The autophagy-lysosome pathway: a potential target in the chemical and gene therapeutic strategies for Parkinson's disease.

Parkinson's disease is a common neurodegenerative disease with movement disorders associated with the intracytoplasmic deposition of aggregate proteins such as α-synuclein in neurons. As one of the major intracellular degradation pathways, the autophagy-lysosome pathway plays an important role in eliminating these proteins. Accumulating evidence has shown that upregulation of the autophagy-lysosome pathway may contribute to the clearance of α-synuclein aggregates and protect against degeneration of dopaminergic neurons in Parkinson's disease. Moreover, multiple genes associated with the pathogenesis of Parkinson's disease are intimately linked to alterations in the autophagy-lysosome pathway. Thus, this pathway appears to be a promising therapeutic target for treatment of Parkinson's disease. In this review, we briefly introduce the machinery of autophagy. Then, we provide a description of the effects of Parkinson's disease-related genes on the autophagy-lysosome pathway. Finally, we highlight the potential chemical and genetic therapeutic strategies targeting the autophagy-lysosome pathway and their applications in Parkinson's disease.

Regulation of neuronal plasticity associated with neuropsychiatric disorders by the orexinergic system.

Orexins are a family of neuropeptides secreted by neurons in the lateral hypothalamus (LH). These peptides act widespreadly across the body by interacting with specific orexin receptors on target cells, which comprise the orexinergic system. Emerging evidence has revealed that the orexinergic system is tightly associated with neuropsychiatric disorders; however, the underlying mechanisms require further exploration. Neuropsychiatric disorders have also been associated with neuroplasticity, while orexins have been shown to play regulatory roles in neuronal plasticity. As such, this review aims to summarize the recent progress of research investigating the roles of the orexinergic system in neuronal plasticity and associated neuropsychiatric disorders, including addiction, depression, and schizophrenia, which may provide novel insights into the mechanism of the orexinergic system in the pathogenesis of these neuropsychiatric disorders.

A semi-mechanistic aging model of Pb added to soil by a modified stable isotope dilution technique.

The aging of Pb added to soils has not been studied by the isotopic technology because of difficulties in determination of isotopically exchangeable Pb in soil, so that a set of 10 typical agricultural soils in China and a one-year aging experiment with the addition of water-soluble Pb to the soils were carried out. A modified stable isotope dilution technique to determine isotopically exchangeable Pb in soil was developed where 0.2 mM EDTA (ethylenediaminetetraacetic acid) as the extractant. When water-soluble Pb was added to soil, the isotopically exchangeable Pb (Eadd%, the percentage of isotopically exchangeable Pb to total Pb added to soil) initially decreased rapidly and gradually slowly. A semi-mechanistic aging model of Pb added to soils, including precipitation/nucleation (Y1), micropore diffusion (Y2), and organic matter encapsulation processes (Y3) was developed with the root mean square error 8.3% where Y1, Y2, and Y3 accounted for 0.02~26.9%, 1.4~21.8% and 3.8~11.3%, respectively, when the pH 4.0~8.0 and organic matter 2.0~6.0%. Soil pH was a vital factor affecting the aging rate. When the pH increased by 1 unit, the Eadd value decreased by approximately 9%. The model could be used to scale ecotoxicological data of Pb in soil generated in different aging times.

Spatiotemporal variations and priority ranking of emerging contaminants in nanwan reservoir: A case study from the agricultural region in huaihe river basin in China.

