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Pain emotion is a negative emotion caused by pain, which seriously affects the patients' physical and psychological health. The anterior cingulate cortex (ACC) is a key brain region in the occurrence and regulation of pain and painful emotion. In this paper, we summed up the relevant progress of researches on acupuncture improvement of pain emotion from neurotransmitters and receptors, cellular signaling pathways and neural circuits of ACC, in order to provide a basis for further research. 1) Acupuncture can regulate the long-term potentiation of ACC synaptic transmission by down-regulating the expression of N-methyl-D-aspartic acid receptor (NMDAR)； and up-regulating the expression of μ-, delta- and κ-opioid receptors, neuropeptide S (NPS)/ NPS receptor, and the number of parvalbumin-expressing interneurons to reduce neuronal excitability, relieving pain emotion； 2) Acupuncture can regulate synaptic transmission of ACC neurons by inhibiting protein kinase Mζ (PKMζ)-GluR1 and cAMP/PKA-ERK-CREB signaling pathways, and modulate synaptic plasticity to ameliorate pain emotion； 3) Acupuncture intervention induced inhibition of rostral ACC Glu -thalamic circuit may result in relief of pain emotion but not pain sensation, whereas inhibition of the rostral ACC Glu -ventrolateral periaqueductal gray matter(vlPAG) circuit may relieve pain sensation but not pain emotion. In addition, our team found that in the treatment of painful diseases by acupuncture, the addition of "spirit-regulating" acupoints can not only improve patients' negative emotion, but also significantly relive patients' pain sensation.

Depression is high in prevalence rate, recurrence rate and disability rate. Acupuncture is effective on depression. The paper reviewed the regulatory effect of acupuncture on five prominent signaling pathways, i.e. mitogen activated protein kinase (MAPK), Wnt/β-catenin, Notch, adenyl ate cyclase/cyclic adenosine phosphate/protein kinase (AC/cAMP/PKA) and NO/cyclic guanosine monophosphate (cGMP)； and elaborated the structure of each signaling pathway, the association with depression onset, and the relevant research progress of acupuncture in treatment of depression. In view of the regulation of signal pathways, acupuncture can up-regulate AC/cAMP/PKA and extracellular signal-regulated kinase (ERK), promote the expression of neurotrophic factors or Bcl-2, prevent from and repair neuronal damage, advance neurogenesis and improve synaptic plasticity； it can modulate the Wnt/β-catenin and Notch signal pathways to protect neurons and increase cell proliferation； and down-regulate JNK and up-regulate NO/cGMP signal pathways to inhibit stress that leads to abnormal apoptosis of neurosis and attenuate neurotoxicity and neuronal damage so that anti-depression of acupuncture is obtained. This review provides a new approach to the mechanism research of acupuncture in treatment of depression through regulating the relevant single pathways.

Catalytic bioparts are fundamental to the design, construction and optimization of biological systems for specific metabolic pathways. However, the functional characterization information of these bioparts is frequently dispersed across multiple databases and literature sources, posing significant challenges to the effective design and optimization of specific chassis or cell factories. We developed the Registry and Database of Bioparts for Synthetic Biology (RDBSB), a comprehensive resource encompassing 83 193 curated catalytic bioparts with experimental evidences. RDBSB offers their detailed qualitative and quantitative catalytic information, including critical parameters such as activities, substrates, optimal pH and temperature, and chassis specificity. The platform features an interactive search engine, visualization tools and analysis utilities such as biopart finder, structure prediction and pathway design tools. Additionally, RDBSB promotes community engagement through a catalytic bioparts submission system to facilitate rapid data sharing and utilization. To date, RDBSB has supported the contribution of >1000 catalytic bioparts. We anticipate that the database will significantly enhance the resources available for pathway design in synthetic biology and serve essential tools for researchers. RDBSB is freely available at https://www.biosino.org/rdbsb/., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Salivary glands are the principal organs responsible for secreting saliva in the oral cavity. Tumors, trauma, inflammation, and other factors can cause functional or structural damage to the glands, leading to reduced saliva secretion. In this study, we innovatively prepared a acinar-mimetic silk fibroin-collagen-astragalus polysaccharide (SCA) scaffold using low-temperature three-dimensional (3D) printing and freeze-drying techniques. We evaluated the material properties and cell compatibility of the scaffold in vitro and implanted it into the damaged parotid glands (PG) of rats to assess its efficacy in tissue reconstruction and functional repair. The results demonstrated that the SCA scaffold featured a porous structure resembling natural acini, providing an environment conducive to cell growth and orderly aggregation. It exhibited excellent porosity, water absorption, mechanical properties, and biocompatibility, fulfilling the requirements for tissue engineering scaffolds. In vitro, the scaffold facilitated adhesion, proliferation, orderly polarization, and spherical aggregation of PG cells. In vivo, the SCA scaffold effectively recruited GECs locally, forming gland-like acinar structures that matured gradually, promoting the regeneration of damaged PGs. The SCA scaffold developed in this study supports tissue reconstruction and functional repair of damaged PGs, making it a promising implant material for salivary gland regeneration., Competing Interests: Declaration of competing interest I have nothing to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Purpose: Exploring the effects of acupuncture at the "Yizhi Tiaoshen" acupoint on blood oxygen metabolism and neurological function changes in the brain regions of AD model rats., Methods: The AD model was replicated by intraperitoneal injection of D-galactose combined with bilateral hippocampal CA1 injection of Okadaic acid (OA). Thirty rats with successfully replicated model were selected through Morris water maze experiment and randomly divided into model group, donepezil hydrochloride group, and acupuncture group, with 10 rats in each group. After treatment, fNIRs were used to detect changes in Oxy Hb, Deoxy Hb, and Total Hb in the cerebral cortex of rats in each group, in order to evaluate the neurological function changes in key brain areas., Results: The escape latency of the donepezil hydrochloride group and the acupuncture group was shortened, the number of crossings through the original platform increased, and the duration of stay in the quadrant where the original platform was located was prolonged. Based on fNIRs detection, the main differential channels of blood oxygen metabolism in AD rats were identified as 2-2 and 8-7, corresponding to the prefrontal and parietal lobes, respectively. The concentrations of Oxy Hb and Total Hb were significantly increased in both treatment groups, while the concentration of Deoxy Hb was significantly decreased., Conclusion: Acupuncture with the "Yizhi Tiaoshen" acupoint formula and donepezil hydrochloride can improve the learning and memory function of AD rats, and its mechanism may be related to improving blood oxygen metabolism in the prefrontal and parietal regions and protecting neuronal function., Competing Interests: The authors declare that they have no conflicts of interest for this work., (© 2024 Zhang et al.)

Wildfires generate abundant smoke primarily composed of fine-mode aerosols. However, accurately measuring the fine-mode aerosol optical depth (fAOD) is highly uncertain in most existing satellite-based aerosol products. Deep learning offers promise for inferring fAOD, but little has been done using multiangle satellite data. We developed an innovative angle-dependent deep-learning model (ADLM) that accounts for angular diversity in dual-angle observations. The model captures aerosol properties observed from dual angles in the contiguous United States and explores the potential of Greenhouse gases Observing Satellite-2's (GOSAT-2) measurements to retrieve fAOD at a 460 m spatial resolution. The ADLM demonstrates a strong performance through rigorous validation against ground-based data, revealing small biases. By comparison, the official fAOD product from the Moderate Resolution Imaging Spectroradiometer (MODIS), the Visible Infrared Imaging Radiometer Suite (VIIRS), and the Multiangle Imaging Spectroradiometer (MISR) during wildfire events is underestimated by more than 40% over western USA. This leads to significant differences in estimates of aerosol radiative forcing (ARF) from wildfires. The ADLM shows more than 20% stronger ARF than the MODIS, VIIRS, and MISR estimates, highlighting a greater impact of wildfire fAOD on Earth's energy balance.

