Comparative effectiveness of neoadjuvant chemotherapy plus surgery versus concurrent chemoradiotherapy in stages IB2 to IIB of cervical cancer: a meta-analysis.

Objectives: To assess the comparative efficacy of neoadjuvant chemotherapy followed by surgery (NACT+S) versus concurrent chemoradiotherapy (CCRT) for patients with cervical cancer stages IB2 to IIB. Method: An exhaustive literature search was conducted up to November 2023 in databases including PubMed, Embase, Web of Science, and the Cochrane Library, focusing on disease-free survival (DFS) and overall survival (OS). Data were analyzed using STATA version 15. Results: The meta-analysis included data from two randomized controlled trials and eight retrospective cohort studies, totaling 2,879 patients with stages IB2 to IIB cervical cancer. Pooled data showed no significant difference in OS [hazard ratio (HR) 0.71, 95% confidence interval (CI): 0.51 to 1.00, p = 0.052] and DFS (HR 0.65, 95% CI: 0.38 to 1.14, p = 0.132) between NACT+S and CCRT. Subgroup analysis revealed that NACT+S provided a better OS in Asian populations, retrospective cohort studies, TP regimen chemotherapy, and multivariate analysis. Conclusion: The findings indicate that CCRT and NACT+S are comparably effective for treating cervical cancer stages IB2 to IIB. Notably, in specific subgroups such as Asian patients and those receiving the TP regimen, NACT+S appears to enhance OS.

Transcription factor OsbZIP10 modulates rice grain quality by regulating OsGIF1.

Understanding and optimizing the process of grain filling helps the quest to maximize rice (Oryza sativa L.) seed yield and quality, yet the intricate mechanisms at play remain fragmented. Transcription factors (TFs) are major players in the gene networks underlying the grain filling process. Here, we employed grain incomplete filling (OsGIF1)/cell wall invertase 2, a key gene involved in grain filling, to explore its upstream TFs and identified a bZIP family TF, OsbZIP10, to be a transcriptional activator of OsGIF1. Rice grains of the knockouts of OsbZIP10 showed increased white-core rates but lower amylose content (AC), leading to better eating and cooking qualities in all genetic backgrounds investigated, though the impact of mutations in OsbZIP10 on grain weight depended on genetic background. Multi-omics analyses suggested that, in addition to OsGIF1, multiple genes involved in different biological processes contributing to grain filling were targeted by OsbZIP10, including OsAGPS1, a gene encoding the ADP-Glc pyrophosphorylase (AGPase) small subunit, and genes contributing to homeostasis of reactive oxygen species. Distinct genetic make-up was observed in OsbZIP10 between japonica and indica rice varieties, with the majority varieties of each subspecies belonging to two different haplotypes that were closely associated with AC. Overexpressing the haplotype linked to high-AC in the low-AC genetic background increased AC. Overall, this study sheds crucial light on the significance of the OsbZIP10-OsGIF1 module in the determination of rice grain quality, offering a potential avenue for genetic engineering of rice to produce seeds with tailored attributes.

Learning Molecular Representation in a Cell.

Predicting drug efficacy and safety in vivo requires information on biological responses (e.g., cell morphology and gene expression) to small molecule perturbations. However, current molecular representation learning methods do not provide a comprehensive view of cell states under these perturbations and struggle to remove noise, hindering model generalization. We introduce the Information Alignment (InfoAlign) approach to learn molecular representations through the information bottleneck method in cells. We integrate molecules and cellular response data as nodes into a context graph, connecting them with weighted edges based on chemical, biological, and computational criteria. For each molecule in a training batch, InfoAlign optimizes the encoder's latent representation with a minimality objective to discard redundant structural information. A sufficiency objective decodes the representation to align with different feature spaces from the molecule's neighborhood in the context graph. We demonstrate that the proposed sufficiency objective for alignment is tighter than existing encoder-based contrastive methods. Empirically, we validate representations from InfoAlign in two downstream tasks: molecular property prediction against up to 19 baseline methods across four datasets, plus zero-shot molecule-morphology matching.

A National Study Exploring the Association between Fasting Duration and Mortality among the Elderly.

