Cryo-electron tomography reveals the microtubule-bound form of inactive LRRK2.

Parkinson's Disease (PD) is the second most common neurodegenerative disorder. Mutations in leucine-rich repeat kinase 2 (LRRK2), a multi-domain protein containing both a kinase and a GTPase, are a leading cause of the familial form of PD. Pathogenic LRRK2 mutations increase LRRK2 kinase activity. While the bulk of LRRK2 is found in the cytosol, the protein associates with membranes where its Rab GTPase substrates are found, and under certain conditions, with microtubules. Integrative structural studies using single-particle cryo-electron microscopy (cryo-EM) and in situ cryo-electron tomography (cryo-ET) have revealed the architecture of microtubule-associated LRRK2 filaments, and that formation of these filaments requires LRRK2's kinase to be in the active-like conformation. However, whether LRRK2 can interact with and form filaments on microtubules in its autoinhibited state, where the kinase domain is in the inactive conformation and the N-terminal LRR domain covers the kinase active site, was not known. Using cryo-ET, we show that full-length LRRK2 can oligomerize on microtubules in its autoinhibited state. Both WT-LRRK2 and PD-linked LRRK2 mutants formed filaments on microtubules. While these filaments are stabilized by the same interfaces seen in the active-LRRK2 filaments, we observed a new interface involving the N-terminal repeats that were disordered in the active-LRRK2 filaments. The helical parameters of the autoinhibited-LRRK2 filaments are different from those reported for the active-LRRK2 filaments. Finally, the autoinhibited-LRRK2 filaments are shorter and less regular, suggesting they are less stable.

Seeing Through Muddy Water: Laser-Induced Graphene for Portable Tomography Imaging.

Due to its outstanding physical and chemical properties, graphene synthesized by laser scribing on polyimide (PI) offers excellent opportunities for photothermal applications, antiviral and antibacterial surfaces, and electrochemical storage and sensing. However, the utilization of such graphene for imaging is yet to be explored. Herein, using chemically durable and electrically conductive laser-induced graphene (LIG) for tomography imaging in aqueous suspensions is proposed. These graphene electrodes are designed as impedance imaging units for four-terminal electrical measurements. Using the real-time portable imaging prototypes, the conductive and dielectric objects can be seen in clear and muddy water with equivalent impedance modeling. This low-cost graphene tomography measurement system offers significant advantages over traditional visual cameras, in which the suspended muddy particles hinder the imaging resolution. This research shows the potential of applying graphene nanomaterials in emerging marine technologies, such as underwater robotics and automatic fisheries.

Non-mydriatic ultra-widefield diffraction-limited retinal imaging.

We demonstrate a new non-mydriatic ultra-widefield optical coherence tomography retinal imaging system, designed with custom optics to improve the imaging field of view, lateral resolution, and patient comfort. The key motivation is to address the challenge with conventional systems that require pupillary dilation, adding time, expense, discomfort, and medical risk to the examination of the retina. Our system provides an ultrawide 100° field of view (beam scanning angle at the scanning pivot point) and maintains a lateral resolution of 20 µm on the center. It also allows a generous working distance of 16 mm, 2-3 times longer than existing ultra-widefield OCT imaging systems. This advanced system was able to avoid iris vignetting artifacts without pharmacological dilation and ensure diffraction-limited ultra-widefield imaging under a generalized eye model. This enables a comprehensive evaluation of retina diseases, especially those affecting the peripheral regions.

Low complexity equalization in coherent optical communication based on Fermat number transform.

In order to reduce the power consumption of digital signal processing (DSP) in a coherent optical communication system, a low complexity equalization scheme in DSP flow of a 400 Gb/s DP-16QAM system has been proposed. This scheme is based on Fermat number transform (FNT), which sequentially performs static equalization (SE) and dynamic equalization (DE) in the transform domain. For different distances, the proposed scheme finds the optimal solution under the condition that transform length and data bit width are mutually restricted under different transmission distances while achieving low complexity and optimal performance. The experimental results show that the adopted transform-domain equalization (TrDE) scheme has much lower computational complexity than the traditional frequency-domain equalization (FDE) and time-domain equalization (TDE) nearly without any performance loss. In the 80, 160, and 240 km scenarios, the number of multiplier is reduced by more than 72%, and the advantage becomes more obvious as the transmission capacity increases.

A novel framework for predicting glacial lake outburst debris flows in the Himalayas amidst climate change.