Camptothecin (CPT) is a monoterpenoid indole alkaloid with a wide spectrum of anticancer activity. However, its application is hindered by poor solubility, lack of targeting specificity, and severe side effects. Structural derivatization of CPT and the development of suitable drug delivery systems are potential strategies for addressing these issues. In this study, we discovered that the protein Cytochrome P450 Family 1 Subfamily A Member 1 (CYP1A1) from Homo sapiens catalyzes CPT to yield 9-hydroxycamptothecin (9-HCPT), which exhibits increased water solubility and cytotoxicity. We then created a RNA-protein complex based drug delivery system with enzyme and pH responsiveness and improved the targeting and stability of the nanomedicine through protein module assembly. The subcellular localization of nanoparticles can be visualized using fluorescent RNA probes. Our results not only identified the protein CYP1A1 responsible for the structural derivatization of CPT to synthesize 9-HCPT but also offered potential strategies for enhancing the utilization of silk-based drug delivery systems in tumor therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this article, a novel approach of prescribed performance synchronization control is developed for heterogeneous nonlinear multiagent systems (MASs) subject to unknown actuator faults. Considering that not all followers are able to access the information of the leader, a distributed auxiliary perception system is proposed to estimate the state information of the leader to guarantee that the estimation errors converge to zero within fixed time. Then, based on the estimated states, a prescribed performance fault-tolerant control (FTC) approach is proposed, which achieves the user-defined performance specifications even in the presence of system faults. Moreover, as accurate system dynamic models are perhaps hard to acquire in practical engineering, a data-based method is proposed by using the reinforcement learning (RL) algorithm to design the fault-tolerant controller, which only needs the off-policy online data and is independent of the model dynamics of followers. The stability and synchronization with the prescribed behavior are guaranteed through the Lyapunov stability theorem. Finally, simulation results are presented to illustrate the effectiveness of the developed controller.

Objective To investigate the effects of sakuranetin (SK) on motor functions in the mouse model of spinal cord injury (SCI) and decipher the mechanism.Methods Fifty-four C57BL/6J mice were randomized into sham,SCI,and SK groups.The mice in the sham group underwent only laminectomy at T9,while those in the SCI and SK groups were subjected to spinal cord contusion injury at T9.Behavioral tests were conducted at different time points after surgery to evaluate the motor functions of mice in each group.The pathological changes in the tissue were observed to assess the extent of SCI in each group.The role and mechanism of SK in SCI were predicted by gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment analyses.Reverse transcription real-time fluorescence quantitative PCR,ELISA,and immunofluorescence were employed to evaluate the inflammation and activation of microglia in SCI mice.BV2 cells in vitro were classified into control (Con),lipopolysaccharide (LPS),and LPS+SK groups.The effects of SK intervention on the release of inflammatory cytokines and the activation of BV2 cells were evaluated.Furthermore,the phosphatidylinositol-3-kinase(PI3K)/protein kinase B (AKT) signaling pathway activator insulin-like growth factor-1 (IGF-1) was used to treat the SK-induced BV2 cells in vitro (SK+IGF-1 group),and SK was used to treat the IGF-1-induced BV2 cells in vitro (IGF-1+SK group).Western blotting was conducted for molecular mechanism validation.Results Behavioral tests and histological staining results showed that compared with the SCI group,the SK group exhibited improved motor abilities and reduced area of damage in the spinal cord tissue (all P<0.001).The GO enrichment analysis predicted that SK may be involved in the inflammation following SCI.The KEGG enrichment analysis predicted that SK regulated the PI3K/Akt pathway to exert the neuroprotective effect.The results from in vitro and in vivo experiments showed that SK lowered the levels of tumor necrosis factor-α,interleukin-6,and interleukin-1β and inhibited the activation of microglia (all P<0.05).The results of Western blotting showed that SK down-regulated the phosphorylation levels of PI3K and Akt (all P<0.001) and inhibited the IGF-1-induced elevation of PI3K and Akt phosphorylation levels (all P<0.001).Conversely,IGF-1 had the opposite effects (P=0.001,P<0.001).The results of reverse transcription real-time fluorescence quantitative PCR,ELISA,and immunofluorescence showed that the SK+IGF-1 group had higher levels of inflammatory cytokines and more activated microglia than the SK group(all P<0.05).Conclusion SK may suppress the activation of the PI3K/Akt pathway to inhibit the inflammation mediated by SCI-induced activation of microglia,ameliorate the pathological damage of the spinal cord tissue,and promote the recovery of motor functions in SCI mice.

Cobalt phosphide has received much attention as an efficient catalyst for electrocatalytic hydrodechlorination (EHDC). However, the active species proton hydrogen (H*) is consumed by the hydrogen evolution reaction (HER). Herein, we report a crystal regulation strategy for cobalt phosphate/graphitic nanocarbon/nickel foam (CoPO/GC/NF) catalysts applied for the EHDC of 2,4-dichlorophenoxyacetic acid (2,4-D). Characterization revealed that during the high-temperature phosphatization process, CoPO/GC/NF catalysts developed Co(PO 3 ) 2 @CoP heterojunctions, enhancing charge transfer at the electrolyte-catalyst interface and water dissociation. The interaction between Co(PO 3 ) 2 and CoP induced the reconstitution of CoP into the Co-OH species, which facilitated the production of H* by accelerating the Volmer step, enhancing EHDC activity. Furthermore, Co(PO 3 ) 2 species improve the catalyst tolerance, with CoPO/GC/NF(450) maintaining over 71% yield of phenoxyacetic acid (PA) in continuous testing for up to 80 h under high-salt conditions. This work clarifies the surface transformation process of CoP/GC/NF during hydrodechlorination and demonstrates great potential for chlorophenol wastewater remediation.

Alzheimer's disease (AD) is a neurodegenerative disease with high incidence in the elderly population, and the synaptic changes in central neurons are the key pathological feature. The clinical effect of acupuncture and moxibustion in the treatment of AD is positive, and the research on the mechanism of acupuncture intervention of AD from the perspective of central synaptic plasticity regulation has been conducted uninterruptedly. In the present paper, we made a summation about the relevant experimental studies in recent years, and analyzed its mechanisms underlying improvement of AD by regulating synaptic plasticity from 1) repairing synaptic structure (synaptic contact area ［total number of synapses, synaptic surface density, synaptic number density］, postsynaptic dense zone thickness, synaptic gap width, and interface curvature), 2) improving synaptic transmission efficiency (regulating long-term potentiation and long-term depression), 3) promoting the expression of synapse related proteins (synaptophysin, postsynaptic density protein 95, growth associated protein 43), 4) regulating the expression of neurotransmitters (acetylcholine, monoamines, amino acids, etc.) and receptors (α7 nicotinic acetylcholine receptor, glutaminergic receptor, etc.), and 5) improving the level of neurotrophic factors (brain derived neurotrophic factor, BDNF) and BDNF/SYN/microtubule-associated protein 2 signaling, etc., hoping to provide a reference for future studies.

Fine-mode aerosol optical depth (fAOD) is a vital proxy for the concentration of anthropogenic aerosols in the atmosphere. Currently, the limited data length and high uncertainty of the satellite-based data diminish the applicability of fAOD for climate research. Here, we propose a novel pretrained deep learning framework that can extract information underlying each satellite pixel and use it to create new latent features that can be employed for improving retrieval accuracy in regions without in situ data. With the proposed model, we developed a new global fAOD (at 0.5 μm) data from 2001 to 2020, resulting in a 10% improvement in the overall correlation coefficient ( R ) during site-based independent validation and a 15% enhancement in non-AERONET site areas validation. Over the past two decades, there has been a noticeable downward trend in global fAOD (-1.39 × 10 -3 /year). Compared to the general deep-learning model, our method reduces the global trend's previously overestimated magnitude by 7% per year. China has experienced the most significant decline (-5.07 × 10 -3 /year), which is 3 times greater than the global trend. Conversely, India has shown a significant increase (7.86 × 10 -4 /year). This study bridges the gap between sparse in situ observations and abundant satellite measurements, thereby improving predictive models for global patterns of fAOD and other climate factors.

This paper proposes an observer-based hierarchical distributed model predictive control (MPC) strategy for ensuring speed consistency in multi-linear motor traction systems. First, a communication topology is considered to ensure information exchange. Secondly, the control architecture of each agent is divided into upper layers and lower layers. The upper layer utilizes a distributed MPC method to track the leader's speed. The lower layer uses a decentralized MPC method to track the command signals sent by its upper layer controller. In addition, to eliminate the negative impact of disturbance, a nonlinear disturbance observer is designed. We then prove the asymptotic stability of the entire system by properly designing the Lyapunov equation. Finally, the feasibility of the proposed strategy is verified based on several simulations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 ISA. Published by Elsevier Ltd. All rights reserved.)

