Subject-Independent Wearable P300 Brain-Computer Interface Based on Convolutional Neural Network and Metric Learning.

The calibration procedure for a wearable P300 brain-computer interface (BCI) greatly impact the user experience of the system. Each user needs to spend additional time establishing a decoder adapted to their own brainwaves. Therefore, achieving subject independent is an urgent issue for wearable P300 BCI needs to be addressed. A dataset of electroencephalogram (EEG) signals was constructed from 100 individuals by conducting a P300 speller task with a wearable EEG amplifier. A framework is proposed that initially improves cross- subject consistency of EEG features through a common feature extractor. Subsequently, a simple and compact convolutional neural network (CNN) architecture is employed to learn an embedding sub-space, where the mapped EEG features are maximally separated, while pursuing the minimum distance within the same class and the maximum distance between different classes. Finally, the model's generalization capability was further optimized through fine-tuning. Results: The proposed method significantly boosts the average accuracy of wearable P300 BCI to 73.23±7.62 % without calibration and 78.75±6.37 % with fine-tuning. The results demonstrate the feasibility and excellent performance of our dataset and framework. A calibration-free wearable P300 BCI system is feasible, suggesting significant potential for practical applications of the wearable P300 BCI system.

Mrc1 regulates parental histone segregation and heterochromatin inheritance.

Chromatin-based epigenetic memory relies on the symmetric distribution of parental histones to newly synthesized daughter DNA strands, aided by histone chaperones within the DNA replication machinery. However, the mechanism of parental histone transfer remains elusive. Here, we reveal that in fission yeast, the replisome protein Mrc1 plays a crucial role in promoting the transfer of parental histone H3-H4 to the lagging strand, ensuring proper heterochromatin inheritance. In addition, Mrc1 facilitates the interaction between Mcm2 and DNA polymerase alpha, two histone-binding proteins critical for parental histone transfer. Furthermore, Mrc1's involvement in parental histone transfer and epigenetic inheritance is independent of its known functions in DNA replication checkpoint activation and replisome speed control. Instead, Mrc1 interacts with Mcm2 outside of its histone-binding region, creating a physical barrier to separate parental histone transfer pathways. These findings unveil Mrc1 as a key player within the replisome, coordinating parental histone segregation to regulate epigenetic inheritance.

Exposure to anti-seizure medication during pregnancy and the risk of autism and ADHD in offspring: a systematic review and meta-analysis.

Background: Evidence of an association between maternal use of anti-seizure medication (ASM) during pregnancy and the risk of autism spectrum disorder (ASD) or attention-deficit/hyperactivity disorder (ADHD) in children is conflicting. This systematic review and meta-analysis aimed to summarize the relationship between fetal exposure to ASM and the development of ASD or ADHD in offspring. Methods: A comprehensive literature search was conducted in PubMed and other databases to identify relevant epidemiological studies published from inception until 1 March 2024. Results: Seven cohort studies were included in the meta-analysis. The results showed that maternal exposure to ASMs during pregnancy was associated with an increased risk of ASD [odds ratio (OR): 2.1, 95% confidence interval (CI): 1.63-2.71; p < 0.001] in the general population. This association became weaker (ASD: OR: 1.38, 95% CI: 1.11-1.73; p = 0.004) when the reference group was mothers with a psychiatric disorder or epilepsy not treated during pregnancy. Furthermore, an increased risk of ADHD was observed when the study data adjusted for drug indications were pooled (OR: 1.43, 95% CI: 1.07-1.92; p = 0.015). In subgroup analyses based on individual ASM use, only exposure to valproate preconception was significantly associated with an increased risk of ASD or ADHD. Conclusion: The significant association between maternal ASM use during pregnancy and ASD or ADHD in offspring may be partially explained by the drug indication or driven by valproate.

Exploring noninvasive matrices for assessing long-term exposure to phthalates: a scoping review.