The retreat of Himalayan glaciers and the expansion of glacial lakes due to global warming have increased the occurrence of glacial lake outburst debris flow (GLODF), posing a serious threat to downstream communities. However, there are gaps in understanding the changes in GLODF occurrence driven by climate change, which challenges disaster management and cross-border cooperation in the Himalayas. To consider this issue, our study presents a novel framework integrating environmental evolution, a process-driven indicator system, and a hybrid machine learning model to predict Himalayan GLODF occurrence in the 21st century. Our findings indicate ongoing temperature (0.27-0.60 °C/10a) and precipitation (1.30-5.00 %/10a) increases under both SSP245 and SSP585 scenarios. Meanwhile, Himalayan glaciers are projected to lose between 70 % and 86 % of their mass by 2100 compared to 2020. Additionally, 2722 ± 207 new glacial lakes are expected to emerge by 2100. GLODF occurrence probability index is anticipated to rise to 1.27-1.30 times the current levels, with the Western Himalayas and Indus basin as high-incidence areas. Currently and in the future, the China-Nepal border remains a hotspot for cross-border GLODF. Our framework offers valuable long-term insights into Himalayan GLODF occurrence trends in response to climate change.

Anterior shoulder dislocation: A bibliometric analysis in the past two decades (2003-2022).

Background: Anterior shoulder dislocation is the most common type of shoulder dislocation and is easy to develop into recurrent type, causing economic burden to society. This study uses the bibliometric method to analyze the global research status, hotspots and trends of anterior shoulder dislocation, aiming to promote the exploration of anterior shoulder dislocation. Methods: The literature on anterior shoulder dislocation in the past two decades were retrieved and downloaded from the Web of Science Core Collection (WOSCC) database. CiteSpace, VOSviewer and bibliometrix package of R software were used to conduct scientific bibliometric analysis of the literature. Finally, some statistical graphics were performed in Graphpad Prism. Results: A total of 3914 publications related to anterior shoulder dislocation from 2003 to 2022 were retrieved and screened from the WOSCC database. The ranking of the analysis results showed that Provencher MT was the author with the highest frequency of occurrence. Rush University was the most notable contributor. The American Journal of Sports Medicine was the most comprehensive journal. The United States was the most prominent country. Keywords related to surgical treatment were more significant than others. Conclusion: In the past two decades, the research output on anterior shoulder dislocation have been increasing year by year. The focus has gradually shifted to surgical treatment. Surgical treatment may continue to be the research hotspots in this field in the future.

Single-cell transcriptomic reveals a cell atlas and diversity of chicken amygdala responded to social hierarchy.

Amygdala serves as a highly cellular, heterogeneous brain region containing excitatory and inhibitory neurons and is involved in the dopamine and serotoninergic neuron systems. An increasing number of studies have revealed the underpinned mechanism mediating social hierarchy in mammal and vertebrate, however, there are rare studies conducted on how amygdala on social hierarchy in poultry. In this study, we conducted food competition tests and determined the social hierarchy of the rooster. We performed cross-species analysis with mammalian amygdala, and found that cell types of human and rhesus monkeys were more closely related and that of chickens were more distant. We identified 26 clusters and divided them into 10 main clusters, of which GABAergic and glutamatergic neurons were associated with social behaviors. In conclusion, our results provide to serve the developmental studies of the amygdala neuron system and new insights into the underpinned mechanism of social hierarchy in roosters.

Ovarian cancer identification technology based on deep learning and second harmonic generation imaging.

Ovarian cancer is among the most common gynecological cancers and the eighth leading cause of cancer-related deaths among women worldwide. Surgery is among the most important options for cancer treatment. During surgery, a biopsy is generally required to screen for lesions; however, traditional case examinations are time consuming and laborious and require extensive experience and knowledge from pathologists. Therefore, this study proposes a simple, fast, and label-free ovarian cancer diagnosis method that combines second harmonic generation (SHG) imaging and deep learning. Unstained fresh human ovarian tissues were subjected to SHG imaging and accurately characterized using the Pyramid Vision Transformer V2 (PVTv2) model. The results showed that the SHG imaged collagen fibers could quantify ovarian cancer. In addition, the PVTv2 model could accurately differentiate the 3240 SHG images obtained from our imaging collection into benign, normal, and malignant images, with a final accuracy of 98.4%. These results demonstrate the great potential of SHG imaging techniques combined with deep learning models for diagnosing the diseased ovarian tissues.

