Chromatin Accessibility Landscape in Human Early Embryos and Its Association with Evolution.

The dynamics of the chromatin regulatory landscape during human early embryogenesis remains unknown. Using DNase I hypersensitive site (DHS) sequencing, we report that the chromatin accessibility landscape is gradually established during human early embryogenesis. Interestingly, the DHSs with OCT4 binding motifs are enriched at the timing of zygotic genome activation (ZGA) in humans, but not in mice. Consistently, OCT4 contributes to ZGA in humans, but not in mice. We further find that lower CpG promoters usually establish DHSs at later stages. Similarly, younger genes tend to establish promoter DHSs and are expressed at later embryonic stages, while older genes exhibit these features at earlier stages. Moreover, our data show that human active transposons SVA and HERV-K harbor DHSs and are highly expressed in early embryos, but not in differentiated tissues. In summary, our data provide an evolutionary developmental view for understanding the regulation of gene and transposon expression.

Regulatory Innate Lymphoid Cells Control Innate Intestinal Inflammation.

An emerging family of innate lymphoid cells (termed ILCs) has an essential role in the initiation and regulation of inflammation. However, it is still unclear how ILCs are regulated in the duration of intestinal inflammation. Here, we identify a regulatory subpopulation of ILCs (called ILCregs) that exists in the gut and harbors a unique gene identity that is distinct from that of ILCs or regulatory T cells (Tregs). During inflammatory stimulation, ILCregs can be induced in the intestine and suppress the activation of ILC1s and ILC3s via secretion of IL-10, leading to protection against innate intestinal inflammation. Moreover, TGF-ß1 is induced by ILCregs during the innate intestinal inflammation, and autocrine TGF-ß1 sustains the maintenance and expansion of ILCregs. Therefore, ILCregs play an inhibitory role in the innate immune response, favoring the resolution of intestinal inflammation.

IL-13 secreted by ILC2s promotes the self-renewal of intestinal stem cells through circular RNA circPan3.

Intestinal stem cells (ISCs) are maintained by stemness signaling for precise modulation of self-renewal and differentiation under homeostasis. However, the way in which intestinal immune cells regulate the self-renewal of ISCs remains elusive. Here we found that mouse and human Lgr5+ ISCs showed high expression of the immune cell-associated circular RNA circPan3 (originating from the Pan3 gene transcript). Deletion of circPan3 in Lgr5+ ISCs impaired their self-renewal capacity and the regeneration of gut epithelium in a manner dependent on immune cells. circPan3 bound mRNA encoding the cytokine IL-13 receptor subunit IL-13Rα1 (Il13ra1) in ISCs to increase its stability, which led to the expression of IL-13Rα1 in ISCs. IL-13 produced by group 2 innate lymphoid cells in the crypt niche engaged IL-13Rα1 on crypt ISCs and activated signaling mediated by IL-13‒IL-13R, which in turn initiated expression of the transcription factor Foxp1. Foxp1 is associated with ß-catenin in rendering its nuclear translocation, which caused activation of the ß-catenin pathway and the maintenance of Lgr5+ ISCs.

Intestinal Tuft-2 cells exert antimicrobial immunity via sensing bacterial metabolite N-undecanoylglycine.

Tuft cells are a type of intestinal epithelial cells that exist in epithelial barriers and play a critical role in immunity against parasite infection. It remains insufficiently clear whether Tuft cells participate in bacterial eradication. Here, we identified Sh2d6 as a signature marker for CD45+ Tuft-2 cells. Depletion of Tuft-2 cells resulted in susceptibility to bacterial infection. Tuft-2 cells quickly expanded in response to bacterial infection and sensed the bacterial metabolite N-undecanoylglycine through vomeronasal receptor Vmn2r26. Mechanistically, Vmn2r26 engaged with N-undecanoylglycine activated G-protein-coupled receptor-phospholipase C gamma2 (GPCR-PLCγ2)-Ca2+ signaling axis, which initiated prostaglandin D2 (PGD2) production. PGD2 enhanced the mucus secretion of goblet cells and induced antibacterial immunity. Moreover, Vmn2r26 signaling also promoted SpiB transcription factor expression, which is responsible for Tuft-2 cell development and expansion in response to bacterial challenge. Our findings reveal an additional function of Tuft-2 cells in immunity against bacterial infection through Vmn2r26-mediated recognition of bacterial metabolites.

