IDD10-NAC079 transcription factor complex regulates sheath blight resistance by inhibiting ethylene signaling in rice.

INTRODUCTION: Rhizoctonia solani Kühn is a pathogen causing rice sheath blight (ShB). Ammonium transporter 1 (AMT1) promotes resistance of rice to ShB by activating ethylene signaling. However, how AMT1 activates ethylene signaling remains unclear. OBJECTIVE: In this study, the indeterminate domain 10 (IDD10)-NAC079 interaction model was used to investigate whether ethylene signaling is modulated downstream of ammonium signaling and modulates ammonium-mediated ShB resistance. METHODS: RT-qPCR assay was used to identify the relative expression levels of nitrogen and ethylene related genes. Yeast two-hybrid assays, Bimolecular fluorescence complementation (BiFC) and Co-immunoprecipitation (Co-IP) assay were conducted to verify the IDD10-NAC079-calcineurin B-like interacting protein kinase 31 (CIPK31) transcriptional complex. Yeast one-hybrid assay, Chromatin immunoprecipitation (ChIP) assay, and Electrophoretic mobility shift assay (EMSA) were used to verify whether ETR2 was activated by IDD10 and NAC079. Ethylene quantification assay was used to verify ethylene content in IDD10 transgenic plants. Genetic analysis is used to detect the response of IDD10, NAC079 and CIPK31 to ShB infestation. RESULTS: IDD10-NAC079 forms a transcription complex that activates ETR2 to inhibit the ethylene signaling pathway to negatively regulating ShB resistance. CIPK31 interacts and phosphorylates NAC079 to enhance its transcriptional activation activity. In addition, AMT1-mediated ammonium absorption and subsequent N assimilation inhibit the expression of IDD10 and CIPK31 to activate the ethylene signaling pathway, which positively regulates ShB resistance. CONCLUSION: The study identified the link between ammonium and ethylene signaling and improved the understanding of the rice resistance mechanism.

Prevalence and Residual Risk of HIV in Volunteer Blood Donors of Zhejiang Province, China, from 2018 to 2022.

Background: Blood safety levels have been significantly improved since the implementation of nucleic acid amplification technology (NAT) testing for blood donors. However, there remains a residual risk of transfusion transmission infections. This study aimed to evaluate the prevalence of HIV and its residual risk transmission among volunteer blood donors of Zhejiang Province, China, for five years after NAT implementation. Materials and Methods: All specimens and information were collected from voluntary unpaid donors at all blood services in Zhejiang Province, China, from January 2018 to December 2022. The HIV antibody or antigen and HIV RNA were detected using enzyme-linked immunosorbent assay and NAT, respectively. The HIV residual risk transmission was calculated using the incidence or window period model. Results: A total of 3,375,678 voluntary blood donors were detected, revealing an HIV prevalence of 9.92/100000. The HIV prevalence of blood donors in 12 blood services in Zhejiang Province was 6.11, 6.98, 7.45, 8.21, 8.36, 8.94, 9.04, 9.66, 9.73, 10.22, 11.80, and 12.47 per 100000 donors, without statistically significant difference observed among the services (p > 0.05). The HIV prevalence of males (15.49/100000) was significantly higher compared to females (1.95/100000; p < 0.05). There was an insignificant difference in HIV prevalence among blood donors of all different age groups (p > 0.05), but the HIV prevalence in the 26-35 age group and 18-25 age group was significantly higher compared to the 36-45 age group (p < 0.05). The difference in HIV prevalence between first-time blood donors (13.65/100,000) and repeat blood donors (6.78/100,000) was statistically significant (p < 0.05). From 2018 to 2022, the HIV residual risk in blood transfusion transmission was 0.266/100000. Conclusion: The prevalence of HIV among blood donors in Zhejiang Province, China, is associated with age, gender, and times of blood donation. The HIV residual risk in blood transfusion transmission remains low in the province, and increasing the rate of repeat blood donors is beneficial to improve blood safety.

QL1604 combined with bevacizumab as an innovative first-line treatment for HCC patient with extensive metastasis who showed remarkable effect: a case report.