The presence of emerging contaminants (ECs) in drinking water sources is an increasing concern, yet limited data exists on their occurrence and risk in the upper Huaihe River Basin, an important agricultural region in Central China. This study investigated 70 ECs, including pesticide and antibiotics in surface water from drinking water source areas in Nanwan Reservoir along the upper reaches of the Huaihe River Basin to prioritize the ECs based on ecological risk and health risk assessment. A total of 66 ECs were detected in the surface water at least once at the selected 38 sampling sites, with concentrations ranging from 0.04 to 2508 ng/L. Ecological risk assessment using the risk quotient (RQ) method revealed high risks (RQ > 1) from 7 ECs in the dry season and 15 ECs in the wet season, with triazine pesticides as the main contributors. Non-carcinogenic risks were below negligible levels, but carcinogenic risks from neonicotinoid and carbamate pesticides and macrolide antibiotics were concerning for teenagers. Ciprofloxacin exhibited a high level of resistance risk during the wet season. A multi-indicator prioritization approach integrating occurrence, risk, and chemical property data ranked 6 pesticides and 3 antibiotics as priority pollutants. The results highlight EC contamination of drinking water sources in this agriculturally-intensive region and the need for targeted monitoring and management to protect water quality.

Application and research progress of ARTP mutagenesis in actinomycetes breeding.

Atmospheric and room temperature plasma (ARTP) is an emerging artificial mutagenesis breeding technology. In comparison to traditional physical and chemical methods, ARTP technology can induce DNA damage more effectively and obtain mutation strains with stable heredity more easily after screening. It possesses advantages such as simplicity, safety, non-toxicity, and cost-effectiveness, showing high application value in microbial breeding. This article focuses on ARTP mutagenesis breeding of actinomycetes, specifically highlighting the application of ARTP mutagenesis technology in improving the performance of strains and enhancing the biosynthetic capabilities of actinomycetes. We analyzed the advantages and challenges of ARTP technology in actinomycetes breeding and summarized the common features, specific mutation sites and metabolic pathways of ARTP mutagenic strains, which could give guidance for genetic modification. It suggested that the future research work should focus on the establishment of high throughput rapid screening methods and integrate transcriptomics, proteomics, metabonomics and other omics to delve into the genetic regulations and synthetic mechanisms of the bioactive substances in ARTP mutated actinomycetes. This article aims to provide new perspectives for actinomycetes breeding through the establishment and application of ARTP mutagenesis technology, thereby promoting source innovation and the sustainable industrial development of actinomycetes.

Review of research progress on the production of cellulase from filamentous fungi.

Cellulases have been widely used in many fields such as animal feed, textile, food, lignocellulose bioconversion, etc. Efficient and low-cost production of cellulases is very important for its industrial application, especially in bioconversion of lignocellulosic biomass. Filamentous fungi are currently widely used in industrial cellulase production due to their ability to secrete large amounts of active free cellulases extracellularly. This review comprehensively summarized the research progress on cellulases from filamentous fungi in recent years, including filamentous fungi used for cellulase production and its modification strategies, enzyme compositions, characterization methods and application of fungal cellulase systems, and the production of fungal cellulase includes production processes, factors affecting cellulase production such as inducers, fermentation medium, process parameters and their control strategies. Also, the future perspectives and research topics in fungal cellulase production are presented in the end of the review. The review helps to deepen the understanding of the current status of fungal cellulases, thereby promoting the production technology progress and industrial application of filamentous fungal cellulase.

Visual Feedback Gain Modulates the Activation of Task-Related Networks and the Suppression of Non-Task Networks During Precise Grasping.

Visual feedback gain is a crucial factor influencing the performance of precision grasping tasks, involving multiple brain regions of the visual motor system during task execution. However, the dynamic changes in brain network during this process remain unclear. The aim of this study is to investigate the impact of changes in visual feedback gain during precision grasping on brain network dynamics. Sixteen participants performed precision grip tasks at 15% of MVC under low (0.1°), medium (1°), and high (3°) visual feedback gain conditions, with simultaneous recording of EEG and right-hand precision grip data during the tasks. Utilizing electroencephalogram (EEG) microstate analysis, multiple parameters (Duration, Occurrence, Coverage, Transition probability(TP)) were extracted to assess changes in brain network dynamics. Precision grip accuracy and stability were evaluated using root mean square error(RMSE) and coefficient of variation(CV) of grip force. Compared to low visual feedback gain, under medium/high gain, the Duration, Occurrence, and Coverage of microstates B and D increase, while those of microstates A and C decrease. The Transition probability from microstates A, C, and D to B all increase. Additionally, RMSE and CV of grip force decrease. Occurrence and Coverage of microstates B and C are negatively correlated with RMSE and CV. These findings suggest that visual feedback gain affects the brain network dynamics during precision grasping; moderate increase in visual feedback gain can enhance the accuracy and stability of grip force, whereby the increased Occurrence and Coverage of microstates B and C contribute to improved performance in precision grasping. Our results play a crucial role in better understanding the impact of visual feedback gain on the motor control of precision grasping.