The denitrification process in aquaculture systems plays a crucial role in nitrogen (N) cycle and N budget estimation. Reliable models are needed to rapidly quantify denitrification rates and assess nitrogen losses. This study conducted a comparative analysis of denitrification rates in fish, crabs, and natural ponds in the Taihu region from March to November 2021, covering a complete aquaculture cycle. The results revealed that aquaculture ponds exhibited higher denitrification rates compared to natural ponds. Key variables influencing denitrification rates were Nitrate nitrogen (NO 3 - -N), Suspended particles (SPS), and chlorophyll a (Chla). There was a significant positive correlation between SPS concentration and denitrification rates. However, we observed that the denitrification rate initially rose with increasing Chla concentration, followed by a subsequent decline. To develop parsimonious models for denitrification rates in aquaculture ponds, we constructed five different statistical models to predict denitrification rates, among which the improved quadratic polynomial regression model (SQPR) that incorporated the three key parameters accounted for 80.7% of the variability in denitrification rates. Additionally, a remote sensing model (RSM) utilizing SPS and Chla explained 43.8% of the variability. The RSM model is particularly valuable for rapid estimation in large regions where remote sensing data are the only available source. This study enhances the understanding of denitrification processes in aquaculture systems, introduces a new model for estimating denitrification in aquaculture ponds, and offers valuable insights for environmental management., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Background: Silicosis is an irreversible fibrotic disease of the lung caused by chronic exposure to silica dust, which manifests as infiltration of inflammatory cells, excessive secretion of pro-inflammatory cytokines, and pulmonary diffuse fibrosis. As the disease progresses, lung function further deteriorates, leading to poorer quality of life of patients. Currently, few effective drugs are available for the treatment of silicosis. Bicyclol (BIC) is a compound widely employed to treat chronic viral hepatitis and drug-induced liver injury. While recent studies have demonstrated anti-fibrosis effects of BIC on multiple organs, including liver, lung, and kidney, its therapeutic benefit against silicosis remains unclear. In this study, we established a rat model of silicosis, with the aim of evaluating the potential therapeutic effects of BIC., Methods: We constructed a silicotic rat model and administered BIC after injury. The FlexiVent instrument with a forced oscillation system was used to detect the pulmonary function of rats. HE and Masson staining were used to assess the effect of BIC on silica-induced rats. Macrophages-inflammatory model of RAW264.7 cells, fibroblast-myofibroblast transition (FMT) model of NIH-3T3 cells, and epithelial-mesenchymal transition (EMT) model of TC-1 cells were established in vitro. And the levels of inflammatory mediators and fibrosis-related proteins were evaluated in vivo and in vitro after BIC treatment by Western Blot analysis, RT-PCR, ELISA, and flow cytometry experiments., Results: BIC significantly improved static compliance of lung and expiratory and inspiratory capacity of silica-induced rats. Moreover, BIC reduced number of inflammatory cells and cytokines as well as collagen deposition in lungs, leading to delayed fibrosis progression in the silicosis rat model. Further exploration of the underlying molecular mechanisms revealed that BIC suppressed the activation, polarization, and apoptosis of RAW264.7 macrophages induced by SiO 2 . Additionally, BIC inhibited SiO 2 -mediated secretion of the inflammatory cytokines IL-1β, IL-6, TNF-α, and TGF-β1 in macrophages. BIC inhibited FMT of NIH-3T3 as well as EMT of TC-1 in the in vitro silicosis model, resulting in reduced proliferation and migration capability of NIH-3T3 cells. Further investigation of the cytokines secreted by macrophages revealed suppression of both FMT and EMT by BIC through targeting of TGF-β1. Notably, BIC blocked the activation of JAK2/STAT3 in NIH-3T3 cells required for FMT while preventing both phosphorylation and nuclear translocation of SMAD2/3 in TC-1 cells necessary for the EMT process., Conclusion: The collective data suggest that BIC prevents both FMT and EMT processes, in turn, reducing aberrant collagen deposition. Our findings demonstrate for the first time that BIC ameliorates inflammatory cytokine secretion, in particular, TGF-β1, and consequently inhibits FMT and EMT via TGF-β1 canonical and non-canonical pathways, ultimately resulting in reduction of aberrant collagen deposition and slower progression of silicosis, supporting its potential as a novel therapeutic agent., (© 2024. The Author(s).)

As a practical chemical energy conversion technology, electrocatalysis could be used in fields of energy conversion and environmental protection. In recent years, significant research efforts have been devoted to the design and development of high-performance electrocatalysts because the rational design of catalysts is crucial for enhancing electrocatalytic performance. Creating electrocatalysts by forming interactions between different components at the interface is an important means of controlling and improving performance. Therefore, several common interfacial binding forces used for synthesizing electrocatalysts was systematically summarized in this review for the first time. The discussion revolves around the crucial roles these binding forces play in various electrocatalytic reaction processes. Various characterization techniques capable of proving the existence of these interfacial binding forces was also involved in the review. Finally, some prospects and challenges for designing and researching materials through the utilization of interfacial binding forces were presented., (© 2024 Wiley-VCH GmbH.)

Pregabalin is a medication primarily used in the treatment of neuropathic pain and anxiety disorders, owing to its gabapentinoid properties. Pregabalin monotherapy faces limitations due to its variable efficacy and dose-dependent adverse reactions. In this study, we conducted a comprehensive investigation into the potentiation of pregabalin's analgesic effects by dexborneol, a neuroprotective bicyclic monoterpenoid compound. We performed animal experiments where pain models were induced using two methods: peripheral nerve injury, involving axotomy and ligation of the tibial and common peroneal nerves, and incisional pain through a longitudinal incision in the hind paw, while employing a multifaceted methodology that integrates behavioral pharmacology, molecular biology, neuromorphology, and lipidomics to delve into the mechanisms behind this potentiation. Dexborneol was found to enhance pregabalin's efficacy by promoting its transportation to the central nervous system, disrupting self-amplifying vicious cycles via the reduction of HMGB1 and ATP release, and exerting significant anti-oxidative effects through modulation of central lipid metabolism. This combination therapy not only boosted pregabalin's analgesic property but also notably decreased its side effects. Moreover, this therapeutic cocktail exceeded basic pain relief, effectively reducing neuroinflammation and glial cell activation-key factors contributing to persistent and chronic pain. This study paves the way for more tolerable and effective analgesic options, highlighting the potential of dexborneol as an adjuvant to pregabalin therapy.

Aquaculture systems are expected to act as potential hotspots for nitrous oxide (N 2 O) emissions, largely attributed to substantial nutrient loading from aquafeed applications. However, the specific patterns and contributions of N 2 O fluxes from these systems to the global emissions inventory are not well characterized due to limited data. This study investigates the patterns of N 2 O flux across 127 freshwater systems in China to elucidate the role of aquaculture ponds and lakes/reservoirs in landscape N 2 O emission. Our findings show that the average N 2 O flux from aquaculture ponds was 3.63 times higher (28.73 μg N 2 O m -2 h -1 ) than that from non-aquaculture ponds. Additionally, the average N 2 O flux from aquaculture lakes/reservoirs (15.65 μg N 2 O m -2 h -1 ) increased 3.05 times compared to non-aquaculture lakes/reservoirs. The transition from non-aquaculture to aquaculture practices has resulted in a net annual increase of 7589 ± 2409 Mg N 2 O emissions in China's freshwater systems from 2003 to 2022, equivalent to 20% of total N 2 O emissions from China's inland water. Particularly, the robust negative regression relationship between N 2 O emission intensity and water area suggests that small ponds are hotspots of N 2 O emissions, a result of both elevated nutrient concentrations and more vigorous biogeochemical cycles. This indicates that N 2 O emissions from smaller aquaculture ponds are larger per unit area compared to equivalent larger water bodies. Our findings highlight that N 2 O emissions from aquaculture systems can not be proxied by those from natural water bodies, especially small water bodies exhibiting significant but largely unquantified N 2 O emissions. In the context of the rapid global expansion of aquaculture, this underscores the critical need to integrate aquaculture into global assessments of inland water N 2 O emissions to advance towards a low-carbon future., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with pure severe aortic regurgitation (PSAR) who are contraindicated for surgery or have a high surgical risk. However, the therapeutic efficacy and safety of TAVR in low Society of Thoracic Surgeons (STS) score risk patients remain to be clarified. This study aimed to explore the feasibility of TAVR treatment in different STS-risk patients and to compare the adverse events between the groups. In this study, patients with PSAR who underwent TAVR at Zhongshan Hospital, Fudan University, China, during the inclusion period were included and categorized into 3 groups based on STS scores. The baseline data, imaging results, and follow-up data of the patients were documented. Therefore, of 75 TAVR patients, 38 (50.7%) were categorized as low risk (STS <4), and 37 (49.3%) patients were categorized as intermediate and high risk (STS ≥4). Compared with patients at intermediate and high risk, those in the low-risk group were younger, had a lower body mass index, had a lower prevalence of hypertension, chronic obstructive pulmonary disease, and previous percutaneous coronary intervention, and had better cardiac function (p all <0.05). In the hospital and at the 1-month follow-up, the degree of aortic regurgitation and cardiac function were significantly improved. No significant difference was found between the 2 groups in the hospital or during the 30-day follow-up. In conclusion, TAVR for PSAR in low-STS-risk patients is safe and efficient during 30 days of follow-up compared with intermediate- and high-STS-risk groups. TAVR for PSAR should not be limited to inoperable or STS-defined high-risk patients. Long-term follow-up is needed for further investigation., Competing Interests: Declaration of competing interest The authors have no competing interests to declare., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Ganoderma lucidum , a fungus used in traditional Chinese medicine, is known for its medicinal value attributed to its active components called Ganoderma triterpenoids (GTs). However, the limited isolation rate of these GTs has hindered their potential as promising drug candidates. Therefore, it is imperative to achieve large-scale preparation of GTs. In this study, four GTs were effectively synthesised from lanosterol. The antitumor activity of these GTs was evaluated in vivo . Endertiin B exhibited potent inhibitory activity against breast cancer cells (9.85 ± 0.91 μM and 12.12 ± 0.95 μM). Further investigations demonstrated that endertiin B significantly upregulated p21 and p27 and downregulated cyclinD1 expression, arresting the cell cycle at the G0/G1 phase and inducing apoptosis by decreasing BCL-2 and increasing BAX and BAK levels. Additionally, endertiin B was found to reduce the expression of proteins associated with the PI3K-AKT signaling pathway. To summarize, endertiin B effectively inhibited cell proliferation by blocking the cell cycle and inducing apoptosis through the PI3K-AKT pathway.