Unique metabolomics characteristics for distinguishing cirrhosis related to different liver diseases: A systematic review and meta-analysis.

BACKGROUND AND AIM: Clinical evidence for early identification and diagnosis of liver cirrhosis (LC) caused by different types of liver disease is limited. We investigated this topic through a meta-analysis of quantitative metabolomics. METHODS: Four databases were searched until October 31, 2022 for studies comparing metabolite levels between patients with different types of liver disease and control individuals. A random-effects model was applied for the meta-analysis. RESULTS: This study included 55 studies with 8266 clinical participants, covering 348 metabolites. In LC related to drug-induced liver injury (DILI), hepatitis B virus (HBV) infection, and non-alcoholic fatty liver disease (NAFLD), the primary bile acid biosynthesis (taurocholic acid: SMD, 1.08[0.81, 1.35]; P < 0.00001; glycocholic acid: SMD, 1.35[1.07, 1.62]; P < 0.00001; taurochenodeoxycholic acid: SMD, 1.36[0.94, 1.78]; P < 0.00001; glycochenodeoxycholic acid: SMD, 1.49[0.93, 2.06]; P < 0.00001), proline and arginine (l-proline: SMD, 1.06[0.53, 1.58]; P < 0.0001; hydroxyproline: SMD, 0.81[0.30, 1.33]; P = 0.002), and fatty acid biosynthesis (palmitic acid: SMD, 0.44[0.21, 0.67]; P = 0.0002; oleic acid: SMD, 0.46[0.19, 0.73]; P = 0.0008; stearic acid: SMD, 0.37[0.07, 0.68]; P = 0.02) metabolic pathways were significantly altered. CONCLUSION: We identified key biomarkers and metabolic characteristics for distinguishing and identifying LC related to different types of liver disease, providing a new perspective for early diagnosis, disease monitoring, and precise treatment.

Primary cilia formation requires the Leigh syndrome-associated mitochondrial protein NDUFAF2.

Mitochondria-related neurodegenerative diseases have been implicated in the disruption of primary cilia function. Mutation in an intrinsic mitochondrial complex I component NDUFAF2 has been identified in Leigh syndrome, a severe inherited mitochondriopathy. Mutations in ARMC9, which encodes a basal body protein, cause Joubert syndrome, a ciliopathy with defects in the brain, kidney, and eye. Here, we report a mechanistic link between mitochondria metabolism and primary cilia signaling. We discovered that loss of NDUFAF2 caused both mitochondrial and ciliary defects in vitro and in vivo and identified NDUFAF2 as a binding partner for ARMC9. We also found that NDUFAF2 was both necessary and sufficient for cilia formation and that exogenous expression of NDUFAF2 rescued the ciliary and mitochondrial defects observed in cells from patients with known ARMC9 deficiency. NAD+ supplementation restored mitochondrial and ciliary dysfunction in ARMC9-deficient cells and zebrafish and ameliorated the ocular motility and motor deficits of a patient with ARMC9 deficiency. The present results provide a compelling mechanistic link, supported by evidence from human studies, between primary cilia and mitochondrial signaling. Importantly, our findings have significant implications for the development of therapeutic approaches targeting ciliopathies.

[The effect of different degrees of Eustachian tube dysfunction on hearing threshold in patients with acquired primary middle ear cholesteatoma after balloon eustachian tuboplasty].

Objective:To investigate the changes in hearing threshold of the acquired primary cholesteatoma of the middle ear with different degrees of eustachian tube dysfunction after balloon eustachian tuboplasty. Methods:This retrospective study included forty cases with middle ear cholesteatoma and eustachian tube dysfunction who underwent open mastoidectomy + tympanoplasty + balloon eustachian tuboplasty were enrolled. All patients were admitted from November 2020 to April 2022. The preoperative eustachian tube score of 0-2 were defined as the lower group, and the scores of 3-5 were defined as the higher group. Pure tone audiometry was measured preoperatively and 1, 3, 6 and 12 months postoperatively. The average value of bone conduction threshold and air conduction threshold of 250-4 000 Hz were calculated, and the air-bone gap was calculated simultaneously. SPSS 25.0 was used for statistical analysis. P<0.05 was considered statistically significant. Results:In the lower group, the air conduction threshold and air-bone gap at 3 months postoperatively were significantly decreased in comparison with those preoperatively（P<0.05），as was the air-bone gap at 6 months postoperatively（P<0.05）. In the higher group, the air conduction threshold and air-bone gap were significantly decreased at 3, 6 and 12 months postoperatively（P<0.05）. Conclusion:The air conduction threshold and air-bone gap of patients with the acquired primary cholesteatoma of the middle ear and eustachian tube dysfunction were significantly decreased after eustachian tube balloon dilatation. Hearing improvement lasted longer in patients with slight eustachian tube dysfunction.

