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Microbial communities play crucial roles in pollutant removal and system stability in biological systems for coking wastewater (CWW) treatment, but a comprehensive understanding of their structure and functions is still lacking. A five month survey of four sequential bioreactors, anoxic 1/oxic 1/anoxic 2/oxic 2 (A1/O1/A2/O2), was carried out in a full-scale CWW treatment system in China to elucidate operational performance and microbial ecology. The results showed that A1/O1/A2/O2 had excellent and stable performance for nitrogen removal. Both total nitrogen (TN; (17.38 ± 6.89) mg·L−1) and ammonium–nitrogen (NH4+-N; (2.10 ± 1.34) mg·L−1) in the final biological effluent satisfied the Chinese national standards for CWW. Integrated analysis of 16S ribosome RNA (rRNA) sequencing and metagenomic sequencing showed that the bacterial communities and metagenomic function profiles of A1 and O1 shared similar functional structures, while those of A2 significantly varied from those of other bioreactors (p

Intercropping has the potential to improve phosphorus (P) uptake and crop growth, but the potential benefits and relative contributions of root morphology and arbuscular mycorrhizal fungi (AMF) colonization are largely unknown for the intercropping of rice and soybean under dry cultivation. Both field and pot experiments were conducted with dry-cultivated rice (Oryza sativa L.) and soybean (Glycine max L. Merr.) grown alone or intercropped under two P levels. Two root separation modes between rice and soybean were employed to explore the contribution of AMF association and root plasticity on P uptake in intercrops. The results showed that rice/soybean intercropping resulted in a notable increase in the total biomass and yield compared to monoculture in the field. In the potted experiment, compared to the plastic root separation treatment (PS), the no root separation treatment (NS) increased the total biomass and P uptake by 9.4% and 19.9%, irrespective of the P levels. This was primarily attributable to a considerable enhancement in biomass and phosphorus uptake in soybean by 40.4% and 49.7%, which offset a slight decline in the rice of NS compared to PS by 26.8% and 18.0%, respectively. The results of random forest analysis indicate that the P uptake by the dominant species, soybean, was mainly contributed by root morphology, while rice was more dependent on AMF colonization in the intercropping system. Therefore, dry-cultivated rice/soybean intercropping enhances P uptake and productivity by leveraging complementary belowground strategies, with soybean benefiting primarily from root morphological adjustments and rice relying more on arbuscular mycorrhizal fungi colonization.

The aim of this study was to investigate the effects of organic fertilizer replacing part of the nitrogen fertilizers on the structure and diversity of the inter-root soil fungal communities of potatoes. By carrying out a field trial in Gaoquan Village, Tuanjie Town, Dingxi City, Gansu Province, the main potato-producing area in China, the optimal proportion of organic fertilizer to replace nitrogen fertilizer was determined to provide a scientific basis for the rational use of organic fertilizer to improve the structure and function of soil fungal communities. The experiment was laid out with six treatments: CK (no nitrogen fertilizer, phosphate and potash fertilizer applied), CF (nitrogen fertilizer alone, control), T1 (25% replacement of nitrogen fertilizer), T2 (50% replacement of nitrogen fertilizer), T3 (75% replacement of nitrogen fertilizer), and T4 (100% replacement of nitrogen fertilizer). A systematic study of the inter-root soil fungal community structure, diversity, and soil physicochemical properties during potato harvesting was conducted using high-throughput sequencing technology. The results show that the organic fertilizer replacing part of the nitrogen fertilizer significantly increased the content of alkaline dissolved nitrogen, quick-acting potassium, quick-acting phosphorus, and organic matter in the inter-root soil of the potatoes, and significantly reduced the pH value of the soil. There was a trend of decreasing soil fungal abundance and a significant decrease in the Alpha diversity of the soil fungi. The treatment groups in the soil had as their core fungi Acomycota, Mortierellomycota, Basidiomycota, and others. The organic fertilizers replacing the nitrogen fertilizers significantly altered the structural composition of the inter-root soil fungal community of the potatoes, and increased the differential fungi in the soil. The number of functionally diverse and complex fungi in the soil gradually increased, and the function of the fungal community gradually changed from Singularity to diversification and complexity. A redundancy analysis showed that the soil pH was the main environmental factor affecting the inter-root soil fungal communities of potatoes under organic fertilizer replacing N fertilizer.