The ER membrane adaptor ERAdP senses the bacterial second messenger c-di-AMP and initiates anti-bacterial immunity.

Cyclic diadenylate monophosphate (c-di-AMP) is secreted by bacteria as a secondary messenger. How immune cells detect c-di-AMP and initiate anti-bacterial immunity remains unknown. We found that the endoplasmic reticulum (ER) membrane adaptor ERAdP acts as a direct sensor for c-di-AMP. ERAdP-deficient mice were highly susceptible to Listeria monocytogenes infection and exhibited reduced pro-inflammatory cytokines. Mechanistically, c-di-AMP bound to the C-terminal domain of ERAdP, which in turn led to dimerization of ERAdP, resulting in association with and activation of the kinase TAK1. TAK1 activation consequently initiated activation of the transcription factor NF-κB to induce the production of pro-inflammatory cytokines in innate immune cells. Moreover, double-knockout of ERAdP and TAK1 resulted in heightened susceptibility to L. monocytogenes infection. Thus, ERAdP-mediated production of pro-inflammatory cytokines is critical for controlling bacterial infection.

Long noncoding RNA lncKdm2b is required for ILC3 maintenance by initiation of Zfp292 expression.

Innate lymphoid cells (ILCs) communicate with other hematopoietic and nonhematopoietic cells to regulate immunity, inflammation and tissue homeostasis. How ILC lineages develop and are maintained remains largely unknown. In this study we observed that a divergent long noncoding RNA (lncRNA), lncKdm2b, was expressed at high levels in intestinal group 3 ILCs (ILC3s). LncKdm2b deficiency in the hematopoietic system led to reductions in the number and effector functions of ILC3s. LncKdm2b expression sustained the maintenance of ILC3s by promoting their proliferation through activation of the transcription factor Zfp292. Mechanistically, lncKdm2b recruited the chromatin organizer Satb1 and the nuclear remodeling factor (NURF) complex onto the Zfp292 promoter to initiate its transcription. Deletion of Zfp292 or Bptf also abrogated the maintenance of ILC3s, leading to susceptibility to bacterial infection. Therefore, our findings reveal that lncRNAs may represent an additional layer of regulation of ILC development and function.

Glutamylation of the DNA sensor cGAS regulates its binding and synthase activity in antiviral immunity.

Cyclic GMP-AMP synthase (cGAS) senses cytosolic DNA during viral infection and catalyzes synthesis of the dinucleotide cGAMP, which activates the adaptor STING to initiate antiviral responses. Here we found that deficiency in the carboxypeptidase CCP5 or CCP6 led to susceptibility to DNA viruses. CCP5 and CCP6 were required for activation of the transcription factor IRF3 and interferons. Polyglutamylation of cGAS by the enzyme TTLL6 impeded its DNA-binding ability, whereas TTLL4-mediated monoglutamylation of cGAS blocked its synthase activity. Conversely, CCP6 removed the polyglutamylation of cGAS, whereas CCP5 hydrolyzed the monoglutamylation of cGAS, which together led to the activation of cGAS. Therefore, glutamylation and deglutamylation of cGAS tightly modulate immune responses to infection with DNA viruses.

Noncoding RNA circBtnl1 suppresses self-renewal of intestinal stem cells via disruption of Atf4 mRNA stability.

Intestinal stem cells (ISCs) at the crypt base are responsible for the regeneration of the intestinal epithelium. However, how ISC self-renewal is regulated still remains unclear. Here we identified a circular RNA, circBtnl1, that is highly expressed in ISCs. Loss of circBtnl1 in mice enhanced ISC self-renewal capacity and epithelial regeneration, without changes in mRNA and protein levels of its parental gene Btnl1. Mechanistically, circBtnl1 and Atf4 mRNA competitively bound the ATP-dependent RNA helicase Ddx3y to impair the stability of Atf4 mRNA in wild-type ISCs. Furthermore, ATF4 activated Sox9 transcription by binding to its promoter via a unique motif, to enhance the self-renewal capacity and epithelial regeneration of ISCs. In contrast, circBtnl1 knockout promoted Atf4 mRNA stability and enhanced ATF4 expression, which caused Sox9 transcription to potentiate ISC stemness. These data indicate that circBtnl1-mediated Atf4 mRNA decay suppresses Sox9 transcription that negatively modulates self-renewal maintenance of ISCs.

Rapid characterization of anti-CRISPR proteins and optogenetically engineered variants using a versatile plasmid interference system.