Fecal microbiota transplantation provides insights into the consequences of transcriptome profiles and cell energy in response to circadian misalignment of chickens.

The circadian misalignment (CM) disordered circadian rhythms exert adverse effects on animals. Poultry as one of animals suffers health and welfare problems due to long-term lighting photoperiods caused by CM. However, the roles of CM on organ development, cell growth, metabolism and immune are still unclear in chickens. In this study, a Chinese dual-purpose native breed, was used to explore the effects of CM on transcriptomic pattern of brain and cell energy biogenesis, and further fecal microbiota transplantation (FMT) was applied to investigate its "therapy" effect from CM suffering. Our results showed that the CM led to stunting in brain and small intestine of chicken. CM decreased of cell proliferation, and energy production, mtDNA copies and expression of genes related to cell cycle or mitochondrial biogenetics, while it upregulated the reactive oxygen species (ROS) level and the sensitivity to inflammation. Interestingly, FMT rescued the organ developmental defects and cell dysfunctions induced by CM. Circadian misalignment brought about abnormal tissue and cell developments, energy biogenesis, and immune response in birds. This study provided a comprehensive perspective on understanding the regulation of CM and FMT on bird development and welfare.

Comparative efficacy of exercise modalities for general risk factors, renal function, and physical function in non-dialysis chronic kidney disease patients: a systematic review and network meta-analysis.

BACKGROUND: Exercise therapy can effectively manage chronic kidney disease (CKD) risk factors and improve renal function and physical fitness, but the challenge lies in choosing the right exercise type tailored to patients' condition. METHODS: An electronic search of databases including PubMed, The Cochrane Library, EMBASE, Web of Science, VIP, WanFang, and CNKI was performed. The random effects model was used. Mean difference was employed as the effect size for continuous variables, with 95% confidence interval (CI) provided. RESULTS: A total of 36 RCTs were included in this study. Compared to conventional therapy (CT), the combination of three exercise therapies with CT resulted in notable benefits in enhancing six minutes walk test (6MWT) capacity, 24-h urinary protein quantity (24hUTP), systolic blood pressure (SBP), diastolic blood pressure (DBP). Resistance exercise therapy (RT) + CT were more effective than CT to reduce serum creatinine (Scr), body mass index (BMI), and hemoglobin A1c (HbA1c) and improve estimated glomerular filtration rate (eGFR). In terms of improving peak oxygen uptake (VO2 peak), only two exercise modalities were involved, aerobic exercise therapy (AT) and combined (Resistance-Aerobic) exercise therapy (CBT), both of which were more efficacious than CT. The efficacy ranking overall demonstrated clear benefits for RT in enhancing eGFR and 6MWT, decreasing Scr, BMI, SBP, DBP, and HbA1c, while AT was more suitable for boosting VO2 peak, and CBT had greater potential for reducing 24hUTP. CONSLUSIONS: Exercise therapy combined with CT offers significant advantages over CT in many cases, but no single exercise modality is universally effective for all indicators.

Applications of Biosensors in Bladder Cancer.

Bladder cancer (BC) is the tenth most common cancer globally, predominantly affecting men. Early detection and treatment are crucial due to high recurrence rates and poor prognosis for advanced stages. Traditional diagnostic methods like cystoscopy and imaging have limitations, leading to the exploration of noninvasive methods such as liquid biopsy. This review highlights the application of biosensors in BC, including electrochemical and optical sensors for detecting tumor markers like proteins, nucleic acids, and other biomolecules, noting their clinical relevance. Emerging therapeutic approaches, such as antibody-drug conjugates, targeted therapy, immunotherapy, and gene therapy, are also explored, the role of biosensors in detecting corresponding biomarkers to guide these treatments is examined. Finally, the review addresses the current challenges and future directions for biosensor applications in BC, highlighting the need for large-scale clinical trials and the integration of advanced technologies like deep learning to enhance diagnostic accuracy and treatment efficacy.

A Network of Circular RNA and MicroRNA Sequencing Provides Insights into Pigment Deposition of Changshun Blue Eggshell Chickens.