The phthalic acid esters (PAEs) are one class of the most abundant and frequently studied pseudo-persistent organic pollutants. Noninvasive urine is an effective substrate for evaluating PAE exposure, but repeated sampling is needed to overcome this bias. This adds much work to on-site collection and the cost of detection increases exponentially. Therefore, the aim of this study was to conduct a scope review to describe the detection methods and validity of the use of other noninvasive matrices, such as nails and hair, for assessing long-term exposure to PAEs. The PubMed, Web of Science and China National Knowledge Infrastructure (CNKI), electronic databases were searched from 1 January 2000 to 3 April 2024, and 12 studies were included. Nine and three studies used hair and nails, respectively, as noninvasive matrices for detecting PAE exposure. Five articles compared the results of nail or hair and urine tests for validity of the assessment of PAE exposure. The preprocessing and detection methods for these noninvasive samples are also described. The results of this review suggest that, compared with nails, hair may be more suitable as a noninvasive alternative matrix for assessing long-term exposure to PAEs. However, sample handling procedures such as the extraction and purification of compounds from hair are not uniform in various studies; therefore, further exploration and optimization of this process, and additional research evidence to evaluate its effectiveness, are needed to provide a scientific basis for the promotion and application of hair detection methods for assessing long-term PAE exposure levels.

Health hazards of preconception phthalate exposure: A scoping review of epidemiology studies.

There is a close relationship between preconception health and maternal and child health outcomes, and the consequences may be passed down from generation to generation. In 2018, Lancet published three consecutive articles emphasizing the importance of the preconception period. Phthalic acid ester (PAE) exposure during this period may affect gametogenesis and epigenetic information in gametophytes, thereby affecting embryonic development and offspring health. Therefore, this article reviews the effects of parental preconception PAE exposure on reproductive/birth outcomes and offspring health, to provide new evidence on this topic. We searched Web of Science, MEDLINE (through PubMed), the China National Knowledge Infrastructure (CNKI), ScienceDirect, and the VIP Journal Library from the date of database establishment to July 3, 2024. Finally, 12 articles were included. Three studies investigated the health hazards (effects on birth weight, abortion, etc.) of women's preconception PAE exposure. Nine studies involved both parents. Nine studies considered the impacts of PAE preconception exposure on reproductive/birth outcomes, focusing on birth weight, pregnancy loss, preterm birth, embryo quality, and placental weight. Three studies considered the impacts of preconception PAE exposure on offspring behavior. The results of this review suggested that parental preconception PAE exposure may have an impact on reproductive/birth outcomes and offspring behavior, including birth weight, child behavior, and dietary behavior. However, studies on the health hazards of preconception PAE exposure are relatively scarce, and the outcomes of current studies are varied. It is necessary to use systematic reviews to verify an accurate research question to provide recommendations for public health policy making.

Active volatile components of the preferred hosts are potential attractants to Hyphantria cunea adults.

The extraordinary adaptability and dispersal abilities have allowed Hyphantria cunea to expand its range, posing a great threat to urban landscapes and natural ecosystems. Searching for safe, efficient, and low-cost control methods may provide new strategies for pest management in H. cunea spread areas. In this study, based on the attraction of insects by preferred hosts, it was found that the response rates of virgin H. cunea female adults to Salix matsudana, Juglans mandshurica and Ulmus pumila were 89.17%, 97.92% and 93.98%, respectively. It was further found that this significant preference was mainly related to the volatiles m-xylene, o-xylene, dodecane and tetradecane found in the three species. Even though all four compounds at 10 µL/mL and 100 µL/mL had significant attractive effects on the virgin H. cunea female adults, m-xylene and dodecane at 100 µL/mL elicited significant EAG responses and tending behaviors by stimulating the olfactory receptor neurons (ORN A) of females, with response rates of 83.13% and 84.17%, while also having significant attractive effects on virgin male adults with rates of 65.74% and 67.51%. Therefore, both m-xylene and dodecane which at concentrations of 100 µL/mL had strong attractions to adults, could be used as the first choice of attractants for both sexes of H. cunea. This has important practical significance in reducing the frequency of H. cunea generations, limiting their population, controlling their spread range, and improving the efficiency of pest management in epidemic areas.

