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Heterogeneous activation of peracetic acid (PAA) process is a promising method for removing organic pollutants from water. Nevertheless, this process is constrained by several complex factors, such as the selection of catalysts, optimization of reaction conditions, and identification of mechanism. In this study, a task decomposition strategy was adopted by combining a catalyst and reaction condition optimization machine learning (CRCO-ML) model and a mechanism identification machine learning (MI-ML) model to address these issues. The Categorical Boosting (CatBoost) model was identified as the best-performing model for the dataset (1024 sets and 7122 data points) in this study, achieving an R2 of 0.92 and an RMSE of 1.28. Catalyst composition, PAA dosage, and catalyst dosage were identified as the three most important features through SHAP analysis in the CRCO-ML model. The HCO3- is considered the most influential water matrix affecting the k value. The errors between all reverse experiment results and the predictions of the CRCO-ML and MI-ML models were <10 % and 15 %, respectively. This interdisciplinary work provides novel insights into the design and application of the heterogeneous activation of PAA process, significantly contributing to the rapid development of this technology.

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Reference electrode (RE) plays the core role in accurate potential control in electrochemistry. However, nanoresolved electrochemical characterization techniques still suffer from unstable potential control of pseudo-REs, because the commercial RE is too large to be used in the tiny electrochemical cell, and thus only pseudo-RE can be used. Therefore, microsized RE with a stable potential is urgently required to push the nanoresolved electrochemical measurements to a new level of accuracy and precision, but it is quite challenging to reproducibly fabricate such a micro RE until now. Here, we revisited the working mechanism of the metal-junction RE and clearly revealed the role of the ionic path between the metal wire and the borosilicate glass capillary to maintain a stable potential of RE. Based on this understanding, we developed a method to fabricate micro ultrastable-RE, where a reproducible ultrathin ionic path can form by dissolving a sandwiched sacrificial layer between the Pt wire and the capillary for the ion transfer. The potential of this new micro RE was almost the same as that of the commercial Ag/AgCl electrode, while the size is much smaller. Different from commercial REs that must be stored in the inner electrolyte, the new RE could be directly stored in air for more than one year without potential drift. Eventually, we successfully applied the micro RE in the electrochemical tip-enhanced Raman spectroscopy (EC-TERS) measurement to precisely control the potential of the working electrode, which makes it possible to compare the results from different laboratories and techniques to better understand the electrochemical interface at the nanoscale.

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Materials and their interfaces are the core for the development of a large variety of fields, including catalysis, energy storage and conversion. In this case, tip-enhanced Raman spectroscopy (TERS), which combines scanning probe microscopy with plasmon-enhanced Raman spectroscopy, is a powerful technique that can simultaneously obtain the morphological information and chemical fingerprint of target samples at nanometer spatial resolution. It is an ideal tool for the nanoscale chemical characterization of materials and interfaces, correlating their structures with chemical performances. In this review, we begin with a brief introduction to the nanoscale characterization of materials and interfaces, followed by a detailed discussion on the recent theoretical understanding and technical improvements of TERS, including the origin of enhancement, TERS instruments, TERS tips and the application of algorithms in TERS. Subsequently, we list the key experimental issues that need to be addressed to conduct successful TERS measurements. Next, we focus on the recent progress of TERS in the study of various materials, especially the novel low-dimensional materials, and the progresses of TERS in studying different interfaces, including both solid-gas and solid-liquid interfaces. Finally, we provide an outlook on the future developments of TERS in the study of materials and interfaces.