Hepatocellular carcinoma (HCC) is a common and highly malignant tumor with poor outcomes, especially when it metastasizes. In this report, we present the case of a 64-year-old male patient diagnosed with recurrence and multiple metastases of HCC 7 years after surgery. As the tumor invaded the spinal canal and pressed on the spinal cord, the patient experienced paralysis in the lower limbs. After undergoing surgical resection for spinal decompression, the patient chose an innovative regimen: QL1604 200 mg every 3 weeks plus bevacizumab 675 mg every 3 weeks as first-line treatment. From July 2022 to February 2024, the patient has regularly received the treatment. During the treatment, the paralysis symptoms of the patient gradually improved, and the motor function of the lower limbs completely returned to normal. When re-evaluated his spinal cord injury, the Frankel grade of the patient was downgraded from C to E. The tumor shrank to reach a state of PR and lasted for one and a half years. QL1604 combined with bevacizumab demonstrated excellent efficacy and minimal side effects in this patient. This new combined therapy holds potential as a first-line treatment strategy.

Highly reversible transition metal migration in superstructure-free Li-rich oxide boosting voltage stability and redox symmetry.

The further practical applications of Li-rich layered oxides are impeded by voltage decay and redox asymmetry, which are closely related to the structural degradation involving irreversible transition metal migration. It has been demonstrated that the superstructure ordering in O2-type materials can effectively suppress voltage decay and redox asymmetry. Herein, we elucidate that the absence of this superstructure ordering arrangement in a Ru-based O2-type oxide can still facilitate the highly reversible transition metal migration. We certify that Ru in superstructure-free O2-type structure can unlock a quite different migration path from Mn in mostly studied cases. The highly reversible migration of Ru helps the cathode maintain the structural robustness, thus realizing terrific capacity retention with neglectable voltage decay and inhibited oxygen redox asymmetry. We untie the knot that the absence of superstructure ordering fails to enable a high-performance Li-rich layered oxide cathode material with suppressed voltage decay and redox asymmetry.

Clinical significance of downregulated NISCH expression in skin cutaneous melanoma: Modulation of tumor cell invasion, migration, and EMT via PAK1 inhibition.

OBJECTIVE: This study aimed to investigate the expression and functional role of NISCH in skin cutaneous melanoma (SKCM), exploring its association with clinical characteristics and its potential impact on human skin melanoma cell behavior. METHODS: The research assessed differential NISCH expression in SKCM tissues using the GEPIA (Gene Expression Profiling Interactive Analysis) database and validated these findings through immunohistochemical staining of 45 clinical samples. To affirm NISCH expression at the cellular level, three human skin melanoma cell lines (RPMI-7951, A375, MEL-5), and the human normal skin cell line HEMa underwent quantitative reverse transcription-polymerase chain reaction (qRT-PCR) and Western blotting. Transwell experiments evaluated the migration and invasion capabilities of RPMI-7951 and A375 cells post-transduction with NISCH or PAK1 lentiviral activation particles. Additionally, qRT-PCR analysis of epithelial-mesenchymal transition (EMT)-related gene expression (Vimentin, E-cadherin, N-cadherin) was conducted in A375 and RPMI-7951 cells. RESULTS: SKCM tissues exhibited significantly reduced NISCH expression compared to normal tissues. Immunohistochemical analysis revealed predominant nuclear localization of NISCH in melanoma cells, with reduced expression significantly correlating with sex, advanced stage, and lymph node metastasis. Melanoma cell lines displayed lower NISCH expression levels compared to normal skin cells. Functional experiments showcased that NISCH overexpression suppressed p-PAK1/PAK1, while PAK1 upregulation notably increased melanoma cell migration, invasion, and induced EMT. Remarkably, NISCH overexpression counteracted PAK1-induced effects on EMT, migration, and invasion in melanoma cells. CONCLUSION: NISCH may significantly influence the aggressive behavior of SKCM cells via the PAK1 pathway, making it a potential therapeutic target for managing melanoma metastasis.

Genetic distribution, characterization, and function of Escherichia coli type III secretion system 2 (ETT2).

Many Gram-negative bacteria use type Ⅲ secretion system (T3SS) to inject effector proteins and subvert host signaling pathways, facilitating the growth, survival, and virulence. Notably, some bacteria harbor multiple distinct T3SSs with different functions. An extraordinary T3SS, the Escherichia coli Type III Secretion System 2 (ETT2), is widespread among Escherichia coli (E. coli) strains. Since many ETT2 carry genetic mutations or deletions, it is thought to be nonfunctional. However, increasing studies highlight ETT2 contributes to E. coli pathogenesis. Here, we present a comprehensive overview of genetic distribution and characterization of ETT2. Subsequently, we outline its functional potential, contending that an intact ETT2 may retain the capacity to translocate effector proteins and manipulate the host's innate immune response. Given the potential zoonotic implications associated with ETT2-carrying bacteria, further investigations into the structure, function and regulation of ETT2 are imperative for comprehensive understanding of E. coli pathogenicity and the development of effective control strategies.