In this article, we consider the following a class of Schrödinger-Poisson systems with $ p $-Laplacian in $ \mathbb{R}^{3} $ of the form: $ \begin{equation*} \left\{ \begin{array}{lll} -\Delta_{p}u+(\lambda b(x)+1)|u|^{p-2}u+\phi|u|^{s-2}u = g(u) &\mbox{in}\ \mathbb{R}^{3}, \\ -\Delta\phi = |u|^{s} &\mbox{in}\ \mathbb{R}^{3}, \end{array} \right. \end{equation*} $ where $ 1 < p < 3 $, $ \frac{p}{2} < s < p $, $ \Delta_{p}u : = div(|\nabla u|^{p-2}\nabla u) $ is the $ p $-Laplacian operator, $ \lambda $ is a positive parameter. Assume that the nonnegative function $ b $ possesses a potential well int$ (b^{-1}(\{0\})) $, which is composed of $ k $ disjoint components $ \Omega_{1}, \Omega_{2}, \cdots, \Omega_{k} $ and consider the nonlinearity $ g $ with subcritical growth. Using the variational methods and Morse iteration technique, the existence of positive multi-bump solutions are obtained.

OBJECTIVES This study examined the associations between adverse childhood experiences (ACEs) and diabetes within a social-ecological framework, incorporating personal and environmental unfavorable conditions during childhood from family, school, and community contexts. METHODS Data were obtained from the China Health and Retirement Longitudinal Study (2014 life history survey and 2015 survey), including 9,179 participants aged ≥45 years. ACEs were collected through self-report questionnaires, and participants were categorized based on the number of distinct ACEs experienced (0, 1, 2, 3, or ≥4 ACEs). Diabetes was defined by biomarkers, self-reported diagnosis, and treatment status. Logistic regression was conducted to explore the associations between ACEs and diabetes. Subgroup analyses were conducted by gender, age, and obesity status. RESULTS Compared with participants without ACEs, those exposed to any ACE (odds ratio [OR], 1.19; 95% confidence interval [CI], 1.01 to 1.40), 3 ACEs (OR, 1.32; 95% CI, 1.07 to 1.62) and ≥4 ACEs (OR, 1.29; 95% CI, 1.07 to 1.56) had an increased risk of diabetes. For each additional ACE, the risk of diabetes increased by about 5%. Regarding the source of ACEs, those originating from the family (OR, 1.23; 95% CI, 1.08 to 1.41) were associated with diabetes. In terms of specific ACE types, family members with substance abuse (OR, 1.23; 95% CI, 1.01 to 1.52), emotional abuse (OR, 1.28; 95% CI, 1.12 to 1.46), and poor parental relationship (OR, 1.25; 95% CI, 1.09 to 1.43) were associated with diabetes. CONCLUSIONS ACEs, particularly those originating from the family, were associated with diabetes. Interventions aimed at preventing and mitigating ACEs are essential for the early prevention of diabetes.

Heat stress during the reproductive stage results in major losses in yield and quality, which might be mainly caused by an energy imbalance. However, how energy status affected heat response, yield and quality remains unclear. No relationships were observed among the heat resistance, yield, and quality of the forty-nine early rice cultivars under normal temperature conditions. However, two cultivars, Zhuliangyou30 (ZLY30) and Luliangyou35 (LLY35), differing in heat resistance, yield, and quality were detected. The yield was higher and the chalkiness degree was lower in ZLY30 than in LLY35. Decreases in yields and increases in the chalkiness degree with temperatures were more pronounced in LLY35 than in ZLY30. The accumulation and allocation (ratio of the panicle to the whole plant) of dry matter weight and non-structural carbohydrates were higher in ZLY30 than in LLY35 across all sowing times and temperatures. The accumulation and allocation of dry matter weight and non-structural carbohydrates in panicles were higher in ZLY30 than in LLY35. Similar patterns were observed in the relative expression levels of sucrose unloading related genes SUT1 and SUT2 in grains. The ATP content was higher in the grains of LLY35 than in ZLY30, whereas the ATPase activity, which determined the energy status, was significantly lower in the former than in the latter. Thus, increased ATPase activity, which improved the energy status of rice, was the factor mediating the balance among heat-resistance, high-yield, and high-quality traits in rice.

IntroductionThe alterations of gut microbiota have been associated with multiple diseases. However, the relationship between gut microbiota and adverse outcomes of hyperlipidemic stroke patients remains unclear. Here we determined the gut microbial signature to predict the poor outcome of acute ischemic stroke (AIS) with hyperlipidemia (POAH).MethodsFecal samples from hyperlipidemic stroke patients were collected, which further analyzed by 16s rRNA gene sequencing. The diversity, community composition and differential gut microbiota were evaluated. The adverse outcomes were determined by modified Rankin Scale (mRS) scores at 3 months after admission. The diagnostic performance of microbial characteristics in predicting adverse outcomes was assessed by receiver operating characteristic (ROC) curves.ResultsOur results showed that the composition and structure of gut microbiota between POAH patients and good outcome of AIS with hyperlipidemia (GOAH) patients were different. The characteristic gut microbiota of POAH patients was that the relative abundance of Enterococcaceae and Enterococcus were increased, while the relative abundance of Lachnospiraceae, Faecalibacterium, Rothia and Butyricicoccus were decreased. Moreover, the characteristic gut microbiota were correlated with many clinical parameters, such as National Institutes of Health Stroke Scale (NIHSS) score, mean arterial pressure, and history of cerebrovascular disease. Moreover, the ROC models based on the characteristic microbiota or the combination of characteristic microbiota with independent risk factors could distinguish POAH patients and GOAH patients (area under curve is 0.694 and 0.971 respectively).ConclusionsThese findings revealed the microbial characteristics of POAH, which highlighted the predictive capability of characteristic microbiota in POAH patients.