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BACKGROUND: Gastroesophageal reflux disease (GERD) refers to a clinical condition characterized by gastric content reflux into the esophagus, causing symptoms like acid regurgitation and heartburn. While patient education is essential for GERD treatment, traditional educational models often struggle to effectively improve treatment outcomes. METHODS: Between January 2021 and April 2022, we enrolled 257 patients and assessed their GERD knowledge. The patients were randomly assigned to either the WeChat group (60 participants) for health education via WeChat platform or the control group (60 participants) for conventional education only. GERD-Q scores were collected at 1, 3, and 6 months post-intervention, with compliance and satisfaction assessed at the study's conclusion. RESULTS: The overall awareness rate of GERD among patients was approximately 22.3 %. The WeChat group showed better compliance than the control group in terms of adhering to a proper diet, taking medication on time, and engaging in moderate exercise (P < 0.05 for all). Furthermore, the WeChat group demonstrated significantly higher treatment effectiveness and satisfaction than the control group (P < 0.05 for all). CONCLUSION: Patients have a relatively low level of knowledge regarding GERD. WeChat has the potential to facilitate lifestyle changes and improve compliance, treatment effectiveness, and treatment satisfaction among patients with gastroesophageal reflux disease.

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INTRODUCTION: Aflatoxins, potent carcinogens produced by Aspergillus species, present significant health risks and commonly contaminate herbal products such as Chrysanthemum morifolium. Detecting these toxins in C. morifolium proves challenging due to the complex nature of the herbal matrix and the fluctuating levels of toxins found in different samples. OBJECTIVES: This study aimed to develop and optimize a novel method for the detection of aflatoxins in C. morifolium using dispersive liquid-liquid microextraction combined with high-performance liquid chromatography-fluorescence detection based on quality by design principles. METHODOLOGY: The method involved determining critical method attributes and parameters through the Plackett-Burman design, followed by optimization using the Box-Behnken design. Monte Carlo simulation was employed to establish a design space, which was experimentally verified. Method validation was performed to confirm accuracy, precision, and stability. RESULTS: The developed method exhibited excellent linearity (R2 > 0.9991) for aflatoxins B1, B2, G1, and G2 across a range of concentrations, with recovery rates between 85.52% and 102.01%. The validated method effectively quantified aflatoxins in C. morifolium under different storage conditions, highlighting the impact of temperature and storage time on aflatoxin production. CONCLUSION: This study successfully established a reliable and effective method for the detection of aflatoxins in C. morifolium, highlighting the importance of strict storage conditions to reduce aflatoxin contamination. Using a quality by design framework, the method demonstrated robustness and high analytical performance, making it suitable for routine quality control of herbal products.

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Background: Microvascular invasion (MVI) is associated with an unfavorable prognosis and early recurrence of hepatocellular carcinoma (HCC), which is the crucial pathological hallmark of immunotherapy. While microvascular invasion (MVI) in hepatocellular carcinoma (HCC) currently lacks a detailed single-cell analysis of the tumor microenvironment (TME), it holds significant promise for immunotherapy using immune checkpoint inhibitors (ICI). Methods: We performed single-cell RNA sequencing (scRNA-seq) on 3 MVI positive (MVIP) and 14 MVI-negative (MVIN) tumor tissues, as well as their paired adjacent non-tumoral tissues. Results: We identified SPP1+ macrophages and CD4+ proliferative T cells as intertumoral populations critical for the formation of cold tumors and immunosuppressive environments in MVI-positive patients and verified their prognostic value in correlation with MVIP HCC patients. Additionally, we identified SPP1+ dominated interactions between SPP1+ macrophages and the immunosuppressive T population as contributors to MVI destruction and tumorigenesis. Conclusions: We provide a comprehensive single-cell atlas of HCC patients with MVI, shedding light on the immunosuppressive ecosystem and upregulated signaling associated with MVI. These findings demonstrate that intercellular mechanisms drive MVI and provide a potential immunotherapeutic target for HCC patients with HCC and underlying MVI.