Silk fibroin (SF) from the cocoon of silkworm has exceptional mechanical properties and biocompatibility and is used as a biomaterial in a variety of fields. Sustainable, affordable, and scalable manufacturing of SF would enable its large-scale use. We report for the first time the high-level secretory production of recombinant SF peptides in engineered Pichia pastoris cell factories and the processing thereof to nanomaterials. Two SF peptides (BmSPR3 and BmSPR4) were synthesized and secreted by P. pastoris using signal peptides and appropriate spacing between hydrophilic sequences. By strain engineering to reduce protein degradation, increase glycyl-tRNA supply, and improve protein secretion, we created the optimized P. pastoris chassis PPGSP-8 to produce BmSPR3 and BmSPR4. The SF fed-batch fermentation titers of the resulting two P. pastoris cell factories were 11.39 and 9.48 g/L, respectively. Protein self-assembly was inhibited by adding Tween 80 to the medium. Recombinant SF peptides were processed to nanoparticles (NPs) and nanofibrils. The physicochemical properties of nanoparticles R3NPs and R4NPs from the recombinant SFs synthesized in P. pastoris cell factories were similar or superior to those of RSFNPs (Regenerated Silk Fibroin NanoParticles) originating from commercially available SF. Our work will facilitate the production by microbial fermentation of functional SF for use as a biomaterial., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Acupuncture treatment for depression has definite therapeutic efficacy, and its mechanism has been extensively studied. The extracellular regulatory protein kinase(ERK) signaling pathway is involved in the development and progression of depression. This article reviewed and summarized the research progress on the regulation of the ERK signaling pathway by acupuncture in the treatment of depression in recent years, focusing on the physiological activation and regulatory mechanism of the ERK signaling pathway, its association with the occurrence of depression, and the mechanisms through which acupuncture activates the ERK signaling pathway to treat depression (including enhancing neuronal synaptic plasticity, promoting the release of neurotrophic factors, and inhibiting neuronal apoptosis). Future research could explore the relationship between the ERK pathway and other pathways, investigate other brain regions besides the prefrontal cortex and hippocampus, examine differences in regulatory mechanisms between male and female patients, assess the effects of different acupuncture techniques on the ERK pathway, and increase efforts to explore mechanism of synaptic plasticity regulation, so as to provide reference for the clinical application and mechanism sludy of acupuncture in depression treatment.

Background: Inaccurate Forrest classification may significantly affect clinical outcomes, especially in high risk patients. Therefore, this study aimed to develop a real-time deep convolutional neural network (DCNN) system to assess the Forrest classification of peptic ulcer bleeding (PUB)., Methods: A training dataset (3868 endoscopic images) and an internal validation dataset (834 images) were retrospectively collected from the 900th Hospital, Fuzhou, China. In addition, 521 images collected from four other hospitals were used for external validation. Finally, 46 endoscopic videos were prospectively collected to assess the real-time diagnostic performance of the DCNN system, whose diagnostic performance was also prospectively compared with that of three senior and three junior endoscopists., Results: The DCNN system had a satisfactory diagnostic performance in the assessment of Forrest classification, with an accuracy of 91.2% (95%CI 89.5%-92.6%) and a macro-average area under the receiver operating characteristic curve of 0.80 in the validation dataset. Moreover, the DCNN system could judge suspicious regions automatically using Forrest classification in real-time videos, with an accuracy of 92.0% (95%CI 80.8%-97.8%). The DCNN system showed more accurate and stable diagnostic performance than endoscopists in the prospective clinical comparison test. This system helped to slightly improve the diagnostic performance of senior endoscopists and considerably enhance that of junior endoscopists., Conclusion: The DCNN system for the assessment of the Forrest classification of PUB showed satisfactory diagnostic performance, which was slightly superior to that of senior endoscopists. It could therefore effectively assist junior endoscopists in making such diagnoses during gastroscopy., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Accurate fine-mode and coarse-mode aerosol knowledge is crucial for understanding their impacts on the climate and Earth's ecosystems. However, current satellite-based Fine-Mode Aerosol Optical Depth (FAOD) and Coarse-Mode Aerosol Optical Depth (CAOD) methods have drawbacks including inaccuracies, low spatial coverage, and limited temporal duration. To overcome these issues, we developed new global-scale FAOD and CAOD from 2005 to 2020 using a novel deep learning model capable of the synergistic retrieval of two aerosol sizes. After validation with the aerosol robotic network (AERONET) and sky radiometer network (SKYNET), the new monthly FAOD and CAOD showed significant improvements in accuracy and spatial coverage. From 2005 to 2020, the new data showed that China had the greatest decrease in FAOD and CAOD. In contrast, India and South Latin America had a significant increase in FAOD versus North Africa in CAOD. FAOD in the regions of Argentina, Paraguay, and Uruguay in South America have shown an upward trend. The results reveal that FAOD and CAOD display distinct patterns of change in the same regions, particularly on the west coast of the United States where FAOD is increasing, while CAOD is decreasing. Aside from the year 2020 due to the global COVID-19 pandemic, the analysis showed that although China has seen at least an +85% increase in energy consumption and urban expansion in 2019 compared to 2005 due to the needs of development and construction, the implementation of China's air pollution control policies has led to a significant decrease in FAOD (-46%) and CAOD (-65%) after 2013. This research enriches our comprehension of global fine and coarse aerosol patterns, additional investigations are needed to determine the potential global implications of these changes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Using the self-developed fused indium wetting technology and planar waveguide, the uniform heat dissipation of the slab crystal and uniform pumping of the pump light were achieved, respectively. Based on the master oscillator power amplification (MOPA) scheme, the power was then amplified when the seed light source passed through the Nd:YAG slab crystal three times. Additionally, the image transfer system that we added to the amplified optical path achieved high beam quality. Finally, we obtained a rectangular pulsed laser with an output average power of 4461 W, a repetition frequency of 20 kHz, a pulse width of 62 ns, an optical-to-optical conversion efficiency of 26.8%, and a beam quality of β x =7.0 and β y =7.7.