Incidence and prognosis of olfactory and gustatory dysfunctions related to SARS-CoV-2 Omicron strain infection in China: A national multicenter survey of 35,566 individuals.

Objective: This cross-sectional study aimed to determine the epidemiology of olfactory and gustatory dysfunctions related to COVID-19 in China. Methods: This study was conducted by 45 tertiary Grade-A hospitals in China. Online and offline questionnaire data were obtained from patients infected with COVID-19 between December 28, 2022, and February 21, 2023. The collected information included basic demographics, medical history, smoking and drinking history, vaccination history, changes in olfactory and gustatory functions before and after infection, and other postinfection symptoms, as well as the duration and improvement status of olfactory and gustatory disorders. Results: Complete questionnaires were obtained from 35,566 subjects. The overall incidence of olfactory and taste dysfunction was 67.75%. Being female or being a cigarette smoker increased the likelihood of developing olfactory and taste dysfunction. Having received four doses of the vaccine or having good oral health or being a alcohol drinker decreased the risk of such dysfunction. Before infection, the average olfactory and taste VAS scores were 8.41 and 8.51, respectively; after infection, they decreased to 3.69 and 4.29 and recovered to 5.83 and 6.55 by the time of the survey. The median duration of dysosmia and dysgeusia was 15 and 12 days, respectively, with 0.5% of patients having symptoms lasting for more than 28 days. The overall self-reported improvement rate was 59.16%. Recovery was higher in males, never smokers, those who received two or three vaccine doses, and those that had never experienced dental health issues, or chronic accompanying symptoms. Conclusions: The incidence of dysosmia and dysgeusia following infection with the SARS-CoV-2 virus is high in China. Incidence and prognosis are influenced by several factors, including sex, SARS-CoV-2 vaccination, history of head-facial trauma, nasal and oral health status, smoking and drinking history, and the persistence of accompanying symptoms.

Blockage of L2HGDH-mediated S-2HG catabolism orchestrates macrophage polarization to elicit antitumor immunity.

The high infiltration of tumor-associated macrophages (TAMs) in the immunosuppressive tumor microenvironment prominently attenuates the efficacy of immune checkpoint blockade (ICB) therapies, yet the underlying mechanisms are not fully understood. Here, we investigate the metabolic profile of TAMs and identify S-2-hydroxyglutarate (S-2HG) as a potential immunometabolite that shapes macrophages into an antitumoral phenotype. Blockage of L-2-hydroxyglutarate dehydrogenase (L2HGDH)-mediated S-2HG catabolism in macrophages promotes tumor regression. Mechanistically, based on its structural similarity to α-ketoglutarate (α-KG), S-2HG has the potential to block the enzymatic activity of 2-oxoglutarate-dependent dioxygenases (2-OGDDs), consequently reshaping chromatin accessibility. Moreover, S-2HG-treated macrophages enhance CD8+ T cell-mediated antitumor activity and sensitivity to anti-PD-1 therapy. Overall, our study uncovers the role of blockage of L2HGDH-mediated S-2HG catabolism in orchestrating macrophage antitumoral polarization and, further, provides the potential of repolarizing macrophages by S-2HG to overcome resistance to anti-PD-1 therapy.

Perceived stress and influencing factors for the people at high risk to COVID-19 in centralized quarantine camps in Wenzhou, China.

BACKGROUND: This study was designed to assess stress levels and related factors during the coronavirus disease 2019 (COVID-19) epidemic among individuals in centralized quarantine camps in Wenzhou, China. METHODS: The survey was conducted using a questionnaire. The questionnaire included questions on sociodemographic characteristics, life events related to the COVID-19 and stressful situations, as well as Perceived Stress Scale-14. Participants included close contacts of patients with COVID-19 or at-risk individuals in quarantine camps. Multivariate logistic regression was used to analyze different factors affecting perceived stress. RESULTS: The prevalence of high stress among quarantine camp participants was 37.45%. Of the 881 respondents, 51.99% were concerned about the difficulty of controlling the epidemic, 46.20% were concerned about the health of themselves and their family members and 39.61% were concerned about not being able to leave their homes. Multivariate logistic regression analysis revealed statistically significant differences in the prevalence of stress among different groups for certain variables, including occupation, education level and knowledge of COVID-19 (all P < 0.05). Our study found that at-risk individuals and close contacts experienced high levels of stress in quarantine camps during the COVID-19 pandemic. CONCLUSIONS: These findings suggest that centralized quarantine policies should be adapted and optimized to minimize negative psychological effects on quarantined individuals.