Enhancing mango yield and soil health with organic and slow-release fertilizers: A multifaceted evaluation.

Excessive utilization of chemical fertilizers in mango orchards not only hampers the attainment of sustainable harvests but also poses significant ecological detriments. This investigation proposes a promising solution by advocating the judicious replacement of chemical fertilizers with organic fertilizer (OF) and slow-release fertilizer (SRF), with potential to bolster soil health and augment crop productivity. In light of the promise held by these alternatives, it is imperative to establish detailed fertilization protocols for enhanced sustainable practices in mango farming. This two-year field study employed a comprehensive suite of seven fertilization strategies, unveiling that a 25 % chemical fertilizers substitution with OF and SRF improved mango yields by 12.5 % and 11.3 %, respectively, over standard practices. Additionally, these approaches substantially augmented the nutritional quality of mangoes, evident from Vitamin C enhancements of 53.9 % to 56.9 %, and improvements in sugar-to-acid ratio (19.2 %-30.3 %) and solid-to-acid ratio (12.1 %-25.3 %). Notably, the application of OF and SRF led to increased leaf nitrogen and phosphorus concentrations, while simultaneously reducing soil phosphorus and potassium levels. Furthermore, these fertilizers fostered the growth of beneficial soil microorganisms, namely Actinobacteria and Proteobacteria, and strengthened the synergy within the soil bacterial community, hence optimizing bacterial competition and nutrient cycling. The study proposes that the adoption of OF or SRF can effectively regulate soil nutrient balance, promote resilient and functional soil bacterial ecosystems, and ultimately improve mango yield and fruit quality. It recommends a fertilization scheme incorporating 25 % organic or slow-release nitrogen to align with ecological sustainability goals, promoting a more vigorous and resilient soil and crop system.

Ultrastrong, flexible thermogalvanic armor with a Carnot-relative efficiency over 8.

Body heat, a clean and ubiquitous energy source, is promising as a renewable resource to supply wearable electronics. Emerging tough thermogalvanic device could be a sustainable platform to convert body heat energy into electricity for powering wearable electronics if its Carnot-relative efficiency (ηr) reaches ~5%. However, maximizing both the ηr and mechanical strength of the device are mutually exclusive. Here, we develop a rational strategy to construct a flexible thermogalvanic armor (FTGA) with a ηr over 8% near room temperature, yet preserving mechanical robustness. The key to our design lies in simultaneously realizing the thermosensitive-crystallization and salting-out effect in the elaborately designed ion-transport highway to boost ηr and improve mechanical strength. The FTGA achieves an ultrahigh ηr of 8.53%, coupling with impressive mechanical toughness of 70.65 MJ m-3 and substantial elongation (~900%) together. Our strategy holds sustainable potential for harvesting body heat and powering wearable electronics without recharging.

Mo-Doped LaFeO3 Gas Sensors with Enhanced Sensing Performance for Triethylamine Gas.