Epigenetic modifications of chromatin, including histone acetylation, and tumor angiogenesis play pivotal roles in creating an immunosuppressive tumor microenvironment. In the randomized phase 2 CAPability-01 trial, we investigated the potential efficacy of combining the programmed cell death protein-1 (PD-1) monoclonal antibody sintilimab with the histone deacetylase inhibitor (HDACi) chidamide with or without the anti-vascular endothelial growth factor (VEGF) monoclonal antibody bevacizumab in patients with unresectable chemotherapy-refractory locally advanced or metastatic microsatellite stable/proficient mismatch repair (MSS/pMMR) colorectal cancer. Forty-eight patients were randomly assigned to either the doublet arm (sintilimab and chidamide, n = 23) or the triplet arm (sintilimab, chidamide and bevacizumab, n = 25). The primary endpoint of progression-free survival (PFS) rate at 18 weeks (18wPFS rate) was met with a rate of 43.8% (21 of 48) for the entire study population. Secondary endpoint results include a median PFS of 3.7 months, an overall response rate of 29.2% (14 of 48), a disease control rate of 56.3% (27 of 48) and a median duration of response of 12.0 months. The secondary endpoint of median overall survival time was not mature. The triplet arm exhibited significantly improved outcomes compared to the doublet arm, with a greater 18wPFS rate (64.0% versus 21.7%, P = 0.003), higher overall response rate (44.0% versus 13.0%, P = 0.027) and longer median PFS rate (7.3 months versus 1.5 months, P = 0.006). The most common treatment-emergent adverse events observed in both the triplet and doublet arms included proteinuria, thrombocytopenia, neutropenia, anemia, leukopenia and diarrhea. There were two treatment-related fatalities (hepatic failure and pneumonitis). Analysis of bulk RNA sequencing data from the patients suggested that the triplet combination enhanced CD8 + T cell infiltration, resulting in a more immunologically active tumor microenvironment. Our study suggests that the combination of a PD-1 antibody, an HDACi, and a VEGF antibody could be a promising treatment regimen for patients with MSS/pMMR advanced colorectal cancer. ClinicalTrials.gov registration: NCT04724239 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Background: Asthma affects 3% of the global population, leading to over 0.25 million deaths. Due to its complexity, asthma is difficult to cure or prevent, and current therapies have limitations. This has led to a growing demand for alternative asthma treatments. We found rosmarinic acid (RosA) as a potential new drug candidate from natural medicine. However, RosA has poor bioavailability and remains mainly in the gastrointestinal tract after oral administration, suggesting the involvement of gut microbiota in its bioactivity., Purpose: To investigate the mechanism of RosA in alleviating allergic asthma by gut-lung axis., Methods: We used 16S rRNA gene sequencing and metabolites analysis to investigate RosA's modulation of gut microbiota. Techniques of molecular biology and metabolomics were employed to study the pharmacological mechanism of RosA. Cohousing was used to confirm the involvement of gut microbiota in RosA-induced improvement of allergic asthma., Results: RosA decreased cholate levels from spore-forming bacteria, leading to reduced 5-hydroxytryptamine (5-HT) synthesis, bronchoconstriction, vasodilation, and inflammatory cell infiltration. It also increased short-chain fatty acids (SCFAs) levels, facilitating the expression of intestinal tight junction proteins to promote intestinal integrity. SCFAs upregulated intestinal monocarboxylate transporters (MCTs), thereby improving their systemic delivery to reduce Th2/ILC2 mediated inflammatory response and suppress eosinophil influx and mucus production in lung. Additionally, RosA inhibited lipopolysaccharide (LPS) production and translocation, leading to reduced TLR4-NFκB mediated pulmonary inflammation and oxidative stress., Conclusions: The anti-asthmatic mechanism of oral RosA is primarily driven by modulation of gut microbiota-derived 5-HT, SCFAs, and LPS, achieving a combined synergistic effect. RosA is a safe, effective, and reliable drug candidate that could potentially replace glucocorticoids for asthma treatment., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest, and all authors report no conflicts of interest in this work., (Copyright © 2024. Published by Elsevier GmbH.)

Patients with high tumor mutational burden (TMB) levels do not consistently respond to immune checkpoint inhibitors (ICIs), possibly because a high TMB level does not necessarily result in adequate infiltration of CD8 + T cells. Using bulk ribonucleic acid sequencing (RNA-seq) data from 9311 tumor samples across 30 cancer types, we developed a novel tool called the modulator of TMB-associated immune infiltration (MOTIF), which comprises genes that can determine the extent of CD8 + T cell infiltration prompted by a certain TMB level. We confirmed that MOTIF can accurately reflect the integrity and defects of the cancer-immunity cycle. By analyzing 84 human single-cell RNA-seq datasets from 32 types of solid tumors, we revealed that MOTIF can provide insights into the diverse roles of various cell types in the modulation of CD8 + T cell infiltration. Using pretreatment RNA-seq data from 13 ICI-treated cohorts, we validated the use of MOTIF in predicting CD8 + T cell infiltration and ICI efficacy. Among the components of MOTIF, we identified EMC3 as a negative regulator of CD8 + T cell infiltration, which was validated via in vivo studies. Additionally, MOTIF provided guidance for the potential combinations of programmed death 1 blockade with certain immunostimulatory drugs to facilitate CD8 + T cell infiltration and improve ICI efficacy., (Copyright © 2024 Science China Press. Published by Elsevier B.V. All rights reserved.)

Taxol is a widely-applied anticancer drug that inhibits microtubule dynamics in actively replicating cells. Although a minimum 19-step biosynthetic pathway has been proposed and 16 enzymes likely involved have been characterized, stepwise biosynthetic reactions from the well-characterized di-oxygenated taxoids to Taxol tetracyclic core skeleton are yet to be elucidated. Here, we uncover the biosynthetic pathways for a few tri-oxygenated taxoids via confirming the critical reaction order of the second and third hydroxylation steps, unearth a taxoid 9α-hydroxylase catalyzing the fourth hydroxylation, and identify CYP725A55 catalyzing the oxetane ester formation via a cascade oxidation-concerted acyl rearrangement mechanism. After identifying a acetyltransferase catalyzing the formation of C7-OAc, the pathway producing the highly-oxygenated 1β-dehydroxybaccatin VI with the Taxol tetracyclic core skeleton is elucidated and its complete biosynthesis from taxa-4(20),11(12)-diene-5α-ol is achieved in an engineered yeast. These systematic studies lay the foundation for the complete elucidation of the biosynthetic pathway of Taxol., (© 2024. The Author(s).)

Plants produce diverse flavonoids for defense and stress resistance, most of which have health benefits and are widely used as food additives and medicines. Methylation of the free hydroxyl groups of flavonoids, catalyzed by S -adenosyl-l-methionine-dependent O-methyltransferases (OMTs), significantly affects their physicochemical properties and bioactivities. Soybeans ( Glycine max ) contain a rich pool of O-methylated flavonoids. However, the OMTs responsible for flavonoid methylation in G. max remain largely unknown. We screened the G. max genome and obtained 22 putative OMT-encoding genes that share a broad spectrum of amino acid identities (25-96%); among them, 19 OMTs were successfully cloned and heterologously expressed in Escherichia coli . We used the flavonoids containing the free 3, 5, 7, 8, 3', 4' hydroxyl group, such as flavones (luteolin and 7, 8-dihydroxyflavone), flavonols (kaempferol and quercetin), flavanones (naringenin and eriodictyol), isoflavonoids (daidzein and glycetein), and caffeic acid as substrates, and 15 OMTs were proven to catalyze at least one substrate. The methylation activities of these GmOMTs covered the 3, 7, 8, 3', 4'- hydroxyl of flavonoids and 7, 4'- hydroxyl of isoflavonoids. The systematic characterization of G . max flavonoid OMTs provides insights into the biosynthesis of methylated flavonoids in soybeans and OMT bioparts for the production of methylated flavonoids via synthetic biology., Competing Interests: The authors have no interests to declare., (© 2024 The Authors.)

Silicosis is a chronic illness marked by diffuse fibrosis in lung tissue resulting from continuous exposure to SiO 2 -rich dust in the workplace. The onset and progression of silicosis is a complicated and poorly understood pathological process involving numerous cells and molecules. However, silicosis poses a severe threat to public health in developing countries, where it is the most prevalent occupational disease. There is convincing evidence supporting that innate and adaptive immune cells, as well as their cytokines, play a significant role in the development of silicosis. In this review, we describe the roles of immune cells and cytokines in silicosis, and summarize current knowledge on several important inflammatory signaling pathways associated with the disease, aiming to provide novel targets and strategies for the treatment of silicosis-related inflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liu, Sun, Han, Zhan and Jiang.)