Neuroimaging features of cognitive impairments in schizophrenia and major depressive disorder.

Cognitive dysfunctions are one of the key symptoms of schizophrenia (SZ) and major depressive disorder (MDD), which exist not only during the onset of diseases but also before the onset, even after the remission of psychiatric symptoms. With the development of neuroimaging techniques, these non-invasive approaches provide valuable insights into the underlying pathogenesis of psychiatric disorders and information of cognitive remediation interventions. This review synthesizes existing neuroimaging studies to examine domains of cognitive impairment, particularly processing speed, memory, attention, and executive function in SZ and MDD patients. First, white matter (WM) abnormalities are observed in processing speed deficits in both SZ and MDD, with distinct neuroimaging findings highlighting WM connectivity abnormalities in SZ and WM hyperintensity caused by small vessel disease in MDD. Additionally, the abnormal functions of prefrontal cortex and medial temporal lobe are found in both SZ and MDD patients during various memory tasks, while aberrant amygdala activity potentially contributes to a preference to negative memories in MDD. Furthermore, impaired large-scale networks including frontoparietal network, dorsal attention network, and ventral attention network are related to attention deficits, both in SZ and MDD patients. Finally, abnormal activity and volume of the dorsolateral prefrontal cortex (DLPFC) and abnormal functional connections between the DLPFC and the cerebellum are associated with executive dysfunction in both SZ and MDD. Despite these insights, longitudinal neuroimaging studies are lacking, impeding a comprehensive understanding of cognitive changes and the development of early intervention strategies for SZ and MDD. Addressing this gap is critical for advancing our knowledge and improving patient prognosis.

A DIRIGENT Gene GmDIR26 Regulates Pod Dehiscence in Soybean.

Pod dehiscence brings much loss for modern agricultural production, and multiple pod dehiscence components have been identified in many plant species. However, the pod dehiscence regulation factors in soybean are limited. In this study, we investigate the function of GmDIR26, a close homologues gene of pod dehiscence genes GmPdh1, PvPdh1, and CaPdh1, in the regulation of pod dehiscence in soybean. The secondary and tertiary structure analysis reveals that GmDIR26 protein has a similar structure with GmPdh1, PvPdh1, and CaPdh1 proteins. Synteny analysis of soybean and chickpea genomes shows that the genomic region surrounding GmDIR26 and CaPdh1 might be evolved from the same ancestor, and these two genes might have similar function. GmDIR26 shows an increased expression pattern during pod development and reaches a peak at beginning seed stage. Meanwhile, GmDIR26 exhibits high expression levels in dorsal suture and pod wall, but low expression pattern in ventral suture. In addition, GmDIR26 shows higher expression levels in pod dehiscence genotype than that in pod indehiscence accessions. Overexpression of GmDIR26 in soybean increases pod dehiscence in transgenic plants, of which the lignin layer in inner sclerenchyma pods is thicker and looser. The expression levels of several pod dehiscence genes are altered. Our study provides important information for further modification of pod dehiscence resistance soybean and characterization of soybean pod dehiscence regulation network.

Design, synthesis, and bioactivity evaluation of clindamycin derivatives against multidrug-resistant bacterial strains.

Our research aims to reduce the bacterial resistance of clindamycin against Gram-positive bacteria and expand its range of bacterial susceptibility. First, we optimized the structure of clindamycin based on its structure-activity relationship. Second, we employed the fractional inhibitory concentration method to detect drugs suitable for combination with clindamycin derivatives. We then used a linker to connect the clindamycin derivatives with the identified combined therapy drugs. Finally, we tested antibacterial susceptibility testing and conducted in vitro bacterial inhibition activity assays to determine the compounds. with the highest efficacy. The results of our study show that we synthesized clindamycin propionate derivatives and clindamycin homo/heterodimer derivatives, which exhibited superior antibacterial activity compared to clindamycin and other antibiotics against both bacteria and fungi. In vitro bacteriostatic activity testing against four types of Gram-negative bacteria and one type of fungi revealed that all synthesized compounds had bacteriostatic effects at least 1000 times better than clindamycin and sulfonamides. The minimum inhibitory concentration (MIC) values for these compounds ranged from 0.25 to 0.0325 mM. Significantly, compound 5a demonstrated the most potent inhibitory activity against three distinct bacterial strains, displaying MIC values spanning from 0.0625 to 0.0325 mM. Furthermore, our calculations indicate that compound 5a is safe for cellular use. In conclusion, the synthesized compounds hold great promise in addressing bacterial antibiotic resistance.