Electroacupuncture modulates abnormal brain connectivity after ischemia reperfusion injury in rats: A graph theory-based approach.

BACKGROUND: Electroacupuncture (EA) has been shown to facilitate brain plasticity-related functional recovery following ischemic stroke. The functional magnetic resonance imaging technique can be used to determine the range and mode of brain activation. After stroke, EA has been shown to alter brain connectivity, whereas EA's effect on brain network topology properties remains unclear. An evaluation of EA's effects on global and nodal topological properties in rats with ischemia reperfusion was conducted in this study. METHODS AND RESULTS: There were three groups of adult male Sprague-Dawley rats: sham-operated group (sham group), middle cerebral artery occlusion/reperfusion (MCAO/R) group, and MCAO/R plus EA (MCAO/R + EA) group. The differences in global and nodal topological properties, including shortest path length, global efficiency, local efficiency, small-worldness index, betweenness centrality (BC), and degree centrality (DC) were estimated. Graphical network analyses revealed that, as compared with the sham group, the MCAO/R group demonstrated a decrease in BC value in the right ventral hippocampus and increased BC in the right substantia nigra, accompanied by increased DC in the left nucleus accumbens shell (AcbSh). The BC was increased in the right hippocampus ventral and decreased in the right substantia nigra after EA intervention, and MCAO/R + EA resulted in a decreased DC in left AcbSh compared to MCAO/R. CONCLUSION: The results of this study provide a potential basis for EA to promote cognitive and motor function recovery after ischemic stroke.

The protective mechanism of Tao Hong Si Wu decoction against breast cancer through regulation of EGFR/ERK1/2 signaling.

ETHNOPHARMACOLOGICAL RELEVANCE: Tao Hong Si Wu Decoction (THSWD), a traditional Chinese herbal medicine, is widely utilized in clinical settings, either alone or in combination with other medications, for the treatment of breast cancer. AIM OF THE STUDY: The specific targeting molecule(s) of THSWD and its associated molecular mechanisms remain unclear. This research aims to elucidate the underlying molecular mechanisms of THSWD in the treatment of breast cancer. MATERIALS AND METHODS: The pharmacological properties of THSWD were investigated in breast cancer cells and tumor tissues using a range of methods including Acridine Orange/Ethidium Bromide (AO/EB) staining, Transwell assay, flow cytometry, immunofluorescence assay, and breast cancer mice models. RESULTS: Our findings demonstrate that THSWD induces necrosis and/or apoptosis in breast cancer cells, while significantly inhibiting cell migration. Target proteins of THSWD in anticancer activity include EGFR, RAS, and others. THSWD treatment for breast cancer is associated with the EGFR/ERK1/2 signaling pathway. CONCLUSION: Our findings offer initial insights into the primary mechanism of action of THSWD in breast cancer treatment, indicating its potential as a complementary therapy deserving further investigation.

Overview of the recent advances in porcine epidemic diarrhea vaccines.

Vaccination is the most effective means of preventing and controlling porcine epidemic diarrhea (PED). Conventional vaccines developed from porcine epidemic diarrhea virus (PEDV) GI-a subtypes (CV777 and SM98) have played a vital role in preventing classical PED. However, with the emergence of PEDV mutants in 2010, conventional PEDV GI-a subtype-targeting vaccines no longer provide adequate protection against PEDV GII mutants, thereby making novel-type PED vaccine development an urgent concern to be addressed. Novel vaccines, including nucleic acid vaccines, genetically engineered subunit vaccines, and live vector vaccines, are associated with several advantages, such as high safety and stability, clear targeting, high yield, low cost, and convenient usage. These vaccines can be combined with corresponding ELISA kits to differentiate infected from vaccinated animals, which is beneficial for disease confirmation. This review provides a detailed overview of the recent advancements in PED vaccines, emphasizing on the research and application evaluation of novel PED vaccines. It also considers the future directions and challenges in advancing these vaccines to widespread use in clinics.