The effective exploration and utilization of brackish water resources are crucial to alleviating the scarcity of freshwater in arid regions. This study focused on protected tomato plants and set up four irrigation salinity levels: T1 (2 g·L−1), T2 (4 g·L−1), T3 (6 g·L−1), and T4 (8 g·L−1), with freshwater irrigation as a control (CK). The aim was to investigate the effects of continuous brackish water irrigation on soil water-salt transport and tomato yield. The outcomes highlighted that the moisture content in different layers of soil exhibited a “high in the middle, low at both ends” pattern, with the primary accumulation of soil moisture occurring at the 40 cm depth. The range and moisture content of the soil wetted zone increased with elevated salinity levels. Under continuous brackish water irrigation, the range of the soil wetted zone expanded further for the autumn crops, and the moisture content significantly increased compared to the spring crops. The concentration of soil salt gradually decreased with increasing soil depth, exhibiting greater levels in the 0–20 cm layer compared to the 40–80 cm layer. The average salt concentration in the soil at the end of the growth period was significantly higher than before transplantation, and this phenomenon became more pronounced with increasing salinity levels. Initial irrigation with brackish water with a salinity level of 2–4 g·L−1 promoted the growth of the tomatoes planted in the spring and the plant height and stem diameter reached the peak values of 1.68 m and 1.08 mm for the T2 treatment, respectively, which were 7.1% and 9.2% higher than that of the CK treatment, ensuring efficient yield and water usage. However, continuous irrigation with brackish water with a salinity level of 2–4 g·L−1 inhibited the growth and yield of the tomatoes planted in autumn, while the T1 and T2 treatments only yielded 24,427.42 and 16,774.86 kg·hm−2, respectively, showing a decline of 32.2% and 46.1% compared to the yields of the spring season. Considering the soil water-salt and yield indicators, under the conditions of non-continuous brackish water irrigation, using water with a salinity level of 2–4 g·L−1 is recommended for drip irrigation of protected tomatoes.

Abstract Background Glutathione (GSH) is important for plants to resist abiotic stress, and a large amount of energy is required in the process. However, it is not clear how the energy status affects the accumulation of GSH in plants under cold stress. Results Two rice pure lines, Zhongzao39 (ZZ39) and its recombinant inbred line 82 (RIL82) were subjected to cold stress for 48 h. Under cold stress, RIL82 suffered more damages than ZZ39 plants, in which higher increases in APX activity and GSH content were showed in the latter than the former compared with their respective controls. This indicated that GSH was mainly responsible for the different cold tolerance between these two rice plants. Interestingly, under cold stress, greater increases in contents of carbohydrate, NAD(H), NADP(H) and ATP as well as the expression levels of GSH1 and GSH2 were showed in RIL82 than ZZ39 plants. In contrast, ATPase content in RIL82 plants was adversely inhibited by cold stress while it increased significantly in ZZ39 plants. This indicated that cold stress reduced the accumulation of GSH in RIL82 plants mainly due to the inhibition on ATP hydrolysis rather than energy deficit. Conclusion We inferred that the energy status determined by ATP hydrolysis involved in regulating the cold tolerance of plants by controlling GSH synthesis.

Breast cancer, as the common malignant carcinoma in women, seriously reduces the life quality and increases mortality of female worldwide. Fortunately, insufficient chemotherapy with external photothermal therapy could remarkably improve the therapeutic efficiency of breast cancer. In this work, we proposed a polydopamine (PDA) and tetrasulfide bond co-doped hollowed mesoporous silica nanospheres with Dox loading and surface hyaluronic acid coating for drug leakage avoidance (PhMSON@Dox-HA). After intravenously injected into tumor bearing-mice, this therapeutic agent could effectively target to the tumor site owing to the HA modification. The biocompatible property and GSH-induced decomposition capability endows the precise release of drugs in the cytoplasm of tumor cells. Meanwhile, PDA facilitated the efficient photothermal therapy under 808 nm laser irradiation. Therefore, the synergistic effect of chemo-photothermal therapy possessed most effective tumor eradication ability. Our work exploits the design approach of biocompatible and degradable drug delivery nanocarriers and sheds bright light on the chemotherapy and photothermal therapy combination for the malignant tumor elimination.