Taihu Lake has suffered from eutrophication and algal blooms for decades, primarily due to increasing anthropogenic pollutants from human activities. Extensive research and widespread implementation of water pollution control measures have significantly contributed to the improvement of water quality of Taihu Lake. However, the relevant experience of Taihu Lake pollution control has not been well summarized to provide insight for future lake restoration. This review article seeks to address this gap by first providing a comprehensive overview of Taihu Lake's water quality dynamics over the past thirty years, characterized by two distinct stages: (I) water quality deterioration (1990s-2007); and (II) water total nitrogen (TN) improvement but total phosphorus (TP) fluctuation (2007-current). Subsequently, we conducted a thorough review of the experiences and challenges associated with water pollution control during these two stages. Generally, pollution control practices emphasized point source control but overlooked non-point sources before 2007, possibly due to point sources being easier to identify and manage. Accordingly, the focus shifted from industrial point sources to a combination of industrial point and agricultural non-point sources after 2007 to control water pollution in the Taihu Lake Basin. Numerous studies have delved into non-point source pollution control, including source control, transport intercept, in-lake measures, and the integration of these technologies. Taken together, this paper provides suggestions based on the needs and opportunities of this region. Further research is needed to better understand and model the underlying pollution processes, as well as to increase public participation and improve policy and law implementation, which will assist decision-makers in formulating better water management in Taihu Lake., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Improving the adsorption performance of wetland fillers is of great significance for enhancing pollutant removal in constructed wetlands. Currently, limited by complex preparation processes and high costs, large numbers of high adsorption fillers studied in lab are difficult to be applied in practical engineering. In this study, a newly low-cost and efficient phosphorus removal composite wetland filler (CFB) is prepared by using industrial and agriculture waste (steel slag and oyster shells) and natural ore (volcanic rock) as raw materials. The results show that phosphorus removal efficiency was largely enhanced by synergistic effects of steel slag, oyster shells, and volcanic rock, and it was mainly influenced by the proportion of each component of CFB. Based on the fitting of the classical isothermal equation, the adsorption capacity of CFB is 18.339 mg/g. The adsorption of phosphorus by CFB is endothermic and spontaneous, and there are heterogeneous surfaces and multi-layer adsorption processes, as well as pH value and temperature, are free from the influence on CFB phosphorus removal. During the practical wastewater application experiments, the phosphorus removal rate of the CFB-filled constructed wetland apparatus (CW-A) can reach 94.89% and is free from the influence on the removal of other pollutants (COD, TN, and NH 3 -N) by the system. Overall, the prepared CFB is of excellent decontamination effect, an extremely simple preparation process, low cost, and sound practical engineering application potential, providing new ideas and approaches for enhancing the phosphorus removal capacity and waste resource utilization of constructed wetland systems., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The clinical implications of extrachromosomal DNA (ecDNA) in cancer therapy remain largely elusive. Here, we present a comprehensive analysis of ecDNA amplification spectra and their association with clinical and molecular features in multiple cohorts comprising over 13,000 pan-cancer patients. Using our developed computational framework, GCAP, and validating it with multifaceted approaches, we reveal a consistent pan-cancer pattern of mutual exclusivity between ecDNA amplification and microsatellite instability (MSI). In addition, we establish the role of ecDNA amplification as a risk factor and refine genomic subtypes in a cohort from 1015 colorectal cancer patients. Importantly, our investigation incorporates data from four clinical trials focused on anti-PD-1 immunotherapy, demonstrating the pivotal role of ecDNA amplification as a biomarker for guiding checkpoint blockade immunotherapy in gastrointestinal cancer. This finding represents clinical evidence linking ecDNA amplification to the effectiveness of immunotherapeutic interventions. Overall, our study provides a proof-of-concept of identifying ecDNA amplification from cancer whole-exome sequencing (WES) data, highlighting the potential of ecDNA amplification as a valuable biomarker for facilitating personalized cancer treatment., (© 2024. The Author(s).)

Aim: To explore the brain mechanism of acupuncture for children with anisometropic amblyopia using the voxel-mirror homotopic connectivity (VMHC) analysis method of resting functional magnetic resonance imaging (rs-fMRI) technology based on clinical effectiveness., Methods: Eighty children with anisometropic monocular amblyopia were randomly divided into two groups: control (40 cases, 1 case of shedding) and acupuncture (40 cases, 1 case of shedding) groups. The control group was treated with glasses, red flash, grating, and visual stimulations, with each procedure conducted for 5min per time. Based on routine treatment, the acupuncture group underwent acupuncture of "regulating qi and unblocking meridians to bright eyes", Jingming (BL1), Cuanzhu (BL2), Guangming (GB37), Fengchi (GB20) acupoints were taken on both sides, with the needle kept for 30min each time. Both groups were treated once every other day, three times per week, for a total of 4wk. After the treatment, the overall curative effect of the two groups and the latency and amplitude changes of P100 wave of pattern visual-evoked potential were counted. At the same time, nine children with left eye amblyopia were randomly selected from the two groups and were scanned with rs-fMRI before and after treatment. The differences in the brain regions between the two groups were compared and analyzed with VMHC., Results: Chi-square test showed a notable difference in the total efficiency rate between the acupuncture (94.87%) and control groups (79.49%). Regarding the P100 wave latency and amplitude, the acupuncture group had significantly shorter latency and higher amplitude of P100 wave than the control group. Moreover, the VMHC values of the bilateral temporal lobe, superior temporal gyrus, and middle temporal gyrus were notably increased in the acupuncture group after treatment., Conclusion: Acupuncture combined with conventional treatment can significantly improve the corrected visual acuity and optic nerve conduction in children with anisometropic amblyopia. Compared with the conventional treatment, the regulation of acupuncture on the functional activities of the relevant brain areas in the anterior cerebellum may be an effective acupuncture mechanism for anisometropic amblyopia., Competing Interests: Conflicts of Interest: Wang J, None; Jia J, None; Sun Y, None; Ma CB, None; Chen YZ, None; Liu AG, None; Yan XK, None., (International Journal of Ophthalmology Press.)

Lactobacillus species have been shown to alleviate gut inflammation and oxidative stress. However, the effect of different lactobacilli components on gut inflammation has not been well studied. This study aims to identify the differences in the effect and mechanisms of different forms and components of Limosilactobacillus mucosae (LM) treatment in the alleviation of gut inflammation using a colitis mouse model that is induced by dextran sodium sulfate (DSS). Seventy-two C57BL/6 mice were divided into six groups: control, DSS, live LM+DSS (LM+DSS), heat-killed LM+DSS (HKLM+DSS), LM cell-free supernatant + DSS (LMCS+DSS), and MRS medium + DSS (MRS+DSS). The mice were treated with different forms and components of LM for two weeks before DSS treatment. After that, the mice were sacrificed for an assessment of their levels of inflammatory cytokines, serotonin (5-HT) receptors (HTRs), and tryptophan metabolites. The results showed that, compared to other treatments, LMCS was more effective ( p < 0.05) in the alleviation of DSS-induced body weight loss and led to an increase in the disease activity index score. All three forms and components of LM increased ( p < 0.05) the levels of indole-3-acetic acid but reduced ( p < 0.05) the levels of 5-HT in the colon. HKLM or LMCS reduced ( p < 0.05) the percentages of CD3 + CD8 + cytotoxic T cells but increased ( p < 0.05) the percentages of CD3 + CD4 + T helper cells in the spleen. LM or HKLM increased ( p < 0.05) abundances of CD4 + Foxp3 + regulatory T cells in the spleen. The LM and LMCS treatments reduced ( p < 0.05) the expression of the pro-inflammatory cytokines Il6 and Il17a . The mice in the HKLM+DSS group had higher ( p < 0.05) mRNA levels of the anti-inflammatory cytokine Il10 , the cell differentiation and proliferation markers Lgr5 and Ki67 , the 5-HT degradation enzyme Maoa , and HTRs ( Htr1a , Htr2a , and Htr2b ) in the colon. All three forms and components of LM reduced the phosphorylation of STAT3. The above findings can help to optimize the functionality of probiotics and develop new dietary strategies that aid in the maintenance of a healthy gut.