Coordination of histone chaperones for parental histone segregation and epigenetic inheritance.

Chromatin-based epigenetic memory relies on the accurate distribution of parental histone H3-H4 tetramers to newly replicated DNA strands. Mcm2, a subunit of the replicative helicase, and Dpb3/4, subunits of DNA polymerase ε, govern parental histone H3-H4 deposition to the lagging and leading strands, respectively. However, their contribution to epigenetic inheritance remains controversial. Here, using fission yeast heterochromatin inheritance systems that eliminate interference from initiation pathways, we show that a Mcm2 histone binding mutation severely disrupts heterochromatin inheritance, while mutations in Dpb3/4 cause only moderate defects. Surprisingly, simultaneous mutations of Mcm2 and Dpb3/4 stabilize heterochromatin inheritance. eSPAN (enrichment and sequencing of protein-associated nascent DNA) analyses confirmed the conservation of Mcm2 and Dpb3/4 functions in parental histone H3-H4 segregation, with their combined absence showing a more symmetric distribution of parental histone H3-H4 than either single mutation alone. Furthermore, the FACT histone chaperone regulates parental histone transfer to both strands and collaborates with Mcm2 and Dpb3/4 to maintain parental histone H3-H4 density and faithful heterochromatin inheritance. These results underscore the importance of both symmetric distribution of parental histones and their density at daughter strands for epigenetic inheritance and unveil distinctive properties of parental histone chaperones during DNA replication.

Clinical characteristics and risk factors for Klebsiella pneumoniae bloodstream infection in 152 immunocompetent patients.

OBJECTIVE: To investigate the clinical characteristics and prognostic risk factors for Klebsiella pneumoniae bloodstream infections in immunocompetent patients. METHODS: The study included patients with K. pneumoniae bloodstream infection treated in Zhongda Hospital from June 2016 to June 2021. Clinical data and antibiotic susceptibility test results were retrospectively collected and analyzed. Independent risk factors for mortality were screened using the chi-square test and multivariate logistic regression. RESULTS: A total of 152 patients were included in the analysis. In our cohort, 77.6% of patients were older than 60 years, and 80.9% of them had community-acquired infections. The most common complications were type 2 diabetes, hypertension, and stroke sequelae. The proportion of patients with septic shock or abscesses was 34.9% and 25.7%, respectively. There were significant differences in the site of infection, septic shock, and serum levels of procalcitonin, hypersensitive C-reactive protein, D-dimer, creatinine, and lactic acid between survivors and non-survivors (p < 0.05). Multivariate regression analysis showed that hospital-acquired infections, septic shock, length of hospital stay, and creatinine levels were independent risk factors for mortality. Antibiotic susceptibility test results indicated that clinical outcomes varied depending on bacterial sensitivity to ampicillin/sulbactam. DISCUSSION: Klebsiella pneumoniae is a common community-acquired and hospital-acquired bacteria and usually infects older people with complications such as diabetes. Nosocomial infections, length of stay, septic shock, and renal insufficiency are potentially associated with poor prognosis. Bacterial susceptibility to ampicillin/sulbactam affects prognosis.

Comparison of Three Detection Methods for Seoul Virus Causing Hemorrhagic Fever with Renal Syndrome.

BACKGROUND: Seoul virus (SEOV) is a significant causative pathogen of hemorrhagic fever with renal syndrome (HFRS). Accurate discrimination of SEOV infection from other viral or bacterial infections holds vital clinical importance. METHODS: Our study utilized quantitative real-time PCR (qRT-PCR), metagenomic next-generation sequencing (mNGS), and immunological assays to identify the pathogen causing HFRS. RESULTS: For the case, mNGS identified SEOV and suspected host or environmental microorganisms at 5 days from symptom onset. qRT-PCR detected SEOV between 5 to 8 days from symptom onset. Anti-hantavirus IgM antibodies reached positive criteria at 7 days and IgG antibodies at 9 days from symptom onset. CONCLUSIONS: qRT-PCR, mNGS, and immunological assays each have merits and drawbacks. Optimal selection depends on laboratory conditions and clinical requirements.