Revolutionizing Diabetic Foot Ulcer Care: The Senotherapeutic Approach.

Diabetic foot ulcers (DFUs) are a prevalent and profoundly debilitating complication that afflicts individuals with diabetes mellitus (DM). These ulcers are associated with substantial morbidity, recurrence rates, disability, and mortality, imposing substantial economic, psychological, and medical burdens. Timely detection and intervention can mitigate the morbidity and disparities linked to DFU. Nevertheless, current therapeutic approaches for DFU continue to grapple with multifaceted limitations. A growing body of evidence emphasizes the crucial role of cellular senescence in the pathogenesis of chronic wounds. Interventions that try to delay cellular senescence, eliminate senescent cells (SnCs), or suppress the senescence-associated secretory phenotype (SASP) have shown promise for helping chronic wounds to heal. In this context, targeting cellular senescence emerges as a novel therapeutic strategy for DFU. In this comprehensive review, we look at the pathology and treatment of DFU in a systematic way. We also explain the growing importance of investigating SnCs in DFU and highlight the great potential of senotherapeutics that target SnCs in DFU treatment. The development of efficacious and safe senotherapeutics represents a pioneering therapeutic approach aimed at enhancing the quality of life for individuals affected by DFU.

Prediction analysis of carbon emission in China's electricity industry based on the dual carbon background.

The electric power sector is the primary contributor to carbon emissions in China. Considering the context of dual carbon goals, this paper examines carbon emissions within China's electricity sector. The research utilizes the LMDI approach for methodological rigor. The results show that the cumulative contribution of economies scale, power consumption factors and energy structure are 114.91%, 85.17% and 0.94%, which contribute to the increase of carbon emissions, the cumulative contribution of power generation efficiency and ratio of power dissipation to generation factor are -19.15% and -0.01%, which promotes the carbon reduction. The decomposition analysis highlights the significant influence of economic scale on carbon emissions in the electricity industry, among the seven factors investigated. Meanwhile, STIRPAT model, Logistic model and GM(1,1) model are used to predict carbon emissions, the average relative error between actual carbon emissions and the predicted values are 0.23%, 8.72% and 7.05%, which indicates that STIRPAT model is more suitable for medium- to long-term predictions. Based on these findings, the paper proposes practical suggestions to reduce carbon emissions and achieve the dual carbon goals of the power industry.

Causality of Helicobacter pylori infection on eosinophilic esophagitis and potential pathogenesis: a Mendelian randomization study.

Background: Observational studies have indicated a possible connection between Helicobacter pylori (H. pylori) infection and eosinophilic esophagitis (EoE), but their causal relationship has yet to be established. To investigate the causal associations between H. pylori infection and EoE, we performed a Mendelian randomization (MR) analysis. Methods: Firstly, we conducted both univariable and multivariable Mendelian randomization (MR) analyses. Furthermore, a two-step MR was carried out to ascertain the potential underlying pathways of these associations, particularly the involvement of inflammatory cytokines. We employed the inverse-variance weighted (IVW) method as the main analysis in our MR study. To enhance the credibility of the results, we also conducted several sensitivity analyses. Results: Our study demonstrated a noteworthy correlation between genetically predicted anti-H. pylori IgG antibody levels and a reduced risk of EoE (OR=0.325, 95% CI=0.165-0.643, P value=0.004, adj p value=0.009). No significant causal associations were detected between other H. pylori antibodies and EoE in our study. When it comes to multivariable MR analysis controlling for education attainment, household income, and deprivation individually, the independent causal impact of anti-H. pylori IgG on EoE persisted. Surprisingly, the two-step MR analysis indicated that inflammatory factors (IL-4, IL-5, IL-13, IL-17, and IFN-γ) did not appear to mediate the protective effect of H. pylori infection against EoE. Conclusion: Findings suggested that among the range of H. pylori-related antibodies, anti-H. pylori IgG antibody is the sole causal factor associated with protection against EoE. Certain inflammatory factors may not be involved in mediating this association. These findings make a significant contribution to advancing our understanding of the pathogenesis of EoE and its evolving etiology.