Triethylamine is a common volatile organic compound (VOC) that plays an important role in areas such as organic solvents, chemical industries, dyestuffs, and leather treatments. However, exposure to triethylamine atmosphere can pose a serious threat to human health. In this study, gas-sensing semiconductor materials of LaFeO3 nano materials with different Mo-doping ratios were synthesized by the sol-gel method. The crystal structures, micro morphologies, and surface states of the prepared samples were characterized by XRD, SEM, and XPS, respectively. The gas-sensing tests showed that the Mo doping enhanced the gas-sensing performance of LaFeO3. Especially, the 4% Mo-doped LaFeO3 exhibited the highest response towards triethylamine (TEA) gas, a value approximately 11 times greater than that of pure LaFeO3. Meantime, the 4% Mo-doped LaFeO3 sensor showed a remarkably robust linear correlation between the response and the concentration (R2 = 0.99736). In addition, the selectivity, stability, response/recovery time, and moisture-proof properties were evaluated. Finally, the gas-sensing mechanism is discussed. This study provides an idea for exploring a new type of efficient and low-cost metal-doped LaFeO3 sensor to monitor the concentration of triethylamine gas for the purpose of safeguarding human health and safety.

A Simplified Analytical Model for Strip Buckling in the Pressure-Assisted Milling Process.

A simplified column-buckling model is developed to understand the buckling mechanism of thin-walled strips restrained by uniform lateral pressure in the milling process. The strip is simplified as two rigid columns connected by a rotation spring, resting on a smooth surface, restrained by a uniform pressure and loaded by an axial force. Two loading cases are considered, i.e., the dead load and the follower load. Analytical solutions for the post-buckling responses of the two cases are derived based on the energy method. The minimum buckling force, Maxwell force and stability conditions for the two cases are established. It is demonstrated that the application of higher uniform pressure increases the minimum buckling force for the column and thus makes the column less likely to buckle. For the same pressure level, the dead load is found to be more effective than the follower load in suppressing the buckling of the system. The effect of initial geometric imperfection is also investigated, and the imperfection amplitude and critical restraining pressure that prevent buckling are found to be linearly related. The analytical results are validated by finite element simulations. This analytical model reveals the buckling mechanism of strips under lateral pressure restraint, which cannot be explained by the conventional bifurcation buckling theory, and provides a theoretical foundation for buckling-prevention strategies during the milling process of thin-walled strips, plates and shells commonly encountered in aerospace or automotive industries.

Mechanical Properties and Microanalytical Study of Concrete Reinforced with Blended Corn Straw and Scrap Steel Fibers.

Fiber concrete exhibits superior performance in various aspects compared to plain concrete and has been widely researched and applied worldwide. However, many industrially made fibers are expensive, and their cost has to be considered before use; thus, it would be economically valuable to find inexpensive fibers with excellent properties to make fiber concrete. Rural areas have many rich straw resources to be disposed of; at the same time, the rapid development of the automobile industry has introduced a large number of used tires containing steel wire with a very low reuse rate. These two low-cost materials can be processed to make fibers, making the study of mechanical properties regarding their incorporation into concrete practically significant for reducing the cost of fiber concrete. Based on this, a three-factor, three-level orthogonal test was conducted to investigate the effects of different dosages of corn straw fibers and scrap steel fibers, as well as the water-cement ratio, on the mechanical properties of concrete. The optimum level of each factor for blended straw-waste-steel-fiber concrete with different mechanical properties was obtained using the polar and ANOVA methods. It was found that the compressive strength, splitting tensile strength, flexural strength, and impact resistance of the specimens after fiber dosing were better than those of plain concrete specimens with the same water-cement ratio. The maximum improvement was 14.96% in cubic compressive strength, 42.90% in tensile strength, and 16.30% in flexural strength, while the maximum improvement in impact energy consumption at the final crack was 228.03%. Combined with SEM microanalysis, the two fibers formed a stronger whole with the C-S-H gel. When the specimen was subjected to load, the two fibers were able to withstand part of the load, thus enhancing the load-bearing capacity. Finally, the optimal mix ratio of blended straw-scrap-steel-fiber concrete was determined to be 0.8% corn straw fibers by volume, 0.6% scrap steel fibers by volume, and a 0.45 water-cement ratio by combining the weights of the levels of each factor under its four different mechanical properties through hierarchical analysis. This analysis of mechanical properties provides a reference for practical applications in future projects.