An Efficient Homologous Recombination-Based In Situ Protein-Labeling Method in Verticillium dahliae.

Accurate determination of protein localization, levels, or protein-protein interactions is pivotal for the study of their function, and in situ protein labeling via homologous recombination has emerged as a critical tool in many organisms. While this approach has been refined in various model fungi, the study of protein function in most plant pathogens has predominantly relied on ex situ or overexpression manipulations. To dissect the molecular mechanisms of development and infection for Verticillium dahliae, a formidable plant pathogen responsible for vascular wilt diseases, we have established a robust, homologous recombination-based in situ protein labeling strategy in this organism. Utilizing Agrobacterium tumefaciens-mediated transformation (ATMT), this methodology facilitates the precise tagging of specific proteins at their C-termini with epitopes, such as GFP and Flag, within the native context of V. dahliae. We demonstrate the efficacy of our approach through the in situ labeling of VdCf2 and VdDMM2, followed by subsequent confirmation via subcellular localization and protein-level analyses. Our findings confirm the applicability of homologous recombination for in situ protein labeling in V. dahliae and suggest its potential utility across a broad spectrum of filamentous fungi. This labeling method stands to significantly advance the field of functional genomics in plant pathogenic fungi, offering a versatile and powerful tool for the elucidation of protein function.

Aberrant DNA repair reveals a vulnerability in histone H3.3-mutant brain tumors.

Pediatric high-grade gliomas (pHGG) are devastating and incurable brain tumors with recurrent mutations in histone H3.3. These mutations promote oncogenesis by dysregulating gene expression through alterations of histone modifications. We identify aberrant DNA repair as an independent mechanism, which fosters genome instability in H3.3 mutant pHGG, and opens new therapeutic options. The two most frequent H3.3 mutations in pHGG, K27M and G34R, drive aberrant repair of replication-associated damage by non-homologous end joining (NHEJ). Aberrant NHEJ is mediated by the DNA repair enzyme polynucleotide kinase 3'-phosphatase (PNKP), which shows increased association with mutant H3.3 at damaged replication forks. PNKP sustains the proliferation of cells bearing H3.3 mutations, thus conferring a molecular vulnerability, specific to mutant cells, with potential for therapeutic targeting.

Effectiveness and brain mechanism of multi-target transcranial alternating current stimulation (tACS) on motor learning in stroke patients: study protocol for a randomized controlled trial.

BACKGROUND: Transcranial alternating current stimulation (tACS) has proven to be an effective treatment for improving cognition, a crucial factor in motor learning. However, current studies are predominantly focused on the motor cortex, and the potential brain mechanisms responsible for the therapeutic effects are still unclear. Given the interconnected nature of motor learning within the brain network, we have proposed a novel approach known as multi-target tACS. This study aims to ascertain whether multi-target tACS is more effective than single-target stimulation in stroke patients and to further explore the potential underlying brain mechanisms by using techniques such as transcranial magnetic stimulation (TMS) and magnetic resonance imaging (MRI). METHODS: This study employs a double-blind, sham-controlled, randomized controlled trial design with a 2-week intervention period. Both participants and outcome assessors will remain unaware of treatment allocation throughout the study. Thirty-nine stroke patients will be recruited and randomized into three distinct groups, including the sham tACS group (SS group), the single-target tACS group (ST group), and the multi-target tACS group (MT group), at a 1:1:1 ratio. The primary outcomes are series reaction time tests (SRTTs) combined with electroencephalograms (EEGs). The secondary outcomes include motor evoked potential (MEP), central motor conduction time (CMCT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), magnetic resonance imaging (MRI), Box and Block Test (BBT), and blood sample RNA sequencing. The tACS interventions for all three groups will be administered over a 2-week period, with outcome assessments conducted at baseline (T0) and 1 day (T1), 7 days (T2), and 14 days (T3) of the intervention phase. DISCUSSION: The study's findings will determine the potential of 40-Hz tACS to improve motor learning in stroke patients. Additionally, it will compare the effectiveness of multi-target and single-target approaches, shedding light on their respective improvement effects. Through the utilization of techniques such as TMS and MRI, the study aims to uncover the underlying brain mechanisms responsible for the therapeutic impact. Furthermore, the intervention has the potential to facilitate motor learning efficiency, thereby contributing to the advancement of future stroke rehabilitation treatment. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300073465. Registered on 11 July 2023.