Peritendinous Submembrane Access Technique for Management of Acute Ruptures of the Achilles Tendon: A Retrospective Study of 249 Cases.

OBJECTIVE: Percutaneous repair is an alternative to open surgical repair of the Achilles tendon with comparable, functional results and low re-rupture and infection rates; however, sural nerve injury is a known complication. The purpose of this study is to design a new surgical procedure, the minimally invasive peritendinous submembrane access technique (MIS-PSAT). It offers optimal results, with excellent functional outcomes, and with minimal soft tissue complications and sural nerve injury. METHODS: This retrospective study included 249 patients with acute closed Achilles tendon ruptures treated at our institution between 2009 and 2019. All patients underwent MIS-PSAT at our institution and were followed up for 8-48 months. Functional evaluation was based on the Achilles tendon total rupture score (ATRS) and the American Orthopedic Foot and Ankle Society Ankle-Hindfoot Scale (AOFAS-AHS), associated with local complications and isokinetic tests. RESULTS: None of the patients had infection, necrosis, or sural nerve injury. Re-rupture occurred in two cases. The average times to return to work and sports was 10.4 and 31.6 weeks, respectively. The average ATRS and AOFAS-AHS scores were 90.2 and 95.7, respectively, with an excellent rate of 99.5%. Isokinetic tests showed that ankle function on the affected side was comparable with that on the healthy side (p > 0.05). CONCLUSION: The MIS-PSAT for acute Achilles tendon rupture is easy to perform with few complications. Importantly, the surgical technique reduces the risk of sural nerve injuries. Patients have high postoperative satisfaction, low re-rupture rates, and muscle strength, and endurance can be restored to levels similar to those on the healthy side.

Mother-reliant or Self-reliant: The germination strategy of seeds in a species-rich alpine meadow is associated with the existence of pericarps.

BACKGROUND AND AIMS: Some plants germinate their seeds enclosed by a pericarp, while others lack the outer packaging. As a maternal tissue, may impart seeds with different germination strategies. Plants in a community with different flowering times may separately disperse and germinate their seeds; therefore, flowering time can be considered as one manifestation of maternal effects on offspring. The mass of the seed is another important factor influencing germination and represents the intrinsic resource of seed that supports the germination. Using seeds from a species-rich alpine meadow located in the Hengduan Mountains of China, a global biodiversity hotspot, we aim to illustrate whether and how the type of seed (with and without a pericarp) modulates the interaction of flowering time and seed mass with germination. METHODS: Seeds were germinated under a generally favorable condition and germination speed (estimated by mean germination time, MGT) was calculated. We quantified the maternal conditions by separation of flowering time for 67 species in the meadow, in which 31 produced seeds with pericarps and 36 yielded seeds without pericarps, respectively. We also weighed one hundred seeds to assess their mass. KEY RESULTS: The MGT varied between the two types of seed. For seeds with pericarps, MGT was associated with flowering time but not with seed mass. Plants with earlier flowering times in the meadow exhibited more rapid seed germination. For seeds without pericarp, the MGT depended on seed mass, with smaller seeds germinating more rapidly than larger seeds. CONCLUSIONS: The distinct responses of germination to flowering time and seed mass observed in seeds with and without pericarp suggest that germination strategies might be mother-reliant for seeds protected by pericarps but self-reliant for those without such protection. This novel finding improves our understanding of seed germination by integrating ecologically mediated maternal conditions and inherent genetic properties.

[Randomized,double-blind,parallel controlled,multicenter clinical trial of effectiveness and safety of Shexiang Zhuifeng Zhitong Ointment in alleviating pain in knee osteoarthritis(syndrome of cold-dampness obstruction)].