Embedding Single Pd Atoms on NiGa Intermetallic Surfaces for Efficient and Selective Alkyne Semi-hydrogenation.

Catalytic removal of alkynes is essential in industry for producing polymer-grade alkenes from steam cracking processes. Non-noble Ni-based catalysts hold promise as effective alternatives to industrial Pd-based catalysts but suffer from low activity. Here we report embedding of single-atom Pd onto the NiGa intermetallic surface with replacing Ga atoms via a well-defined synthesis strategy to design Pd1-NiGa catalyst for alkyne semi-hydrogenation. The fabricated Pd1Ni2Ga1 ensemble sites deliver remarkably higher specific mass activity under superb alkene selectivity of >96% than the state-of-the-art catalysts under industry-relevant conditions. Integrated experimental and computational studies reveal that the single-atom Pd located synergizes with the neighbouring Ni sites to facilitate the σ-adsorption of alkyne and dissociation of hydrogen while suppress the alkene adsorption. Such synergistic effects confer the single-atom Pd on the NiGa intermetallic with a Midas touch for alkyne semi-hydrogenation, providing an effective strategy for stimulating low active Ni-based catalysts for other selective hydrogenations in industry.

Exploring the seasonality and optimal control strategy of HIV/AIDS epidemic in China: The impact of seasonal testing.

In this work, we investigate how the seasonal variation in the number of individuals who are tested for an HIV antibody in outpatient clinics affects the HIV transmission patterns in China, which has not been well studied. Based on the characteristics of outpatient testing data and reported cases, we establish a periodic infectious disease model to study the impact of seasonal testing on HIV transmission. The results indicate that the seasonal testing is a driving factor for the seasonality of new cases. We demonstrate the feasibility of ending the HIV/AIDS epidemic. We find that the diagnostic rates related to testing play a crucial role in controlling the size of the epidemic. Specifically, when considering minimizing both infected individuals and diagnostic rates, the level of attention paid to undiagnosed infected individuals is always positively correlated with the optimal diagnostic rates, while the optimal diagnostic rates are negatively correlated with the size of the epidemic at the terminal time.

Effect and mechanism of Qingre Huashi decoction on drug-resistant Helicobacter pylori.

BACKGROUND: Helicobacter pylori (HP), the most common pathogenic microorganism in the stomach, can induce inflammatory reactions in the gastric mucosa, causing chronic gastritis and even gastric cancer. HP infection affects over 4.4 billion people globally, with a worldwide infection rate of up to 50%. The multidrug resistance of HP poses a serious challenge to eradication. It has been de-monstrated that compared to bismuth quadruple therapy, Qingre Huashi decoction (QHD) combined with triple therapy exhibits comparable eradication rates but with a lower incidence of adverse reactions; in addition, QHD can directly inhibit and kill HP in vitro. AIM: To explore the effect and mechanism of QHD on clinically multidrug-resistant and strong biofilm-forming HP. METHODS: In this study, 12 HP strains were isolated in vitro after biopsy during gastroscopy of HP-infected patients. In vitro, the minimum inhibitory concentration (MIC) values for clinical HP strains and biofilm quantification were determined through the E-test method and crystal violet staining, respectively. The most robust biofilm-forming strain of HP was selected, and QHD was evaluated for its inhibitory and bactericidal effects on the strain with strong biofilm formation. This assessment was performed using agar dilution, E-test, killing dynamics, and transmission electron microscopy (TEM). The study also explored the impact of QHD on antibiotic resistance in these HP strains with strong biofilm formation. Crystalline violet method, scanning electron microscopy, laser confocal scanning microscopy, and (p)ppGpp chromatographic identification were employed to evaluate the effect of QHD on biofilm in strong biofilm-forming HP strains. The effect of QHD on biofilm and efflux pump-related gene expression was evaluated by quantitative polymerase chain reaction. Non-targeted metabolomics with UHPLC-MS/MS was used to identify potential metabolic pathways and biomarkers which were different between the NC and QHD groups. RESULTS: HP could form biofilms of different degrees in vitro, and the intensity of formation was associated with the drug resistance of the strain. QHD had strong bacteriostatic and bactericidal effects on HP, with MICs of 32-64 mg/mL. QHD could inhibit the biofilm formation of the strong biofilm-forming HP strains, disrupt the biofilm structure, lower the accumulation of (p)ppGpp, decrease the expression of biofilm-related genes including LuxS, Spot, glup (HP1174), NapA, and CagE, and reduce the expression of efflux pump-related genes such as HP0605, HP0971, HP1327, and HP1489. Based on metabolomic analysis, QHD induced oxidative stress in HP, enhanced metabolism, and potentially inhibited relevant signaling pathways by upregulating adenosine monophosphate (AMP), thereby affecting HP growth, metabolism, and protein synthesis. CONCLUSION: QHD exerts bacteriostatic and bactericidal effects on HP, and reduces HP drug resistance by inhibiting HP biofilm formation, destroying its biofilm structure, inhibiting the expression of biofilm-related genes and efflux pump-related genes, enhancing HP metabolism, and activating AMP in HP.