Eggshell color plays important biological roles and attracts the attention of both egg retailers and researchers. However, whether non-coding RNAs are involved in pigment deposition among different eggshell colors remains unknown. In this study, RNA sequencing was used to analyse the uterine gland transcriptome (CircRNA and miRNA) of Changshun chicken blue-shell hens producing four different eggshell color eggs including dark blue PK(DB) and light blue (LB), dark brown and greenish (between blue and pink, DP) and pink (p). We found that miR-192-x, targeting SLC16a7, was expressed in DB, DP, and LB groups compared with the PK group, which indicates that miR-192-x may play a role in the blue eggshell color. KEGG and GO analyses showed that the "metabolic pathways" with targeted genes such BLVRA and HMOX1 were detected in dark and light blue color eggshell chickens, which confirms the different ratios of biliverdin and HO-1 involved in the deposition of blue color. As annotated by connectivity analysis, RASGRF1 and RASGRF2, belonging to the RASGRF family, are involved in the Ras signaling pathway, which plays an important role in cell growth, differentiation, metastasis and apoptosis. Our findings enrich the database of circRNA, miRNAs and genes for chicken uterine tissue, which will be useful in accelerating molecular selection for blue eggshell color layers.

Radial IR-GRIN lens prepared by multi-temperature fields manipulated gradient crystallization within chalcogenide glass.

Chalcogenide glass has achieved great success in manufacturing axial-type infrared gradient refractive index (IR-GRIN) lenses. However, studies on radial-type IR-GRIN lenses, which are more ideal for optical design, remain rare. The present study introduces what we believe to be a new method for preparing radial IR-GRIN lens by creating high refractive index (n) In2S3 nanocrystals within a 65GeS2-25In2S3-10CsCl (GIC, in molar percentage) glass matrix. Upon introduction of multi-temperature field manipulation, we have successfully achieved central crystallization and simultaneous gradient attenuation spreading toward the edge within GIC glass, providing a radial GRIN profile with Δn over 0.1 while maintaining excellent IR transparency. In addition, the optical and structural properties of the GIC GRIN samples were characterized. The relationship between Raman intensity and the n of glass ceramics at different heat treatment temperatures was investigated, thereby enabling the indirect confirmation of the presence of radial gradient crystallization within the prepared GIC GRIN samples through Raman intensity. Multiple experimental results have shown that this approach has excellent reproducibility and potential for large-scale productions.

Interleukin-22 receptor 1-mediated stimulation of T-type Ca2+ channels enhances sensory neuronal excitability through the tyrosine-protein kinase Lyn-dependent PKA pathway.

BACKGROUND: Interleukin 24 (IL-24) has been implicated in the nociceptive signaling. However, direct evidence and the precise molecular mechanism underlying IL-24's role in peripheral nociception remain unclear. METHODS: Using patch clamp recording, molecular biological analysis, immunofluorescence labeling, siRNA-mediated knockdown approach and behavior tests, we elucidated the effects of IL-24 on sensory neuronal excitability and peripheral pain sensitivity mediated by T-type Ca2+ channels (T-type channels). RESULTS: IL-24 enhances T-type channel currents (T-currents) in trigeminal ganglion (TG) neurons in a reversible and dose-dependent manner, primarily by activating the interleukin-22 receptor 1 (IL-22R1). Furthermore, we found that the IL-24-induced T-type channel response is mediated through tyrosine-protein kinase Lyn, but not its common downstream target JAK1. IL-24 application significantly activated protein kinase A; this effect was independent of cAMP and prevented by Lyn antagonism. Inhibition of PKA prevented the IL-24-induced T-current response, whereas inhibition of protein kinase C or MAPK kinases had no effect. Functionally, IL-24 increased TG neuronal excitability and enhanced pain sensitivity to mechanical stimuli in mice, both of which were suppressed by blocking T-type channels. In a trigeminal neuropathic pain model induced by chronic constriction injury of the infraorbital nerve, inhibiting IL-22R1 signaling alleviated mechanical allodynia, which was reversed by blocking T-type channels or knocking down Cav3.2. CONCLUSION: Our findings reveal that IL-24 enhances T-currents by stimulating IL-22R1 coupled to Lyn-dependent PKA signaling, leading to TG neuronal hyperexcitability and pain hypersensitivity. Understanding the mechanism of IL-24/IL-22R1 signaling in sensory neurons may pave the way for innovative therapeutic strategies in pain management.