The Shexiang Zhuifeng Zhitong Ointment with the effects of dispelling wind, removing dampness, dissipating cold, and relieving pain is used for treating arthralgia, muscular pain, and sprain pain caused by cold-dampness obstruction. To evaluate the efficacy and safety of Shexiang Zhuifeng Zhitong Ointment in relieving the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction), a randomized, double-blind, parallel controlled, multicenter clinical trial was conducted. The stratified randomization method was used to randomize the 240 subjects into a treatment group and a control group in a ratio of 1∶1. In each group, 60 patients received external application for 12 h and the other 60 patients received external application for 6 h. The treatment group received external application of Shexiang Zhuifeng Zhitong Ointment, while the control group received external application of Shexiang Zhuifeng Ointment. The treatment lasted for 21 days in both groups. Follow-up was conducted on days 7, 14, and 21 of treatment. The results based on the full analysis set were as follows.(1)In visual analog scale(VAS) score, the mean difference in the VAS score between baseline and 12 h post-treatment was 3.02 in the treatment group and 2.31 in the control group, with a significant difference(P<0.05). The mean difference in the VAS score between baseline and 6 h post-treatment was 3.19 in the treatment group and 2.48 in the control group, with a significant difference(P<0.05).(2)Response rate in terms of VAS score, after treatment for 12 h, the response rate was 93.22% in the treatment group and 73.33% in the control group, with a significant difference(P<0.05). After treatment for 6 h, theresponse rate in the treatment group was 88.33%, which was higher than that(63.33%) in the control group(P<0.05).The results showed that Shexiang Zhuifeng Zhitong Ointment applied for 12 and 6 h effectively relieved the knee joint pain of patients with knee osteoarthritis due to cold-dampness obstruction, as demonstrated by the reduced VAS score, Western Ontario and McMaster Universities Arthritis Index(WOMAC), stiffness, and joint function score. Moreover, Shexiang Zhuifeng Zhitong Ointment outperformed the positive control Shexiang Zhuifeng Ointment in terms of reducing the VAS score, demonstrating a definitetherapeutic effect on the pain due to knee osteoarthritis(syndrome of cold-dampness obstruction).In addition, Shexiang Zhuifeng Zhitong Ointment did not cause other adverse reactions except for mild allergic reactions, which were common in the external application of traditional Chinese medicine plasters on the skin, inseveral patients.Neither other adverse reactions nor abnormalities of liver and kidney functions and electrocardiogram were observed. This ointment had high safety and could be popularized in clinical application.

MathEagle: Accurate prediction of drug-drug interaction events via multi-head attention and heterogeneous attribute graph learning.

BACKGROUND: Drug-drug interaction events influence the effectiveness of drug combinations and can lead to unexpected side effects or exacerbate underlying diseases, jeopardizing patient prognosis. Most existing methods are restricted to predicting whether two drugs interact or the type of drug-drug interactions, while very few studies endeavor to predict the specific risk levels of side effects of drug combinations. METHODS: In this study, we propose MathEagle, a novel approach to predict accurate risk levels of drug combinations based on multi-head attention and heterogeneous attribute graph learning. Initially, we model drugs and three distinct risk levels between drugs as a heterogeneous information graph. Subsequently, behavioral and chemical structure features of drugs are utilized by message passing neural networks and graph embedding algorithms, respectively. Ultimately, MathEagle employs heterogeneous graph convolution and multi-head attention mechanisms to learn efficient latent representations of drug nodes and estimates the risk levels of pairwise drugs in an end-to-end manner. RESULTS: To assess the effectiveness and robustness of the model, five-fold cross-validation, ablation experiments, and case studies were conducted. MathEagle achieved an accuracy of 85.85 % and an AUC of 0.9701 on the drug risk level prediction task and is superior to all comparative models. The MathEagle predictor is freely accessible at http://120.77.11.78/MathEagle/. CONCLUSIONS: The experimental results indicate that MathEagle can function as an effective tool for predicting accurate risk of drug combinations, aiding in guiding clinical medication, and enhancing patient outcomes.

The role of hydrogen-rich water in delaying the pulp breakdown of litchi fruit during postharvest storage.

Previous studies have indicated that hydrogen-rich water (HW) treatment can delay fruit ripening and senescence. However, little is known about the HW-delaying pulp breakdown. In this study, eight physiological characteristics revealed that HW treatment delayed both pericarp browning and pulp breakdown of litchi fruit. To gain a comprehensive understanding of the changes in litchi pulp, a combination of multiple metabolomics and gene expression analyses was conducted, assessing 67 primary metabolites, 103 volatiles, 31 amino acids, and 13 crucial metabolite-related genes. Results showed that HW treatment promoted starch degradation, decelerated cell wall degradation and glycolysis, and maintained the flavor and quality of litchi fruit. Furthermore, HW treatment stimulated the production of volatile alcohols, aldehydes, ketones, olefins, and amino acids, which might play a vital role in HW-delaying pulp breakdown. This study sheds light on the mechanism by which HW delayed pulp breakdown by investigating small molecule metabolites and metabolic pathways.