Temporal insights into molecular and cellular responses during rAAV production in HEK293T cells.

The gene therapy field seeks cost-effective, large-scale production of recombinant adeno-associated virus (rAAV) vectors for high-dosage therapeutic applications. Although strategies like suspension cell culture and transfection optimization have shown moderate success, challenges persist for large-scale applications. To unravel molecular and cellular mechanisms influencing rAAV production, we conducted an SWATH-MS proteomic analysis of HEK293T cells transfected using standard, sub-optimal, and optimal conditions. Gene Ontology and pathway analysis revealed significant protein expression variations, particularly in processes related to cellular homeostasis, metabolic regulation, vesicular transport, ribosomal biogenesis, and cellular proliferation under optimal transfection conditions. This resulted in a 50% increase in rAAV titer compared with the standard protocol. Additionally, we identified modifications in host cell proteins crucial for AAV mRNA stability and gene translation, particularly regarding AAV capsid transcripts under optimal transfection conditions. Our study identified 124 host proteins associated with AAV replication and assembly, each exhibiting distinct expression pattern throughout rAAV production stages in optimal transfection condition. This investigation sheds light on the cellular mechanisms involved in rAAV production in HEK293T cells and proposes promising avenues for further enhancing rAAV titer during production.

The impact of positive surgical margin parameters and pathological stage on biochemical recurrence after radical prostatectomy: A systematic review and meta-analysis.

BACKGROUND: To systematically review and perform a meta-analysis on the predictive value of the primary Gleason grade (PGG) at the positive surgical margin (PSM), length of PSM, number of PSMs, and pathological stage of the primary tumor on biochemical recurrence (BCR) in patients with prostate cancer (PCa) after radical prostatectomy (RP). METHODS: A systematic literature search was performed using electronic databases, including PubMed, EMBASE, Cochrane Library, and Web of Science, from January 1, 2005, to October 1, 2023. The protocol was pre-registered in PROSPERO. Subgroup analyses were performed according to the different treatments and study outcomes. Pooled hazard ratios with 95% confidence intervals were extracted from multivariate analyses, and a fixed or random effect model was used to pool the estimates. Subgroup analyses were performed to explore the reasons for the heterogeneity. RESULTS: Thirty-one studies that included 50,028 patients with PCa were eligible for this meta-analysis. The results showed that, compared to PGG3, PGG4/5 was associated with a significantly increased risk of BCR. Compared with PSM ≤3 mm, PSM ≥3 mm was associated with a significantly increased risk of BCR. Compared with unifocal PSM, multifocal PSM (mF-PSM) was associated with a significantly increased risk of BCR. In addition, pT >2 was associated with a significantly increased risk of BCR compared to pT2. Notably, the findings were found to be reliable based on the sensitivity and subgroup analyses. CONCLUSIONS: PGG at the PSM, length of PSM, number of PSMs, and pathological stage of the primary tumor in patients with PCa were found to be associated with a significantly increased risk of BCR. Thus, patients with these factors should be treated differently in terms of receiving adjunct treatment and more frequent monitoring. Large-scale, well-designed prospective studies with longer follow-up periods are needed to validate the efficacy of these risk factors and their effects on patient responses to adjuvant and salvage therapies and other oncological outcomes.