(1) Background: The benefits of weight management are widely recognized, and prolonged fasting duration has become a common method for weight control. The suitability of time-restricted eating (TRE) for elderly individuals remains controversial. This study aims to examine the correlation between fasting duration and mortality within a nationally representative cohort of elderly individuals in the United States. (2) Methods: Data were extracted from a prospective cohort study conducted as part of the National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018. Participants aged over 60 with complete data on dietary intake and mortality follow-up information were included. Fasting duration was assessed using two 24 h dietary recalls. All the participants were categorized into fasting duration quartiles. Mortality outcomes were ascertained through the National Death Index. Cox proportional hazards regression models were utilized to analyze the association between fasting duration and mortality. (3) Results: The final analysis included 10,561 elderly participants (mean age 69.89, 45.58% male). Individuals with the longest fasting duration (over 12.38 h) had a significantly higher risk of CVD mortality compared to those with a normal fasting duration (10.58-12.38 h). This elevated CVD mortality risk was particularly pronounced in males, individuals over 70 years old, and non-shift workers. A non-linear relationship was observed between fasting duration and all-cause mortality and CVD mortality. (4) Conclusions: Prolonged fasting periods are associated with a higher risk of CVD mortality in the elderly population, although this correlation is not evident for all-cause, cancer, or other-cause mortality. A fasting duration of 11.49 h correlates with the lowest mortality risk. Additionally, elderly individuals with the shortest fasting duration exhibit elevated hazard ratios for both cancer and other-cause mortality. As with any health intervention, clinicians should exercise caution when recommending a fasting regimen that is personalized to the health condition of people who are older. Further research through randomized controlled trials should be conducted to comprehensively investigate the impact of TRE on mortality.

Integrating network pharmacology and experimental models to investigate the efficacy and mechanism of Tiansha mixture on xerosis.

Epidermal Growth Factor Receptor Inhibitors (EGFRIs) is a common cancer therapy, but they occasionally cause severe side effects such as xerosis. Tiansha mixture (TM), a traditional Chinese medicines formulation, is develpoed to treat xerosis. This study aims to understand mechanisms of TM on xerosis. Bio-active compounds were selected from databases (TCMSP, TCM-ID, HERB, ETCM) and removed for poor oral bioavailability and low drug likeness. Then a network-based approach filtered out potential active compounds against xerosis. KEGG enrichment analysis identified PI3K/AKT and ERK/MAPK pathways, which were further verified by molecular docking. Afterwards, the effect of TM on activation of PI3K/AKT and ERK/MAPK pathways was validated in gefitinib-induced xerosis rats, where AKT-activator SC79 and MAPK-activator CrPic were also applied. Skin damage was assessed by dorsal score and HE and Tunel stainings. the levels of inflammation factors IL-6 and TNF-α in serum and skin tissue were measured by ELISA. Western blot was used to detect protein levels in the pathways. Network pharmacology identified 111 bio-active compounds from TM and 14 potential targets. Docking simulation showed apigenin, luteolin, and quercetin bio-active compounds in TM bound to IKBKG, INSR, and RAF-1 proteins. In xerosis model rats, TM mitigated xerosis damage, decreased inflammation factors, and phosphorylation of PI3K/AKT and ERK/MAPK proteins. SC79 or CrPic or their combination reversed TM's effect. The current study identified potential targets and PI3K/AKT and ERK/MAPK pathways involved in the effect of TM on xerosis, thus providing a foundation for TM clinical application.

Triptolide decreases podocytes permeability by regulating TET2-mediated hydroxymethylation of ZO-1.

Podocyte injury or dysfunction can lead to proteinuria and glomerulosclerosis. Zonula occludens 1 (ZO-1) is a tight junction protein which connects slit diaphragm (SD) proteins to the actin cytoskeleton. Previous studies have shown that the expression of ZO-1 is decreased in chronic kidney disease (CKD). Thus, elucidation of the regulation mechanism of ZO-1 has considerable clinical importance. Triptolide (TP) has been reported to exert a strong antiproteinuric effect by inhibiting podocyte epithelial mesenchymal transition (EMT) and inflammatory response. However, the underlying mechanisms are still unclear. We found that TP upregulates ZO-1 expression and increases the fluorescence intensity of ZO-1 in a puromycin aminonucleoside (PAN)-induced podocyte injury model. Permeablity assay showed TP decreases podocyte permeability in PAN-treated podocyte. TP also upregulates the DNA demethylase TET2. Our results showed that treatment with the DNA methyltransferase inhibitors 5-azacytidine (5-AzaC) and RG108 significantly increased ZO-1 expression in PAN-treated podocytes. Methylated DNA immunoprecipitation (MeDIP) and hydroxymethylated DNA immunoprecipitation (hMeDIP) results showed that TP regulates the methylation status of the ZO-1 promoter. Knockdown of TET2 decreased ZO-1 expression and increased methylation of its promoter, resulting in the increase of podocyte permeability. Altogether, these results indicate that TP upregulates the expression of ZO-1 and decreases podocyte permeability through TET2-mediated 5 mC demethylation. These findings suggest that TP may alleviate podocyte permeability through TET2-mediated hydroxymethylation of ZO-1.