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The group standard Guidelines for construction of traditional Chinese medicine(TCM) pharmacovigilance system in medical institutions, managed by Chinese Association of Chinese Medicine and led by the Institute of Basic Research in Clinical Medicine,China Academy of Chinese Medical Sciences and Dongfang Hospital of Beijing University of Chinese Medicine, was announced on National Group Standard Information Platform on January 16, 2024, with the standard number T/CACM 1563. 2-2024. According to EU pharmacovigilance regulations and the second-level guidance principles of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), the unique characteristics of TCM were fully considered, and the relevant systems and procedures for constructing TCM pharmacovigilance systems in medical institutions were clearly defined. This included establishing TCM pharmacovigilance information platforms, arranging staff, formulating various regulations, and monitoring adverse reactions of TCM(including TCM decoction pieces, granules, Chinese patent medicines, in-hospital preparations, and pre-marketed Chinese patent medicines). It aimed to develop a TCM pharmacovigilance system in medical institutions that was tailored to the characteristics of TCM. The system could be appropriately adjusted according to the scope of practice and actual circumstances of medical institutions at different levels. This will enhance the implementation of TCM pharmacovigilance work and safeguard medication safety. The group standard underwent multiple rounds of consultations with internal and external experts and has ultimately evolved into a guiding document applicable to medical institutions and related entities engaged in pharmacovigilance activities.

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Oral Chinese patent medicine is the essence of effective prescriptions created and summarized by Chinese medical scientists through thousands of years of medical practice. It is portable and convenient, with an obvious curative effect and other characteristics. However, at present, oral Chinese patent medicine is rich in dosage forms, various in types, complex in mechanism of action, and broad in clinical positioning. In clinical application, there are often cases of drug use without reference to instructions,repeated drug use, and prolonged drug use, which highlights safety problems such as adverse reactions and hepatorenal toxicity. Oral Chinese patent medicine pharmacovigilance is facing challenges. World Health Organization(WHO) has issued the WHO guidelines on safety monitoring of herbal medicines in pharmacovigilance systems, and International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use(ICH) has issued the ICH E2 pharmacovigilance guidelines. The United States has issued the Pharmacovigilance management standards and pharmacoepidemiological assessment guidelines, and the European Union has issued the Guidelines on good pharmacovigilance practices. Japan, South Korea, and other countries in the Asia Pacific region have established their own pharmacovigilance systems, but currently, there are no pharmacovigilance guidelines related to oral Chinese patent medicine in China. Therefore, experts from many disciplines and fields in China were invited to jointly develop the Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines, which aims to develop pharmacovigilance guidelines for clinical application that are consistent with China's national conditions and highlight the characteristics of oral Chinese patent medicine, and provide guidance for clinically safe and rational drug application in medical institutions.

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There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

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Drug administration law of the People's Republic of China(2019 revised edition), which came into effect on December 1, 2019, proposed that " the state shall establish a pharmacovigilance system". Pharmacovigilance work of Chinese patent medicines is more difficult, and it is necessary to carry out Pharmacovigilance activities that are in line with the characteristics of Chinese patent medicines. Pharmacovigilance guidelines of Chinese patent medicines(T/CACM 1563. 1-2024), based on the principles of Drug Administration Law of the People's Republic of China(2019 revised edition) and Pharmacovigilance quality management standards(No. 65 of 2021) of the National Medical Products Administration, draws on the EU Pharmacovigilance regulation and the secondary guidelines of International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH), and it is drafted in accordance with the provisions of Guidelines for standardization work part 1: structure and drafting rules of standardization documents(GB/T1. 1-2020) based on the characteristics of Chinese patent medicines. It serves as a general document for a series of pharmacovigilance guidelines of Chinese patent medicines, such as Guidelines for construction of traditional Chinese medicine pharmacovigilance system in medical institutions(T/CACM 1563. 2-2024), Pharmacovigilance guidelines for clinical application of oral Chinese patent medicines(T/CACM 1563. 3-2024), Pharmacovigilance guidelines for clinical application of traditional Chinese medicine injections(T/CACM 1563. 4-2024), Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use(T/CACM 1563. 5-2024), and Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration(T/CACM 1563. 6-2024), including four major elements of pharmacovigilance monitoring and reporting of Chinese patent medicines, signal identification, risk evaluation, and risk control, as well as pharmacovigilance activities for Chinese patent medicines, ensuring the safety of public drug use.