GetPrimers: A generalized PCR-based genetic targeting primer designer enabling easy and standardized targeted gene modification across multiple systems.

Genetic targeting (e.g., gene knockout and tagging) based on polymerase chain reaction (PCR) is a simple yet powerful approach for studying gene functions. Although originally developed in classic budding and fission yeast models, the same principle applies to other eukaryotic systems with efficient homologous recombination. One-step PCR-based genetic targeting is conventionally used but the sizes of the homologous arms that it generates for recombination-mediated genetic targeting are usually limited. Alternatively, gene targeting can also be performed via fusion PCR, which can create homologous arms that are orders of magnitude larger, therefore substantially increasing the efficiency of recombination-mediated genetic targeting. Here, we present GetPrimers (https://www.evomicslab.org/app/getprimers/), a generalized computational framework and web tool to assist automatic targeting and verification primer design for both one-step PCR-based and fusion PCR-based genetic targeting experiments. Moreover, GetPrimers by design runs for any given genetic background of any species with full genome scalability. Therefore, GetPrimers is capable of empowering high-throughput functional genomic assays at multipopulation and multispecies levels. Comprehensive experimental validations have been performed for targeting and verification primers designed by GetPrimers across multiple organism systems and experimental setups. We anticipate GetPrimers to become a highly useful and popular tool to facilitate easy and standardized gene modification across multiple systems.

[Analysis of VOCs Emission Characteristics and Emission Reduction Potential of Typical Industries in Jinan, China].

Based on the air pollutant emission inventory of Jinan in 2020, the VOCs emission status and existing problems of typical industries including the chemical industry, industrial coating, printing, and furniture manufacturing were investigated and analyzed, and two emission reduction scenarios were designed to estimate the emission reduction potential according to the enterprise scales and the end-of-pipe treatment techniques. The results showed that the VOCs emissions of the typical industries from large to small were the chemical industry(7947.92 t), industrial coating(2383.29 t), printing(792.87 t), and furniture manufacturing(143.79 t). The chemical industry and industrial painting were dominated by large enterprises, accounting for 46.45% and 50.89% of VOCs emissions, whereas printing and furniture manufacturing were dominated by medium-sized enterprises, accounting for 51.76% and 42.37% of VOCs emissions, respectively. The end-of-pipe treatment was dominated by a single inefficient treatment technique, and the utilization rate of efficient treatment techniques such as combustion techniques and combination techniques was only 7.46%. The on-site investigation reported some problems in some enterprises, including incomplete source substitution, inadequate management of fugitive emissions, and unsuitable end-of-pipe treatment facilities. Therefore, VOCs emissions of typical industries had a certain reduction potential. Under the two designed emission reduction scenarios, the chemical industry had the greatest emission reduction potential, with emission reduction rates of 69.58%-84.99%, and the emission reduction rates of industrial coating, printing, and furniture manufacturing industries were 26.98%-34.74%, 36.96%-59.74%, and 8.55%-40.45%, respectively. Among the four industries, large and medium-sized enterprises had greater emission reduction potential, with average emission reduction rates of 70.00% and 44.23%, respectively. Under the scenario of a higher emission reduction target, the average emission reduction rates of small and micro enterprises were greatly increased, reaching 87.49% and 79.65%, respectively. The results of this study could provide scientific basis for developing VOCs governance in typical industries and enterprises.