Anti-CRISPR (Acr) proteins are encoded by mobile genetic elements to overcome the CRISPR immunity of prokaryotes, displaying promises as controllable tools for modulating CRISPR-based applications. However, characterizing novel anti-CRISPR proteins and exploiting Acr-related technologies is a rather long and tedious process. Here, we established a versatile plasmid interference with CRISPR interference (PICI) system in Escherichia coli for rapidly characterizing Acrs and developing Acr-based technologies. Utilizing the PICI system, we discovered two novel type II-A Acrs (AcrIIA33 and AcrIIA34), which can inhibit the activity of SpyCas9 by affecting DNA recognition of Cas9. We further constructed a circularly permuted AcrIIA4 (cpA4) protein and developed optogenetically engineered, robust AcrIIA4 (OPERA4) variants by combining cpA4 with the light-oxygen-voltage 2 (LOV2) blue light sensory domain. OPERA4 variants are robust light-dependent tools for controlling the activity of SpyCas9 by approximately 1000-fold change under switching dark-light conditions in prokaryotes. OPERA4 variants can achieve potent light-controllable genome editing in human cells as well. Together, our work provides a versatile screening system for characterizing Acrs and developing the Acr-based controllable tools.

The chromatin remodeler SRCAP promotes self-renewal of intestinal stem cells.

Lgr5+ intestinal stem cells (ISCs) exhibit self-renewal and differentiation features under homeostatic conditions, but the mechanisms controlling Lgr5 + ISC self-renewal remain elusive. Here, we show that the chromatin remodeler SRCAP is highly expressed in mouse intestinal epithelium and ISCs. Srcap deletion impairs both self-renewal of ISCs and intestinal epithelial regeneration. Mechanistically, SRCAP recruits the transcriptional regulator REST to the Prdm16 promoter and induces expression of this transcription factor. By activating PPARδ expression, Prdm16 in turn initiates PPARδ signaling, which sustains ISC stemness. Rest or Prdm16 deficiency abrogates the self-renewal capacity of ISCs as well as intestinal epithelial regeneration. Collectively, these data show that the SRCAP-REST-Prdm16-PPARδ axis is required for self-renewal maintenance of Lgr5 + ISCs.

Regulatory function and mechanism research for m6A modification WTAP via SUCLG2-AS1- miR-17-5p-JAK1 axis in AML.

Acute myeloid leukemia (AML), characterized by the abnormal accumulation of immature marrow cells in the bone marrow, is a malignant tumor of the blood system. Currently, the pathogenesis of AML is not yet clear. Therefore, this study aims to explore the mechanisms underlying the development of AML. Firstly, we identified a competing endogenous RNA (ceRNA) SUCLG2-AS1-miR-17-5p-JAK1 axis through bioinformatics analysis. Overexpression of SUCLG2-AS1 inhibits proliferation, migration and invasion and promotes apoptosis of AML cells. Secondly, luciferase reporter assay and RIP assay validated that SUCLG2-AS1 functioned as ceRNA for sponging miR-17-5p, further leading to JAK1 underexpression. Additionally, the results of MeRIP-qPCR and m6A RNA methylation quantification indicted that SUCLG2-AS1(lncRNA) had higher levels of m6A RNA methylation compared with controls, and SUCLG2-AS1 is regulated by m6A modification of WTAP in AML cells. WTAP, one of the main regulatory components of m6A methyltransferase complexes, proved to be highly expressed in AML and elevated WTAP is associated with poor prognosis of AML patients. Taken together, the WTAP-SUCLG2-AS1-miR-17-5p-JAK1 axis played essential roles in the process of AML development, which provided a novel therapeutic target for AML.

Visual deterioration outcomes following optic pathway glioma treatment: a 12-year single institution retrospective study.