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The group standard Pharmacovigilance guidelines for clinical application of Chinese patent medicines for mucosal administration was released on January 16, 2024, on the national group standards information platform by the Institute of Basic Research in Clinical Medicine of China Academy of Chinese Medical Sciences and School and Hospital of Stomatology of Peking University, under the centralized management by the China Association of Chinese Medicine. The standard number is T/CACM 1563.6-2024. It aims to propose key elements and specify technical methods for safety monitoring and reporting, signal identification, risk assessment, and risk control based on the Drug administration law of the People's Republic of China(revised in 2019), which establishes normative pharmacovigilance guideline of Chinese patent medicine for mucosal administration that is in line with the characteristics of traditional Chinese Medicine(TCM) based on the pharmacovigilance content for clinical application of Chinese patent medicine for mucosal administration. The group standard has been discussed by internal and external experts through multiple rounds of consultation. It serves as a guiding document for stakeholders involved in pharmacovigilance activities, including pharmaceutical license holders, drug manufacturers, medical institutions, research institutes, and pharmaceutical trading enterprises.

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Glutathione (GSH), a tripeptide molecule, is the most abundant nonprotein biothiol in living cells, playing a crucial role in preventing oxidative damage to cellular components and maintaining intracellular redox homeostasis. As a thiol molecule, GSH contains a sulfhydryl (-SH) group that is vital for the body's response to reactive oxygen species (ROS). To confirm whether GSH can be used as a bioindicator or in the early diagnosis of cancers at the cellular level, it is essential to achieve highly selective detection and conjugation of GSH to silicon nanoparticles (SiNPs) under pathological conditions. We are herein excited to report a type of fluorescent ratiometric near-infrared silicon nanoparticle (NIR-SiNP) probe, that is, glutathione peptide conjugated (NIR-SiNPs-GSH), which simultaneously possess small pore sizes at an average of 6.7 nm, an emission of 670 nm, a bioimaging functionality of living cancer cells and animals, and favorable biocompatibility. Taking advantage of these virtues, we further manifest that such resulting NIR-SiNPs, NIR-SiNPs-GSH bioprobes are marvelously worthy for immunofluorescence imaging of cancer cells and living mice. Furthermore, it was shown that DAPI and probes could selectively stain malignant tumor cell nuclei, indicating the possibility for bioimaging and identification of cancer cells and animals. In summary, the suggested NIR-SiNPs-GSH probe has the potential to be a very effective chemical tool for early tumor detection in the future.

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The utilization of axially chiral biaryl diamines has been widely acknowledged as highly advantageous structures for the advancement of chiral catalysts and ligands. This highlights their extensive range of applications in asymmetric catalysis and synthesis. Herein, we devised a direct arylation reactions of 5-aminopyrazoles with azonaphthalenes, utilizing chiral phosphoric acid as the catalyst. This method delivers structurally novel atroposelective N, N-1,2-azole heteroaryl diamines with high yields (up to >98%) and good to excellent enantiomeric ratios while exhibiting a wide range of substrate compatibility.

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BACKGROUND: Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose. METHOD: We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50-55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55-63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS). RESULTS: The median OS was 33.0 months (95% CI: 29.401-36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05). CONCLUSION: HD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn't improve survival but enhances ORR.