Diterpenoid tanshinones (DTs) are a bioactive fraction extracted from Salvia miltiorrhiza . High-performance liquid chromatography analysis revealed the presence of four compounds, namely, tanshinone IIA, tanshinone I, cryptotanshinone, and dihydrotanshinone. In this study, we aimed to propose a possible mechanism for the anti-lung cancer effect of DT. To do so, we utilized a lung cancer nude mice model and a lung cancer cell line (PC9) to investigate the effect of DT on lung cancer. We employed immunohistochemistry, enzyme-linked immunosorbent assay, hematoxylin and eosin staining, and immunofluorescence to analyze the pharmacological role of DT in the inhibition of lung cancer growth. The results showed that DT inhibited tumor growth, induced apoptosis in the nude mice model, and reduced inflammatory cell infiltration. Additionally, DT inhibited PC9 lung cancer cells, growth, proliferation, and migration. The mechanism of action of DT involves not only directly inhibiting cell proliferation and migration but also improving the tumor microenvironment. DT significantly increased the expression of important intestinal gap junction proteins, such as zonula occludens 1 (ZO-1) and occludin I. This upregulation contributes to the reinforcement of the intestinal mucosal barrier, thereby reducing the paracellular transport of lipopolysaccharides (LPS) through the intestine. Consequently, the decreased LPS levels lead to the inhibition of NF-κB expression and downregulation of macrophage polarization, as indicated by the decreased expression of CD68. In conclusion, this study has confirmed that DT has anti-lung cancer properties by improving the inflammatory tumor microenvironment via regulating macrophage polarization and inhibiting LPS-associated immune response. These results provide new insights into the mechanism of DT action against lung cancer., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)

As surface ozone (O 3 ) gains increasing attention, there is an urgent need for high temporal resolution and accurate O 3 monitoring. By taking advantage of the progress in artificial intelligence, deep learning models have been applied to satellite based O 3 retrieval. However, the underlying physical mechanisms that influence surface O 3 into model construction have rarely been considered. To overcome this issue, we considered the physical mechanisms influencing surface O 3 and used them to select relevant variable features for developing a novel deep learning model. We used a wide and deep model architecture to account for linear and non-linear relationships between the variables and surface O 3 . Using the developed model, we performed hourly inversions of surface O 3 retrieval over China from 2017 to 2019 (9:00-17:00, local time). The validation results based on sample-based (site-based) methods yielded an R 2 of 0.94 (0.86) and an RMSE of 12.79 (19.13) μg/m 3 , indicating the accuracy of the models. The average surface O 3 concentrations in China in 2017, 2018, and 2019 were 82, 78, and 87 μg/m 3 , respectively. There was a diurnal pattern in surface O 3 in China, with levels rising significantly from 55 μg/m 3 at 9:00 a.m. to 96 μg/m 3 at 15:00. Between 15:00 and 16:00, the O 3 concentration remained stable at 95 μg/m 3 and decreased slightly thereafter (16:00-17:00). The results of this study contribute to a deeper understanding of the physical mechanisms of ozone and facilitate further studies on ozone monitoring, thereby enhancing our understanding of the spatiotemporal characteristics of ozone., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Soil organic carbon (SOC) is the core component of terrestrial carbon (C) sink. Exploring the transformation and stabilization mechanism of SOC is key to understand the function of terrestrial C sink which copes with climate change. The traditional perspective is that plant residues are the initial source of SOC. The new concept of "soil microbial C pump" emphasizes that the synthesized products of soil microbial assimilation are important contributors to the stable SOC. This provides a new insight to the sequestration mechanism of SOC. Due to the complex and variable decomposition process of plant residues and the high heterogeneity of microbial residues, the transformation and stabilization mechanism of plant residues and microbial residues into SOC is still unclear. We reviewed research progress in plant and microbial residues, and introduced the characterization methods of quantification and transformation of plant residues and microbial residues, and also summarized the new findings on the transformation of plant and microbial residues into SOC. We further discussed the contribution and driving factors of microbial and plant-derived C to SOC. Finally, we prospected the future development direction and research focus in this field. This review would provide the scientific reference for the research of soil C sequestration in terrestrial ecosystem.

Silybin (SIL) is a versatile bioactive compound used for improving liver damage and lipid disorders and is also thought to be beneficial for atherosclerosis (AS). The goal of this study was to investigate the efficacy of SIL in the treatment of AS in ApoE -/- mice fed a high-fat diet and explore the mechanism underlying treatment outcomes. We found that SIL significantly alleviated AS-related parameters, including the extent of aortic plaque formation, hyperlipidemia, and adhesion molecule secretion in the vascular endothelium. 16 S rRNA gene sequencing analysis, together with the application of antibiotics, showed that intestinal butyrate-producing bacteria mediated the ameliorative effect of SIL on AS. Further analysis revealed that SIL facilitated butyrate production by increasing the level of butyryl-CoA: acetate CoA-transferase (BUT). The increased expression of monocarboxylic acid transporter-1 (MCT1) induced by butyrate and MCT4 induced by SIL in the apical and basolateral membranes of colonocytes, respectively, resulted in enhanced absorption of intestinal butyrate into the circulation, leading to the alleviation of arterial endothelium dysfunction. Moreover, the SIL-mediated increase in intestinal butyrate levels restored gut integrity by upregulating the expression of tight junction proteins and promoting gut immunity, thus inhibiting the AS-induced inflammatory response. This is the first study to show that SIL can alleviate AS by modulating the production of bacterial butyrate and its subsequent absorption., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

To improve the uncertainty quantification of variance networks, we propose a novel tree-structured local neural network model that partitions the feature space into multiple regions based on uncertainty heterogeneity. A tree is built upon giving the training data, whose leaf nodes represent different regions where region-specific neural networks are trained to predict both the mean and the variance for quantifying uncertainty. The proposed uncertainty-splitting neural regression tree (USNRT) employs novel splitting criteria. At each node, a neural network is trained on the full data first, and a statistical test for the residuals is conducted to find the best split, corresponding to the two subregions with the most significant uncertainty heterogeneity between them. USNRT is computationally friendly, because very few leaf nodes are sufficient and pruning is unnecessary. Furthermore, an ensemble version can be easily constructed to estimate the total uncertainty, including the aleatory and epistemic. On extensive UCI datasets, USNRT or its ensemble shows superior performance compared to some recent popular methods for quantifying uncertainty with variances. Through comprehensive visualization and analysis, we uncover how USNRT works and show its merits, revealing that uncertainty heterogeneity does exist in many datasets and can be learned by USNRT.

Microbial extracellular respiration is an important energy metabolism on earth, which is significant for the elemental biogeochemical cycle. Herein, extracellular Fe(III) and electrode respiration were confirmed in Thermoanaerobacterium thermosaccharolyticum MJ2. The intra/extracellular electron transfer (IET/EET) mechanism of MJ2 was investigated by comparative genomic analysis for the first time. Morphological characterization and electrochemical properties of anode illustrated that MJ2 generated bio-electricity by forming a biofilm. The respiration chain inhibition and enzyme activity tests showed that hydrogenase with cytochrome c (Cyt-c) was involved in IET of MJ2. Noteworthily, the exogenous Cyt-c increased hydrogenase activity to promote bio-electricity generation by 92.84 %. The Cyt-c gene synteny between MJ2 and another well-known exoelectrogen (Thermincola potens JR) indicated that Cyt-c bound to the outer membrane mediated the formation of biofilm involved in EET of MJ2. This study broadened the understanding of microbial extracellular respiration diversity and provided new insights to explore the electron transfer pathways of exoelectrogens., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objectives: To analyze the effect of acupuncture at the acupoints for Yizhi Tiaoshen (benefiting the intelligence and regulating the spirit) on the functional connectivity between the hippocampus and the whole brain in the patients with Alzheimer's disease (AD), and reveal the brain function mechanism of acupuncture in treatment of AD using resting state functional magnetic resonance imaging (rs-fMRI)., Methods: Sixty patients with mild to moderate AD were randomly divided into an acupuncture + medication group (30 cases, 3 cases dropped out) and a western medication group (30 cases, 2 cases dropped out). In the western medication group, the donepezil hydrochloride tablets were administered orally, 2.5 mg to 5 mg each time, once daily; and adjusted to be 10 mg each time after 4 weeks of medication. Besides the therapy as the western medication group, in the acupuncture + medication group, acupuncture was supplemented at the acupoints for Yizhi Tiaoshen , i.e. Baihui (GV 20), Sishencong (EX-HN 1), and bilateral Shenmen (HT 7), Neiguan (PC 6), Zusanli (ST 36), Sanyinjiao (SP 6) and Xuanzhong (GB 39). The needles were retained for 30 min in one treatment, once daily; and 6 treatments were required weekly. The duration of treatment was 6 weeks in each group. The general cognitive function was assessed by the mini-mental state examination (MMSE) and Alzheimer's disease assessment scale-cognitive part (ADAS-Cog) before and after treatment in the two groups. Using the rs-fMRI, the changes in the functional connectivity (FC) of the left hippocampus and the whole brain before and after treatment were analyzed in the patients of the two groups (11 cases in the acupuncture + medication group and 12 cases in the western medication group)., Results: After treatment, compared with those before treatment, MMSE scores increased and ADAS-Cog scores decreased in the two groups ( P< 0.05); MMSE score was higher, while the ADAS-Cog score was lower in the acupuncture + medication group when compared with those in the western medication group ( P ≤0.05). After treatment, in the western medication group, FC of the left hippocampus was enhanced with the left fusiform gyrus, the inferior frontal gyrus of the left triangular region, the bilateral superior temporal gyrus and the right superior parietal gyrus ( P <0.05), while FC was weakened with the left inferior temporal gyrus, the left middle frontal gyrus and the right dorsolateral superior frontal gyrus when compared with that before treatment ( P< 0.05). After treatment, in the acupuncture + medication group, FC of the left hippocampus was increased with the right gyrus rectus, the left inferior occipital gyrus, the right superior temporal gyrus and the left middle occipital gyrus ( P< 0.05), and it was declined with the left thalamus ( P< 0.05) when compared with those before treatment. After treatment, in the acupuncture + medication group, FC of the left hippocampus was strengthened with the bilateral inferior temporal gyrus, the bilateral middle temporal gyrus, the right gyrus rectus, the bilateral superior occipital gyrus, the left lenticular nucleus putamen, the left calcarine fissure and surrounding cortex, the inferior frontal gyrus of the left insulae operculum, the left medial superior frontal gyrus and the right posterior central gyrus ( P <0.05) compared with that of the western medication group., Conclusions: Acupuncture at the acupoints for Yizhi Tiaoshen improves the cognitive function of AD patients, and its main brain functional mechanism is related to intensifying the functional connectivity of the left hippocampus with the default network (inferior temporal gyrus, middle temporal gyrus and superior frontal gyrus, gyrus rectus), as well as with the sensory (posterior central gyrus) and visual (calcarine fissure and surrounding cortex and superior occipital gyrus) brain regions.