OBJECTIVE: The surgical treatment of optic pathway gliomas (OPG) remains controversial, with visual outcomes often unpredictable. The present study explored surgical and clinical factors influencing visual acuity (VA) after OPG treatment and developed anatomical subtypes correlated with clinical symptoms. METHODS: Children with OPG who underwent initial partial tumor resection at Beijing Tiantan Hospital from January 2011 to December 2022 were retrospectively analyzed. Multivariate logistic regression and random forest analyses were performed to identify risk factors for post-treatment VA deterioration and a decision tree model was created based on significant factors. RESULTS: A total of 140 patients were enrolled. Multivariate logistic regression analysis identified surgical approach and initial VA as independent predictors of post-treatment VA deterioration (P < 0.05). Surgical approach, initial VA, and extent of tumor resection were the most significant factors for risk assessment and were included in the decision tree model, with surgical approach as the most important "root" node. The model demonstrated good predictive performance, with area under the curve values of 0.75 and 0.66 for the training and test datasets, respectively. A simple anatomical classification was developed, which revealed clinical characteristic differences among OPG types. Meanwhile, a correlation analysis of post-treatment visual deterioration was performed for each of the three anatomical types. CONCLUSION: This study offers a predictive model for visual outcomes following initial tumor-reduction surgery in OPG patients, which may help in visual outcomes risk stratification. Additionally, the anatomical classification effectively indicates OPG growth direction, offering potential insights into clinical symptoms.

Occurrence of Chlorinated Derivatives of Bisphenol S in Paper Products and Their Potential Health Risks through Dermal Exposure.

The occurrence of chlorinated derivatives of bisphenol S (Clx-BPS) and BPS was investigated in nine types of paper products (n = 125), including thermal paper, corrugated boxes, mail envelopes, newspapers, flyers, magazines, food contact paper, household paper, and business cards. BPS was found in all paper product samples, while Clx-BPS were mainly found in thermal paper (from below the limit of detection (

Temperature-dependent decomposition of the CL-20/MTNP cocrystal after phase separation.

CL-20 (2,4,6,8,10,12-hexanitro-2,4,6,8,10,12-hexaazaisowurtzitane)-based cocrystals are attractive energetic cocrystals with a potential for high energy and low sensitivity, which account for nearly one-third of energetic cocrystals. The applications of cocrystal explosives require in-depth understanding of their thermal kinetics behaviors. Although thermal kinetics of the decomposition of CL-20-based cocrystals having no melting point have been studied, relevant research of CL-20-based cocrystals having a melting point, which are also the most frequently observed type, is still rare. In this study, the CL-20/MTNP (1-methyl-3,4,5-trinitropyrazole) cocrystal was chosen as a typical CL-20-based cocrystal having a melting point to investigate its thermal kinetics behavior. The thermal decomposition of CL-20/MTNP was identified to be a typical heterogeneous reaction with phase separation before decomposition. Due to the presence of intermolecular hydrogen bonds between CL-20 and molten MTNP after phase separation, the thermal decomposition behavior of CL-20/MTNP was strongly temperature-dependent. The complex decomposition reaction was separated into its three constituent pathways to simplify the kinetic analysis. On the basis of in-depth understanding of the decomposition process, the best functions of mechanism and kinetic parameters for each process of CL-20/MTNP decomposition were obtained using the model-fitting method. Finally, important thermal safety indicators, such as TMRad and SADT were simulated by combining the established kinetic models. This study provides further insights into the entire reaction process of the CL-20/MTNP cocrystal and would help in its better applications.

Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge Dysidea arenaria.

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (1-6), were isolated from the marine sponge Dysidea arenaria collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A (1) features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (2-4) possess two rare secomeroterpene scaffolds. Arenarialins A-F showed inhibitory activity on the production of inflammatory cytokines TNF-α and IL-6 in LPS-induced RAW264.7 macrophages with arenarialin D regulating the NF-κB/MAPK signaling pathway.

Lumen-apposing metal stents versus traditional self-expanding metal stents for endoscopic ultrasound-guided drainage of pancreatic fluid collections: a systematic review and meta-analysis.