Activation of TAS2R4 signaling attenuates podocyte injury induced by high glucose.

Bitter taste receptors (TAS2Rs) Tas2r108 gene possesses a high abundance in mouse kidney; however, the biological functions of Tas2r108 encoded receptor TAS2Rs member 4 (TAS2R4) are still unknown. In the present study, we found that mouse TAS2R4 (mTAS2R4) signaling was inactivated in chronic high glucose-stimulated mouse podocyte cell line MPC, evidenced by the decreased protein expressions of mTAS2R4 and phospholipase C ß2 (PLCß2), a key downstream molecule of mTAS2R4 signaling. Nonetheless, agonism of mTAS2R4 by quinine recovered mTAS2R4 and PLCß2 levels, and increased podocyte cell viability as well as protein expressions of ZO-1 and nephrin, biomarkers of podocyte slit diaphragm, in high glucose-cultured MPC cells. However, blockage of mTAS2R4 signaling with mTAS2R4 blockers γ-aminobutyric acid and abscisic acid, a Gßγ inhibitor Gallein, or a PLCß2 inhibitor U73122 all abolished the effects of quinine on NLRP3 inflammasome and p-NF-κB p65 as well as the functional podocyte proteins in MPC cells in a high glucose condition. Furthermore, knockdown of mTAS2R4 with lentivirus-carrying Tas2r108 shRNA also ablated the effect of quinine on the key molecules of the above inflammatory signalings and podocyte functions in high glucose-cultured MPC cells. In summary, we demonstrated that activation of TAS2R4 signaling alleviated the podocyte injury caused by chronic high glucose, and inhibition of NF-κB p65 and NLRP3 inflammasome mediated the protective effects of TAS2R4 activation on podocytes. Moreover, activation of TAS2R4 signaling could be an important strategy for prevention and treatment of diabetic kidney disease.

Effects of Great Gerbil Disturbance on Photosynthetic Characteristics and Nutrient Status of Haloxylon ammodendron.

Rodents, such as those that feed on plants and nest in plant roots, can significantly affect the growth and development of desert plants. The aim of this study was to investigate the effects of Rhombomys opimus disturbance on the photosynthetic characteristics and nutrient status of Haloxylon ammodendron at different growth stages in the Gurbantunggut Desert. The effects of great gerbil disturbance on the photosynthetic characteristics of H. ammodendron at different growth stages were investigated by measuring the gas exchange parameters, instantaneous water use efficiency, and chlorophyll fluorescence parameters of H. ammodendron at different ages (young, middle, and adult) under the disturbance of great gerbils. The soil nutrients in the assimilated branches and rhizosphere of H. ammodendron at different growth stages were tracked to reveal the relationship between the H. ammodendron nutrient content and gerbil disturbance. The results showed that great gerbil disturbance decreased the organic carbon content in the rhizosphere soil of adult H. ammodendron and increased the total nitrogen content in the rhizosphere soil and the nitrogen and potassium contents in the assimilated branches at each growth stage. The net photosynthetic rate and instantaneous water use efficiency of H. ammodendron decreased at each growth stage, and the maximum photochemical efficiency and non-photochemical quenching parameters of the young H. ammodendron decreased. However, the actual photochemical efficiency and photochemical parameters of the middle H. ammodendron increased. It was concluded that the disturbance of great gerbils decreased the photosynthetic capacity of H. ammodendron and increased the content of total nitrogen in the soil and nitrogen and potassium in the plant. This study revealed that the Gurbantunggut Desert great gerbil and H. ammodendron do not have a simple predation relationship. It laid a foundation for the study of the moderate disturbance threshold and better use of the mutually beneficial relationship between the two.

Formation of lipid-derived volatile products through lipoxygenase (LOX)- and hydroperoxide lyase (HPL)- mediated pathway in oat, barley and soy bean.