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Oral potentially malignant disorders (OPMDs) with genomic alterations have a heightened risk of evolving into oral squamous cell carcinoma (OSCC). Currently, genomic data are typically obtained through invasive tissue biopsy. However, brush biopsy is a non-invasive method that has been utilized for identifying dysplastic cells in OPMD but its effectiveness in reflecting the genomic landscape of OPMDs remains uncertain. This pilot study investigates the potential of brush biopsy samples in accurately reconstructing the genomic profile and tumor evolution in a patient with both OPMD and OSCC. We analyzed single nucleotide variants (SNVs), copy number aberrations (CNAs), and subclonal architectures in paired tissue and brush biopsy samples. The results showed that brush biopsy effectively captured 90% of SNVs and had similar CNA profiles as those seen in its paired tissue biopsies in all lesions. It was specific, as normal buccal mucosa did not share these genomic alterations. Interestingly, brush biopsy revealed shared SNVs and CNAs between the distinct OPMD and OSCC lesions from the same patient, indicating a common ancestral origin. Subclonal reconstruction confirmed this shared ancestry, followed by divergent evolution of the lesions. These findings highlight the potential of brush biopsies in accurately representing the genomic profile of OPL and OSCC, proving insight into reconstructing tumor evolution.

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We aimed to identify dynamic changes of lysine (K)-specific methyltransferase 2A partial tandem duplications (KMT2A-PTD) before and after haploidentical donor hematopoietic stem cell transplantation (HID HSCT) and explore the prognostic value of pre-transplantation levels of KMT2A-PTD in acute myeloid leukemia (AML) receiving HID HSCT. Consecutive 64 AML patients with KMT2A-PTD positivity at diagnosis receiving HID HSCT were included in this study. Patients with KMT2A-PTD ≥1% before HSCT had a slower decrease of KMT2A-PTD after HID HSCT. Patients with KMT2A-PTD ≥1% before HID HSCT had a higher cumulative incidence of relapse (36.4%, 95% confidence interval [CI]: 6.3%-66.5%) at 2 years after HSCT than those with KMT2A-PTD <1% (7.5%, 95% CI: 0.3%-14.7%, P = .010). In multivariable analysis, KMT2A-PTD ≥1% before HID HSCT was the only independent risk factor for relapse (hazard ratio [HR]: 4.90; 95% CI: 1.22-19.59; P = .025). Thus, pre-transplantation levels of KMT2A-PTD could predict relapse in AML patients following HID HSCT.

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Background: Endometrial cancer is one of the most common female cancers globally and in China. Although timely assessment of 5-year relative survival is crucial for guiding secondary prevention and early screening programs for endometrial cancer patients, those kinds of data are scarce in China. We aimed to provide a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from eastern China. Methods: Overall, 945 patients diagnosed with endometrial cancer during 2004 - 2018 from four cancer registries with high-quality data from Taizhou, eastern China were included. Period analysis was used to calculate 5-year relative survival for overall and the stratification by age at diagnosis and region. Model-based period analysis was used to predict the 5-year relative survival for the upcoming period of 2019 - 2023. Results: We found that 5-year relative survival during 2014 - 2018 reached 86.4% for overall, while urban areas had higher survival compared to rural areas (91.3% vs. 85.3%). Furthermore, there was a clear age gradient, decreasing from 89.3% for age < 55 years to 80.5% for age > 74 years. Predicted 5-year relative survival for the upcoming period 2019 - 2023 could reach 88.4%. Conclusions: We provide, a timely and accurate assessment of 5-year relative survival for patients with endometrial cancer from Taizhou, eastern China, reaching 86.4% for overall. Our finding has important implications for the overall evaluation of early detection and screening programs for patients with endometrial cancer in eastern China.