BACKGROUND: Endoscopic drainage has become the preferred treatment for pancreatic fluid collections (PFCs). There is still a lack of reliable evidence to prove which metal stent is the best choice for endoscopic ultrasound (EUS)-guided drainage of PFCs. In this study, we aimed to evaluate the efficacy and safety of lumen-apposing metal stents (LAMS) compared to traditional self-expanding metal stents (SEMS) in meta-analysis. METHODS: We systematically searched PubMed, Embase, Web of Science, and Cochrane Library up to July 15, 2023. Relevant publications that compared LAMS with traditional SEMS for drainage of patients' PFCs under EUS-guidance were included. This meta-analysis assessed endpoints using Review Manager 5.3 and Stata 14.0 statistical software. RESULT: Nine citations comprising 707 patients with PFCs were included. The clinical success rate of LAMS tended to be higher than that of SEMS (RR = 1.07, 95%CI [1.00, 1.15], P = 0.05). LAMS had a lower technical success rate (RR = 0.97, 95%CI [0.94, 0.99], P = 0.02) and faster procedure time (minutes) (MD = - 24.29, 95%CI [- 25.59, - 22.99], P < 0.00001) compared to SEMS. In addition, LAMS had fewer overall adverse events (RR = 0.64, 95%CI [0.48, 0.87], P = 0.004). For specific adverse events, LAMS had fewer migration (RR = 0.37, 95%CI [0.19, 0.72], P = 0.003), occlusion (RR = 0.43, 95%CI [0.22, 0.82], P = 0.01) and infection (RR = 0.38, 95%CI [0.20, 0.70], P = 0.002). There was no significant difference in bleeding and perforation between the two stents. For hospital stay (days), LAMS group was similar to SEMS group (MD = - 3.34, 95%CI [- 7.71, - 1.03], P = 0.13). Regarding recurrence, LAMS group was fewer than SEMS group (RR = 0.41, 95%CI [0.21, 0.78], P = 0.007). CONCLUSION: Compared to traditional SEMS, LAMS has a higher clinical success rate, faster procedure time, fewer adverse events, similar hospital stay and lower recurrence rate in EUS-guided drainage of PFCs. LAMS is a good choice with a high technical success rate over 95%, and using a shorter length or "one-step" operation can further improve it. Richer placement experience is required for LAMS placement under EUS-guidance.

Association between City-Level Particulate Matter Exposure and Frailty among Middle-Aged and Older Adults in China.

INTRODUCTION: The effects of exposure to particulate matter and frailty, as well as its exposure-response relationship, have not been effectively explored. This study aimed to explore the association between long-term exposure to particulate matter and frailty state and each dimension in Chinese middle-aged and older adults, in addition to the exposure-response relationship. METHODS: The data were obtained from the National Urban Air Quality Real-Time Dissemination Platform and China Health and Retirement Longitudinal Study (CHARLS). Frailty was measured by a frailty index containing 39 indicators. Annual averages of seven pollutants were calculated from hourly monitoring data. We used multilevel regression modeling to explore the association between long-term exposure to particulate matter and frailty. Meanwhile, we explored the exposure-response relationship based on a multilevel generalized summation model. We performed a sensitivity analysis using a multi-pollution model and a quantile-based g-computation (QGC) model. RESULTS: A total of 15,611 participants were included in the analysis. We find that long-term exposure to PM2.5 was associated with an increased risk of pre-frailty and frailty (all p < 0.05). PMc and PM10 exhibited similar associations. The exposure-response relationship between PM2.5 showed a linear relationship, whereas the exposure-response relationship between PM10, PMc showed a nonlinear relationship. Elevated PM2.5 concentrations showed significant positive associations with the number of chronic disease score, IADL score, and functional limitation status score (all p < 0.05). PM10 and PMc showed similar positive correlations. These results remained robust after sensitivity analyses using a multi-pollution model and QGC model. CONCLUSION: Chronic exposure to particulate matter was significantly associated with increased risk of frailty. The exposure-response relationship between PM2.5 concentration and frailty showed a linear relationship, and the exposure-response relationship between PM10 and PMc showed a nonlinear relationship. Exposure to a mixture of pollutants carried a higher risk of frailty than exposure to a single pollutant.

Discovery of potent and versatile CRISPR-Cas9 inhibitors engineered for chemically controllable genome editing.

Anti-CRISPR (Acr) proteins are encoded by many mobile genetic elements (MGEs) such as phages and plasmids to combat CRISPR-Cas adaptive immune systems employed by prokaryotes, which provide powerful tools for CRISPR-Cas-based applications. Here, we discovered nine distinct type II-A anti-CRISPR (AcrIIA24-32) families from Streptococcus MGEs and found that most Acrs can potently inhibit type II-A Cas9 orthologs from Streptococcus (SpyCas9, St1Cas9 or St3Cas9) in bacterial and human cells. Among these Acrs, AcrIIA26, AcrIIA27, AcrIIA30 and AcrIIA31 are able to block Cas9 binding to DNA, while AcrIIA24 abrogates DNA cleavage by Cas9. Notably, AcrIIA25.1 and AcrIIA32.1 can inhibit both DNA binding and DNA cleavage activities of SpyCas9, exhibiting unique anti-CRISPR characteristics. Importantly, we developed several chemically inducible anti-CRISPR variants based on AcrIIA25.1 and AcrIIA32.1 by comprising hybrids of Acr protein and the 4-hydroxytamoxifen-responsive intein, which enabled post-translational control of CRISPR-Cas9-mediated genome editing in human cells. Taken together, our work expands the diversity of type II-A anti-CRISPR families and the toolbox of Acr proteins for the chemically inducible control of Cas9-based applications.