The aim of this study was to explore the formation of volatile lipid oxidation products by the lipoxygenase (LOX)-hydroperoxide lyase (HPL)-mediated pathway in oat, barley and soy bean. LOX activity was found only in barley and soy bean samples, but the lipase and HPL activity was detected in all samples. HPL showed particularly high activity with 13-hydroperoxides, while the activity was quite low when using 9-hydroperoxides, especially in the oat and barley. The optimum pH for HPL in different samples was similar, i.e., pH 6-7. In this condition, the volatile compounds formed dramatically with aldehydes and furans as the dominant products. Furthermore, a remarkable enzymatic degradation of lipids occurred during the preparation of food models with highly refined rapeseed oil (RO) and rapeseed oil fatty acid (ROFA) emulsions, where the ROFAs were more prone to oxidation than RO. This study shows the significance of lipid-degrading enzymes in plant-food flavour formation.

Pathogenic fungi synergistically cooperate with Serratia marcescens to increase cockroach mortality.

The abuse of chemical insecticides has led to strong resistance in cockroaches, and biopesticides with active ingredients based on insect pathogens have good development prospects; however, their slow effect has limited their practical application, and improving their effectiveness has become an urgent problem. In this study, the interaction between Serratia marcescens and Metarhizium anisopliae enhanced their virulence against Blattella germanica and exhibited a synergistic effect. The combination of S. marcescens and M. anisopliae caused more severe tissue damage and accelerated the proliferation of the insect pathogen. The results of high-throughput sequencing demonstrated that the gut microbiota was dysbiotic, the abundance of the opportunistic pathogen Weissella cibaria increased, and entry into the hemocoel accelerated the death of the German cockroaches. In addition, the combination of these two agents strongly downregulated the expression of Imd and Akirin in the IMD pathway and ultimately inhibited the expression of antimicrobial peptides (AMPs). S. marcescens released prodigiosin to disrupted the gut homeostasis and structure, M. anisopliae released destruxin to damaged crucial organs, opportunistic pathogen Weissella cibaria overproliferated, broke the gut epithelium and entered the hemocoel, leading to the death of pests. These findings will allow us to optimize the use of insect pathogens for the management of pests and produce more effective biopesticides.

Visualization of Individual RNA Molecules by Proximity Ligation-Based Chromogenic In Situ Hybridization Assay.

RNA in situ hybridization reveals the abundance and location of gene expression in cells or tissues, providing a technical basis for the clinical diagnosis of diseases. In this chapter, we show a "V" shape probe-mediated single-molecule chromogenic in situ hybridization (vsmCISH) technique for bright-field visualization of individual RNA molecules. In our method, several pairs of target hybridization probes are hybridized to RNA molecules and each probe pair forms a "V" shape overhang. The overhang oligonucleotides then mediated the proximity ligation to form DNA circles, followed by rolling circle amplification for signal enhancement and enzyme-catalyzed chromogenic reaction-based readout. The colorimetric assay avoids problems such as photobleaching and autofluorescence of current fluorescent in situ hybridization-based single-molecule RNA detection techniques. Furthermore, the relatively straightforward protocol makes the method useful for biological research and clinical diagnosis applications.

Zinc Oxide Nanoparticles Alleviate Salt Stress in Cotton (Gossypium hirsutum L.) by Adjusting Na+/K+ Ratio and Antioxidative Ability.

Soil salinization poses a threat to the sustainability of agricultural production and has become a global issue. Cotton is an important cash crop and plays an important role in economic development. Salt stress has been harming the yield and quality of many crops, including cotton, for many years. In recent years, soil salinization has been increasing. It is crucial to study the mechanism of cotton salt tolerance and explore diversified materials and methods to alleviate the salt stress of cotton for the development of the cotton industry. Nanoparticles (NPs) are an effective means to alleviate salt stress. In this study, zinc oxide NPs (ZnO NPs) were sprayed on cotton leaves with the aim of investigating the intrinsic mechanism of NPs to alleviate salt stress in cotton. The results show that the foliar spraying of ZnO NPs significantly alleviated the negative effects of salt stress on hydroponic cotton seedlings, including the improvement of above-ground and root dry and fresh weight, leaf area, seedling height, and stem diameter. In addition, ZnO NPs can significantly improve the salt-induced oxidative stress by reducing the levels of MDA, H2O2, and O2- and increasing the activities of major antioxidant enzymes, such as superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT). Furthermore, RNA-seq showed that the foliar spraying of ZnO NPs could induce the expressions of CNGC, NHX2, AHA3, HAK17, and other genes, and reduce the expression of SKOR, combined with the CBL-CIPK pathway, which alleviated the toxic effect of excessive Na+ and reduced the loss of excessive K+ so that the Na+/K+ ratio was stabilized. In summary, our results indicate that the foliar application of ZnO NPs can alleviate high salt stress in cotton by adjusting the Na+/K+ ratio and regulating antioxidative ability. This provides a new strategy for alleviating the salt stress of cotton and other crops, which is conducive to the development of agriculture.