Coarse-mode aerosol optical depths (cAODs) are critical for understanding the impact of coarse particle sizes, especially dust aerosols, on climate. Currently, the limited data length and high uncertainty of satellite products diminish the applicability of cAOD for climate research. Here, we propose a spatiotemporal coaction deep-learning model (SCAM) for the retrieval of global land cAOD (500 nm) from 2001-2021. In contrast to conventional deep-learning models, the SCAM considers the impacts of spatiotemporal feature interactions and can simultaneously describe linear and nonlinear relationships for retrievals. Based on these unique characteristics, the SCAM considerably improved global daily cAOD accuracies and coverages (R = 0.82, root-mean-square error [RMSE] = 0.04). Compared to official products from the multiangle imaging spectroradiometer (MISR), the moderate resolution imaging spectroradiometer (MODIS), and the polarization and directionality of Earth's reflectances (POLDER) instrument, as well as the physical-deep learning (Phy-DL) derived cAOD, the SCAM cAOD improved the monthly R from 0.44 to 0.88 and more accurately captured over the desert regions. Based on the SCAM cAOD, daily dust cases decreased over the Sahara, Thar Desert, Gobi Desert, and Middle East during 2001-2021 (>3 × 10 -3 /year). The SCAM-retrieved cAOD can contribute considerably to resolving the climate change uncertainty related to coarse-mode aerosols. Our proposed method is highly valuable for reducing uncertainties regarding coarse aerosols and climate interactions.

Background: Circulating tumor DNA (ctDNA) is a promising biomarker for predicting relapse in multiple solid cancers. However, the predictive value of ctDNA for disease recurrence remains indefinite in locoregional gastric cancer (GC). Here, we aimed to evaluate the predictive value of ctDNA in this context., Methods: From 2016 to 2019, 100 patients with stage II/III resectable GC were recruited in this prospective cohort study (NCT02887612). Primary tumors were collected during surgical resection, and plasma samples were collected perioperatively and within 3 months after adjuvant chemotherapy (ACT). Somatic variants were captured via a targeted sequencing panel of 425 cancer-related genes. The plasma was defined as ctDNA-positive only if one or more variants detected in the plasma were presented in at least 2% of the primary tumors., Results: Compared with ctDNA-negative patients, patients with positive postoperative ctDNA had moderately higher risk of recurrence [hazard ratio (HR) = 2.74, 95% confidence interval (CI) = 1.37-5.48; P = 0.003], while patients with positive post-ACT ctDNA showed remarkably higher risk (HR = 14.99, 95% CI = 3.08-72.96; P < 0.001). Multivariate analyses indicated that both postoperative and post-ACT ctDNA positivity were independent predictors of recurrence-free survival (RFS). Moreover, post-ACT ctDNA achieved better predictive performance (sensitivity, 77.8%; specificity, 90.6%) than both postoperative ctDNA and serial cancer antigen. A comprehensive model incorporating ctDNA for recurrence risk prediction showed a higher C-index (0.78; 95% CI = 0.71-0.84) than the model without ctDNA (0.71; 95% CI = 0.64-0.79; P = 0.009)., Conclusions: Residual ctDNA after ACT effectively predicts high recurrence risk in stage II/III GC, and the combination of tissue-based and circulating tumor features could achieve better risk prediction., (© 2023 The Authors. Cancer Communications published by John Wiley & Sons Australia, Ltd on behalf of SUN YAT-SEN UNIVERSITY CANCER CENTER.)

Green micro-light emitting diodes (micro-LEDs) is one of the three primary color light sources as full-color display, which serves as a key research object in the field of micro-LED display. As the micro-LED size decreases, the surface-area-to-volume ratio of the device increases, leading to more serious damage on the sidewall by inductively coupled plasma (ICP) etching. The passivation process of SiO 2 provides an effective method to reduce sidewall damage caused by ICP etching. In this work, green rectangular micro-LEDs with passivation layer thickness of 0∼600 nm was designed using the finite-difference time-domain (FDTD) simulation. In order to verify the simulation results, the micro-LED array was fabricated by parallel laser micro-lens array (MLA) lithography in high speed and large area. The effect of the SiO 2 passivation layer thickness on the performance of the green micro-LED was analyzed, which shows that the passivation layer thickness-light extraction efficiency curve fluctuates periodically. For the sample with 90 nm thickness of SiO 2 passivation layer, there exists a small leakage current and higher operating current density, and the maximum external quantum efficiency (EQE) is 2.8 times higher than micro-LED without SiO 2 passivation layer.

To investigate the variations of PM 2.5 and O 3 and their synergistic effects with influencing factors at different time scales, we employed Bayesian estimator of abrupt seasonal and trend change to analyze the nonlinear variation process of PM 2.5 and O 3 . Wavelet coherence and multiple wavelet coherence were utilized to quantify the coupling oscillation relationships of PM 2.5 and O 3 on single/multiple meteorological factors in the time-frequency domain. Furthermore, we combined this analysis with the partial wavelet coherence to quantitatively evaluate the influence of atmospheric teleconnection factors on the response relationships. The results obtained from this comprehensive analysis are as follows: (1) The seasonal component of PM 2.5 exhibited a change point, which was most likely to occur in January 2017. The trend component showed a discontinuous decline and had a change point, which was most likely to appear in February 2017. The seasonal component of O 3 did not exhibit a change point, while the trend component showed a discontinuous rise with two change points, which were most likely to occur in July 2018 and May 2017. (2) The phase and coherence relationships of PM 2.5 and O 3 on meteorological factors varied across different time scales. Stable phase relationships were observed on both small- and large-time scales, whereas no stable phase relationship was formed on medium scales. On all-time scales, sunshine duration was the best single variable for explaining PM 2.5 variations and precipitation was the best single variable explaining O 3 variations. When compared to single meteorological factors, the combination of multiple meteorological factors significantly improved the ability to explain variations in PM 2.5 and O 3 on small-time scales. (3) Atmospheric teleconnection factors were important driving factors affecting the response relationships of PM 2.5 and O 3 on meteorological factors and they had greater impact on the relationship at medium-time scales compared to small- and large-time scales., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Leukemia encompasses a group of highly heterogeneous diseases that pose a serious threat to human health. The long-term outcome of patients with leukemia still needs to be improved and new effective therapeutic strategies continue to be an unmet clinical need. Shikonin (SHK) is a naphthoquinone derivative that shows multiple biological function includes anti-tumor, anti-inflammatory, and anti-allergic effects. Numerous studies have reported the anti-leukemia activity of SHK during the last 3 decades and there are studies showing that SHK is particularly effective towards various leukemia cells compared to solid tumors. In this review, we will discuss the anti-leukemia effect of SHK and summarize the underlying mechanisms. Therefore, SHK may be a promising agent to be developed as an anti-leukemia drug., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Dong, Chang, Gao, Zhang, Yan, Wu and Wang.)