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BACKGROUND: Although colistin is widely recognized as the last line of antibiotics against gram-negative bacteria, the emergence and spread of colistin resistance severely diminish its clinical efficacy and application. An alternative strategy to alleviate this crisis is to identify promising colistin adjuvants with enhanced antibacterial activity. PURPOSE: In this study, the adjuvant effects of paeonol on colistin and the underlying mechanisms were investigated. METHOD: Minimum Inhibitory Concentration (MIC) and checkerboard assays were used to investigate the adjuvant activity and structure-activity relationship of paeonol on the antibacterial effect of colistin in vitro. Time-dependent killing and resistance development assays were used to investigate the bactericidal effects and emergence of colistin resistance. Different fluorescent probes and competitive inhibition tests were used to investigate bacterial membrane functions and potential targets. Skin infection and peritonitis-sepsis models were used to evaluate the combined in vivo effects of colistin and paeonol in vivo. RESULT: Paeonol enhanced the antibacterial effects of colistin against gram-negative bacteria, particularly Klebsiella pneumoniae. Structure-activity relationship analysis showed that the hydroxyl, 4-methoxy and ketone carbonyl side chains of the benzene ring contributed to the adjuvant effect of paeonol. Paeonol enhances the bactericidal effects of colistin and minimizes the emergence of colistin resistance. Notably, mechanistic studies demonstrated that the combination of colistin and paeonol enhances membrane disruption and oxidative damage, possibly via interactions with phosphatidylethanolamine (PE), phosphatidylglycerol (PG), and cardiolipin (CAL). Importantly, paeonol enhanced the efficacy of colistin in both the skin and peritonitis infection models. CONCLUSION: This is the first report on the adjuvant potential of paeonol in colistin to combat K. pneumoniae by promoting membrane disruption and oxidative damage via targeting membrane phospholipids. Notably, the verified target, PE, provides an additional avenue for screening new colistin adjuvants.The combination therapy of paeonol and colistin is a promising strategy for treating infections caused by gram-negative pathogens to address antibiotic resistance issues.

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Precise Couinaud segmentation from preoperative liver computed tomography (CT) is crucial for surgical planning and lesion examination. However, this task is challenging as it is defined based on vessel structures, and there is no intensity contrast between adjacent Couinaud segments in CT images. To solve this challenge, we design a multi-scale point-voxel fusion framework, which can more effectively model the spatial relationship of points and the semantic information of the image, producing robust and smooth Couinaud segmentations. Specifically, we first segment the liver and vessels from the CT image and generate 3D liver point clouds and voxel grids embedded with the vessel structure. Then, our method with two input-specific branches extracts complementary feature representations from points and voxels, respectively. The local attention module adaptively fuses features from the two branches at different scales to balance the contribution of different branches in learning more discriminative features. Furthermore, we propose a novel distance loss at the feature level to make the features in the segment more compact, thereby improving the certainty of segmentation between segments. Our experimental results on three public liver datasets demonstrate that our proposed method outperforms several state-of-the-art methods by large margins. Specifically, in out-of-distribution (OOD) testing of LiTS dataset, our method exceeded the voxel-based 3D UNet by approximately 20% in Dice score, and outperformed the point-based PointNet2Plus by approximately 8% in Dice score. Our code and manual annotations of the public datasets presented in this paper are available online: https://github.com/xukun-zhang/Couinaud-Segmentation.

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The transition from fetal primordial germ cells (PGCs) to spermatogonia (SPG) is critical for male germ cell development; however, the detailed transcriptomic dynamics and regulation underlying this transition remain poorly understood. Here by interrogating the comprehensive transcriptome atlas dataset of mouse male germ cells and gonadal cells development, we elucidated the regulatory networks underlying this transition. Our single-cell transcriptome analysis revealed that the transition from PGCs to SPG was characterized by global hypertranscription. A total of 315 highly active regulators were identified to be potentially involved in this transition, among which a non-transcription factor (TF) regulator TAGLN2 was validated to be essential for spermatogonial stem cells (SSCs) maintenance and differentiation. Metabolism profiling analysis also revealed dynamic changes in metabolism-related gene expression during PGC to SPG transition. Furthermore, we uncovered that intricate cell-cell communication exerted potential functions in the regulation of hypertranscription in germ cells by collaborating with stage-specific active regulators. Collectively, our work extends the understanding of molecular mechanisms underlying male germ cell development, offering insights into the recapitulation of germ cell generation in vitro.