The combination of breast cancer PDO and mini-PDX platform for drug screening and individualized treatment.

The majority of advanced breast cancers exhibit strong aggressiveness, heterogeneity, and drug resistance, and currently, the lack of effective treatment strategies is one of the main challenges that cancer research must face. Therefore, developing a feasible preclinical model to explore tailored treatments for refractory breast cancer is urgently needed. We established organoid biobanks from 17 patients with breast cancer and characterized them by immunohistochemistry (IHC) and next generation sequencing (NGS). In addition, we in the first combination of patient-derived organoids (PDOs) with mini-patient-derived xenografts (Mini-PDXs) for the rapid and precise screening of drug sensitivity. We confirmed that breast cancer organoids are a high-fidelity three-dimension (3D) model in vitro that recapitulates the original tumour's histological and genetic features. In addition, for a heavily pretreated patient with advanced drug-resistant breast cancer, we combined PDO and Mini-PDX models to identify potentially effective combinations of therapeutic agents for this patient who were alpelisib + fulvestrant. In the drug sensitivity experiment of organoids, we observed changes in the PI3K/AKT/mTOR signalling axis and oestrogen receptor (ER) protein expression levels, which further verified the reliability of the screening results. Our study demonstrates that the PDO combined with mini-PDX model offers a rapid and precise drug screening platform that holds promise for personalized medicine, improving patient outcomes and addressing the urgent need for effective therapies in advanced breast cancer.

The Brassinosteroid Receptor StBRI1 Promotes Tuber Development by Enhancing Plasma Membrane H+-ATPase Activity in Potato.

The brassinosteroid (BR) receptor BRASSINOSTEROID-INSENSITIVE 1 (BRI1) plays a critical role in plant growth and development. Although much is known about how BR signaling regulates growth and development in many crop species, the role of StBRI1 in regulating potato (Solanum tuberosum) tuber development is not well understood. To address this question, a series of comprehensive genetic and biochemical methods were applied in this investigation. It was determined that StBRI1 and Solanum tuberosum PLASMA MEMBRANE (PM) PROTON ATPASE2 (PHA2), a PM-localized proton ATPase, play important roles in potato tuber development. The individual overexpression of StBRI1 and PHA2 led to a 22% and 25% increase in tuber yield per plant, respectively. Consistent with the genetic evidence, in vivo interaction analysis using double transgenic lines and PM H+-ATPase activity assays indicated that StBRI1 interacts with the C-terminus of PHA2, which restrains the intramolecular interaction of the PHA2 C-terminus with the PHA2 central loop to attenuate autoinhibition of PM H+-ATPase activity, resulting in increased PHA2 activity. Furthermore, the extent of PM H+-ATPase autoinhibition involving phosphorylation-dependent mechanisms corresponds to phosphorylation of the penultimate Thr residue (Thr-951) in PHA2. These results suggest that StBRI1 phosphorylates PHA2 and enhances its activity, which subsequently promotes tuber development. Altogether, our results uncover a BR-StBRI1-PHA2 module that regulates tuber development and suggest a prospective strategy for improving tuberous crop growth and increasing yield via the cell surface-based BR signaling pathway.

Metal-Halogen Interactions Inducing Phase Separation for Self-Healing and Tough Ionogels with Tunable Thermoelectric Performance.