Heterologous Expression and Biochemical Characterization of a Novel Lytic Polysaccharide Monooxygenase from Chitinilyticum aquatile CSC-1.

Lytic polysaccharide monooxygenases (LPMOs) are copper-dependent enzymes that catalyze the oxidative cleavage of recalcitrant polysaccharides. There are limited reports on LPMOs capable of concurrently catalyzing the oxidative cleavage of both cellulose and chitin. In this study, we identified and cloned a novel LPMO from the newly isolated bacterium Chitinilyticum aquatile CSC-1, designated as CaLPMO10. When using 2, 6-dimethylphenol (2, 6-DMP) as the substrate, CaLPMO10 exhibited optimal activity at 50 °C and pH 8, demonstrating good temperature stability at 30 °C. Even after a 6 h incubation at pH 8 and 30 °C, CaLPMO10 retained approximately 83.03 ± 1.25% residual enzyme activity. Most metal ions were found to enhance the enzyme activity of CaLPMO10, with ascorbic acid identified as the optimal reducing agent. Mass spectrometry analysis indicated that CaLPMO10 displayed oxidative activity towards both chitin and cellulose, identifying it as a C1/C4-oxidized LPMO. CaLPMO10 shows promise as a key enzyme for the efficient utilization of biomass resources in future applications.

Gut microbiota regulates gut homeostasis, mucosal immunity and influences immune-related diseases.

The intestinal microbiome constitutes a sophisticated and massive ecosystem pivotal for maintaining gastrointestinal equilibrium and mucosal immunity via diverse pathways. The gut microbiota is continuously reshaped by multiple environmental factors, thereby influencing overall wellbeing or predisposing individuals to disease state. Many observations reveal an altered microbiome composition in individuals with autoimmune conditions, coupled with shifts in metabolic profiles, which has spurred ongoing development of therapeutic interventions targeting the microbiome. This review delineates the microbial consortia of the intestine, their role in sustaining gastrointestinal stability, the association between the microbiome and immune-mediated pathologies, and therapeutic modalities focused on microbiome modulation. We emphasize the entire role of the intestinal microbiome in human health and recommend microbiome modulation as a viable strategy for disease prophylaxis and management. However, the application of gut microbiota modification for the treatment of immune-related diseases, such as fecal microbiota transplantation and probiotics, remain quite challenging. Therefore, more research is needed into the role and mechanisms of these therapeutics.

Generation of attosecond gigawatt soft x-ray pulses through coherent Thomson backscattering.

Collision between relativistic electron sheets and counterpropagating laser pulses is recognized as a promising way to produce intense attosecond x rays through coherent Thomson backscattering (TBS). In a double-layer scheme, the electrons in an ultrathin solid foil are first pushed out by an intense laser driver and then interact with the laser reflected off a second foil to form a high-density relativistic electron sheet with vanishing transverse momentum. However, the repulsion between these concentrated electrons can increase the thickness of the layer, reducing both its density and subsequently the coherent TBS. Here, we present a systematic study on the evolution of the flying electron layer and find that its resulting thickness is determined by the interplay between the intrinsic space-charge expansion and the velocity compression induced by the drive laser. How the laser driver, the target areal density, the reflector, and the collision laser intensity affect the properties of the produced x rays is explored. Multidimensional particle-in-cell simulations indicate that employing this scheme in the nonlinear regime has the potential to stably produce soft x rays with several gigawatt peak power in hundreds of terawatt ultrafast laser facilities. The pulse duration can be tuned to tens of attoseconds. This compact and intense attosecond x-ray source may have broad applications in attosecond science.