuated with pretreatment of the selective sigma-1 receptor antagonist, BD-1047. Taken together, the findings of the current study suggest that YL-0919 activates the sigma-1 receptor to partially mediate the rapid onset antidepressant effects of YL-0919. Thus, YL-0919 is a promising candidate as a fast-onset antidepressant that targets the sigma-1 receptor.

Autophagy Is Essential for Neural Stem Cell Proliferation Promoted by Hypoxia.

Hypoxia as a microenvironment or niche stimulates proliferation of neural stem cells (NSCs). However, the underlying mechanisms remain elusive. Autophagy is a protective mechanism by which recycled cellular components and energy are rapidly supplied to the cell under stress. Whether autophagy mediates the proliferation of NSCs under hypoxia and how hypoxia induces autophagy remain unclear. Here, we report that hypoxia facilitates embryonic NSC proliferation through HIF-1/mTORC1 signaling pathway-mediated autophagy. Initially, we found that hypoxia greatly induced autophagy in NSCs, while inhibition of autophagy severely impeded the proliferation of NSCs in hypoxia conditions. Next, we demonstrated that the hypoxia core regulator HIF-1 was necessary and sufficient for autophagy induction in NSCs. Considering that mTORC1 is a key switch that suppresses autophagy, we subsequently analyzed the effect of HIF-1 on mTORC1 activity. Our results showed that the mTORC1 activity was negatively regulated by HIF-1. Finally, we provided evidence that HIF-1 regulated mTORC1 activity via its downstream target gene BNIP3. The increased expression of BNIP3 under hypoxia enhanced autophagy activity and proliferation of NSCs, which was mediated by repressing the activity of mTORC1. We further illustrated that BNIP3 can interact with Rheb, a canonical activator of mTORC1. Thus, we suppose that the interaction of BNIP3 with Rheb reduces the regulation of Rheb toward mTORC1 activity, which relieves the suppression of mTORC1 on autophagy, thereby promoting the rapid proliferation of NSCs. Altogether, this study identified a new HIF-1/BNIP3-Rheb/mTORC1 signaling axis, which regulates the NSC proliferation under hypoxia through induction of autophagy.