Ionic liquid-based thermoelectric gels become a compelling candidate for thermoelectric power generation and sensing due to their giant thermopower, good thermal stability, high flexibility, and low-cost production. However, the materials reported to date suffer from canonical trade-offs between self-healing ability, stretchability, strength, and ionic conductivity. Herein, a self-healing and tough ionogel (PEO/LiTFSI/EmimCl) with tunable thermoelectric properties by tailoring metal-halogen bonding interactions, is developed. Different affinities between polymer matrix and salts are exploited to induce phase separation, resulting in simultaneous enhancement of ionic conductivity and mechanical strength. Molecular dynamics (MD) simulations and spectroscopic analyses show that Cl- ions impair the lithium-ether oxygen coordination, leading to changes in chain conformation. The migration difference between cations and anions is thus widened and a transition from n-type to p-type thermoelectric ionogels is realized. Furthermore, the dynamic interactions of metal-ligand coordination and hydrogen bonding yield autonomously self-healing capability, large stretchability (2000%), and environment-friendly recyclability. Benefiting from these fascinating properties, the multifunctional PEO-based ionogels are applied in sensors, supercapacitors, and thermoelectric power generation modules. The strategy of tuning solvation dominance to address the trade-offs in thermoelectric ionogels and optimize their macroscopic properties offers new possibilities for the design of advanced ionogels.

Tracing fossil-based plastics, chemicals and fertilizers production in China.

Phasing down fossil fuels is crucial for climate mitigation. Even though 80-90% of fossil fuels are used to provide energy, their use as feedstock to produce plastics, fertilizers, and chemicals, is associated with substantial CO2 emissions. However, our understanding of hard-to-abate chemical production remains limited. Here we developed a chemical process-based material flow model to investigate the non-energy use of fossil fuels and CO2 emissions in China. Results show in 2017, the chemical industry used 0.18 Gt of coal, 88.8 Mt of crude oil, and 12.9 Mt of natural gas as feedstock, constituting 5%, 15%, and 7% of China's respective total use. Coal-fed production of methanol, ammonia, and PVCs contributes to 0.27 Gt CO2 emissions ( ~ 3% of China's emissions). As China seeks to balance high CO2 emissions of coal-fed production with import dependence on oil and gas, improving energy efficiency and coupling green hydrogen emerges as attractive alternatives for decarbonization.

CD44v5 domain regulates crosstalk between TNBC cells and tumor-associated macrophages by enhancing the IL-4R/STAT3 axis.

Triple-negative breast cancer (TNBC) has greater infiltration of M2-like macrophages (TAMs), which enhances cancer cell invasion and leads to a poor prognosis. TNBC progression is mediated by both tumor cells and the tumor microenvironment (TME). Here we elucidate the mechanism of the interaction between TNBC cells and TAMs. In this study, we confirmed that CD44v5 is highly expressed in TNBC, which drives TNBC cell metastasis and promotes TAM polarization by co-localizing with IL4Rα and inhibiting its internalization and degradation, thereby promoting activation of the STAT3/IL6 signaling axis. At the same time, TAMs also facilitate TNBC cell metastasis by secreting IL-4, IL-6, and other cytokines, in which the IL-4/IL-4R/STAT3/IL-6 signaling axis plays the same role for TNBC cells responding to TAMs. Moreover, we found that the above progress could be suppressed when the CD44v5 domain was blocked. We demonstrated that the CD44v5/IL-4R/STAT3/IL-6 signaling pathway plays a key role in TNBC cell metastasis, and in TNBC cells inducing TAM polarization and responding to TAMs, promoting metastasis. Collectively, we suggest that the CD44v5 domain may be a promising target for regulating the TME of TNBC as well as treating TNBC.

Intramolecular Quaternary Carbon Nitride Homojunction for Enhanced Visible Light Hydrogen Production.

In this work, an intramolecular carbon nitride (CN)-based quaternary homojunction functionalized with pyridine rings is prepared via an in situ alkali-assisted copolymerization strategy of bulk CN and 2-aminopyridine for efficient visible light hydrogen generation. In the obtained structure, triazine-based CN (TCN), heptazine-based CN (HCN), pyridine unit incorporated TCN, and pyridine ring inserted HCN constitute a special multicomponent system and form a built-in electric field between the crystalline semiconductors by the arrangement of energy band levels. The electron-withdrawing function of the conjugated heterocycle can trigger the skeleton delocalization and edge induction effect. Highly accelerated photoelectron-hole transfer rates via multi-stepwise charge migration pathways are achieved by the synergistic effect of the functional group modification and molecular quaternary homojunction. Under the addition of 5 mg 2-aminopyridine, the resulting homojunction framework exhibits a significantly improved hydrogen evolution rate of 6.64 mmol g-1 h-1 with an apparent quantum efficiency of 12.27% at 420 nm. Further, the catalyst verifies its potential commercial value since it can produce hydrogen from various real water environments. This study provides a reliable way for the rational design and fabrication of intramolecular multi-homojunction to obtain high-efficient photocatalytic reactions.