Population-wide impact of a pragmatic program to identify and manage individuals at high-risk of cardiovascular disease: a cluster randomized trial in 120 villages from Northern China.

Objectives: To explore the population-wide impacts of an evidence-based high-risk strategy for prevention of cardiovascular diseases in resource-poor populations. Methods: A cluster randomized controlled trial was conducted among 120 villages in rural China, with 60 on intervention and 60 on usual care as controls, for 2 years. The intervention emphasized training village doctors to identify high-risk individuals and administering standardized treatments focusing on hypertension management. A random sample of 20 men aged ≥50 years and 20 women aged ≥60 years was drawn from each village before randomization for the baseline survey, and another independent random sample with the same age and sex distribution was drawn at 2 years for the post-intervention survey. The primary outcome was the population mean systolic blood pressure (SBP). Secondary outcomes included the proportions of patients who received regular primary care, antihypertensive medications, aspirin, or lifestyle advice. Results: A total of 5,654 high cardiovascular risk individuals were identified and managed by village doctors in intervention villages for 15 months on average, with mean SBP lowered by 19.8 mmHg and the proportion with blood pressure under control increased from 22.1% to 72.7%. The primary analysis of the two independent samples (5,050 and 4,887 participants each) showed that population-wide mean SBP in intervention villages did not differ from that in control villages at 2 years (mean difference = 1.0 mmHg, 95% CI: -2.19, 4.26; P = 0.528), though almost all secondary outcomes concerning primary care indicators significantly increased in intervention villages. Conclusions: In our study, the pragmatic cardiovascular risk management program targeting on high-risk individuals significantly improved the quality of primary care. However, its impact on population blood pressure level and the burden of hypertension-related diseases appeared very limited. Clinical Trial Registration: ClinicalTrial.gov identifier, NCT01259700.

The Use of Big Data Analysis in Digital Empowerment of Sustainable Technological Innovation Management of Ecological Enterprises.

With the social economy's rapid progress and the popularization of environmental awareness, ecological enterprises have gradually become a crucial trend in the development of modern enterprises. This work intends to promote the development of ecological enterprises to a higher level. This work first analyzes the management mode of ecological enterprises in the context of big data in China. Then, it establishes various indicators to analyze the role of sustainable technological innovation in enterprise development and the impact of digital empowerment on enterprise development. Finally, this work takes China's manufacturing industry and ecological enterprises in Hubei Province as examples to summarize the digital empowerment of sustainable technological innovation management of ecological enterprises under the background of big data. The final result indicates that sustainable technological innovation significantly reduces ecological enterprises' resource consumption and waste emissions. Additionally, it has a significant positive effect on improving enterprise output value and economic benefits. The digital empowerment of enterprises has a significant driving effect on sustainable technological innovation, with a digital driving coefficient of 26. This work provides a feasible scheme for the specific application of big data analysis in the technology innovation management of ecological enterprises, including market demand analysis, environmental monitoring and governance, technology assessment and risk management. This work expounds the role of big data analysis technology in improving decision-making efficiency, optimizing resource allocation and enhancing the competitiveness of enterprises in the digital empowerment of ecological enterprises.

Development of the second version of Global Prediction System for Epidemiological Pandemic.

Coronavirus disease 2019 (COVID-19) is a severe global public health emergency that has caused a major crisis in the safety of human life, health, global economy, and social order. Moreover, COVID-19 poses significant challenges to healthcare systems worldwide. The prediction and early warning of infectious diseases on a global scale are the premise and basis for countries to jointly fight epidemics. However, because of the complexity of epidemics, predicting infectious diseases on a global scale faces significant challenges. In this study, we developed the second version of Global Prediction System for Epidemiological Pandemic (GPEP-2), which combines statistical methods with a modified epidemiological model. The GPEP-2 introduces various parameterization schemes for both impacts of natural factors (seasonal variations in weather and environmental impacts) and human social behaviors (government control and isolation, personnel gathered, indoor propagation, virus mutation, and vaccination). The GPEP-2 successfully predicted the COVID-19 pandemic in over 180 countries with an average accuracy rate of 82.7%. It also provided prediction and decision-making bases for several regional-scale COVID-19 pandemic outbreaks in China, with an average accuracy rate of 89.3%. Results showed that both anthropogenic and natural factors can affect virus spread and control measures in the early stages of an epidemic can effectively control the spread. The predicted results could serve as a reference for public health planning and policymaking.