Cu exposure induces liver inflammation via regulating gut microbiota/LPS/liver TLR4 signaling axis.

Copper (Cu) serves as an essential cofactor in all organisms, yet excessive Cu exposure is widely recognized for its role in inducing liver inflammation. However, the precise mechanism by which Cu triggers liver inflammation in ducks, particularly in relation to the interplay in gut microbiota regulation, has remained elusive. In this investigation, we sought to elucidate the impact of Cu exposure on liver inflammation through gut-liver axis in ducks. Our findings revealed that Cu exposure markedly elevated liver AST and ALT levels and induced liver inflammation through upregulating pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) and triggering the LPS/TLR4/NF-κB signaling pathway. Simultaneously, Cu exposure induced alterations in the composition of intestinal flora communities, notably increasing the relative abundance of Sphingobacterium, Campylobacter, Acinetobacter and reducing the relative abundance of Lactobacillus. Cu exposure significantly decreased the protein expression related to intestinal barrier (Occludin, Claudin-1 and ZO-1) and promoted the secretion of intestinal pro-inflammatory cytokines. Furthermore, correlation analysis was observed that intestinal microbiome and gut barrier induced by Cu were closely related to liver inflammation. Fecal microbiota transplantation (FMT) experiments further demonstrated the microbiota-depleted ducks transplanting fecal samples from Cu-exposed ducks disturbed the intestinal dysfunction, which lead to impaire liver function and activate the liver inflammation. Our study provided insights into the mechanism by which Cu exposure induced liver inflammation in ducks through the regulation of gut-liver axis. These results enhanced our comprehension of the potential mechanisms driving Cu-induced hepatotoxicity in avian species.

Spatial and temporal differentiation and its driving factors of air quality in the economic circle of Shandong Province during 2013-2020.

As the negative repercussions of environmental devastation, such as air quality decline and air pollution, become more apparent, environmental consciousness is growing across the world, forcing nations to take steps to mitigate the damage. China pledged to achieve air quality improvement goal to combat global environment issue, yet the spatial-temporal differentiation and its driving factors of environment-meteorology-economic index for air quality are not fully analysed. To promote regional collaborative control of air pollution and achieve sustainable urban development, spatial and temporal different and its driving factors of air quality in Shandong Province during 2013-2020. Results revealed that concentrations of sulfur dioxide (SO2), nitrogen dioxide (NO2), particulate matter 2.5 (PM2.5), particulate matter 10 (PM10), and carbon monoxide (CO-95per) exhibited decreasing trend (SO2 concentrations decreasing 84 % and CO-95per concentrations decreasing 90 %). Air quality was improved from inland areas to coastal areas. Pollutant indicators of SO2, NO2, PM10, PM2.5, and CO-95per demonstrated significant positive correlation (P < 0.05). Air temperature and precipitation are significantly negatively correlated with concentrations of SO2, NO2, PM10, PM2.5, and CO-95per but significantly positively correlated with ozone (O3-8 h). SO2, NO2, PM2.5, PM10, CO-95per, and proportion of days with heavy pollution are strongly positively correlated with proportion of secondary industry but strongly negatively correlated with proportion of tertiary industry and volume of household waste. Except for O3-8 h, pollutant index of Provincial Capital Economic Circle (PCEC) and Southern Shandong Economic Circle (SSEC) has significant negative correlation (P < 0.05) with regional gross domestic product and investment in environmental protection; however, investment in environmental protection of Eastern Shandong Economic Circle (ESEC) has no significant correlation with air pollution index. There was significant negative correlation between vegetable sowing area and SSEC pollutant index. The relationship between pollution emission and investment in environmental protection has shifted from high pollution-low investment to low pollution-low investment in PCEC, ESEC and SSEC, and the inflection point was in 2020 for PCEC, 2019 for ESEC, and 2020 for SSEC. Those results provide empirical evidence and theoretical support for the improvement of regional air quality, aiming to achieve high-quality development. According to these findings, it has been found that meteorological elements, pollutant emission, socio-economic factors and agricultural data affect air quality. Those results could provide meaningful and significant supporting for synergistic regulation of diverse pollutants.