Milk fatty acids are essential for many dairy product productions, while intramuscular fat (IMF) is associated with the quality of meat. The triacylglycerols (TAGs) are the major components of IMF and milk fat. Therefore, understanding the polymorphisms and genes linked to fat synthesis is important for animal production. Identifying quantitative trait loci (QTLs) and genes associated with milk and meat production traits has been the objective of various mapping studies in the last decade. Consistently, the QTLs on chromosomes 14, 15, and 9 have been found to be associated with milk and meat production traits in cattle, goat, and buffalo and sheep, respectively. Diacylglycerol O-acyltransferase 1 (DGAT1) gene has been reported on chromosomes 14, 15, and 9 in cattle, goat, and buffalo and sheep, respectively. Being a key role in fat metabolism and TAG synthesis, the DGAT1 has obtained considerable attention especially in animal milk production. In addition to milk production, DGAT1 has also been a subject of interest in animal meat production. Several polymorphisms have been documented in DGAT1 in various animal species including cattle, buffalo, goat, and sheep for their association with milk production traits. In addition, the DGAT1 has also been studied for their role in meat production traits in cattle, sheep, and goat. However, very limited studies have been conducted in cattle for association of DGAT1 with meat production traits in cattle. Moreover, not a single study reported the association of DGAT1 with meat production traits in buffalo; thus, further studies are warranted to fulfill this huge gap. Keeping in view the important role of DGAT1 in animal production, the current review article was designed to highlight the major development and new insights on DGAT1 effect on milk and meat production traits in cattle, buffalo, sheep, and goat. Moreover, we have also highlighted the possible future contributions of DGAT1 for the studied species.

CeO2-based nanoenzymes present a very promising paradigm in cancerous therapy, as H2O2 can be effectively decomposed under the electron transmit between Ce3+ and Ce4+. However, the limitations of endogenous H2O2 and intracellular low Fenton-like reaction rate lead to single unsatisfied chemodynamic therapy (CDT) efficacy. Other therapeutic modalities combined with chemodynamic therapy are generally used to enhance the tumor eradiation efficacy. Here, we have synthesized a novel hollow pH-sensitive CeO2 nanoenzyme after a cavity is loaded with indocyanine green (ICG), as well as with surface modification of tumor targeting peptides, Arg-Gly-Asp (denoted as HCeO2@ICG-RGD), to successfully target tumor cells via αvβ3 recognition. Importantly, in comparison with single chemodynamic therapy, a large amount of reactive oxygen species in cytoplasm were induced by enhanced chemodynamic therapy with photothermal therapy (PTT). Furthermore, tumor cells were efficiently killed by a combination of photothermal and chemodynamic therapy, revealing that synergistic therapy was successfully constructed. This is mainly due to the precise delivery of ICG and release after HCeO2 decomposition in cytoplasm, in which effective hyperthermia generation was found under 808 nm laser irradiation. Meanwhile, our HCeO2@ICG-RGD can act as a fluorescent imaging contrast agent for an evaluation of tumor tissue targeting capability in vivo. Finally, we found that almost all tumors in HCeO2@ICG-RGD+laser groups were completely eradicated in breast cancer bearing mice, further proving the effective synergistic effect in vivo. Therefore, our novel CeO2-based PTT agents provide a proof-of-concept argumentation of tumor-precise multi-mode therapies in preclinical applications.

Mastitis (inflammation of the mammary gland) commonly occurs in dairy cattle during the periparturient period (transition period), in which dairy cattle experience physiological and hormonal changes and severe negative energy balance, followed by oxidative stress. To maintain successful lactation and combat negative energy balance (NEB), excessive fat mobilization occurs, leading to overproduction of reactive oxygen species (ROS). Excessive fat mobilization also increases the concentrations of nonesterified fatty acids (NEFA) and β-hydroxybutyric acid (BHB) during the periparturient period. In addition, the excessive utilization of oxygen by cellular respiration in the mammary causes abnormal production of oxidative stress (OS). OS impairs the immunity and anti-inflammatory efficiency of periparturient dairy cattle, increasing their susceptibility to mastitis. To alleviate oxidative stress and subsequent mastitis, antioxidants are supplemented to dairy cattle from an external source. Extensive studies have been conducted on the supplementation of selenium (Se) and vitamins E and B9 to mitigate mastitis during the transition period in dairy cattle. Altogether, in the current review, we discuss the research development on bovine mastitis and its major causes, with special emphasis on oxidative stress during the transition period. Moreover, we discuss the antioxidant, immunoregulatory, and anti-inflammatory properties of Se and vitamins E and B9 and their role in the control of bovine mastitis in periparturient dairy cattle.

Dairy cattle experience health risks during the periparturient period. The continuous overproduction of reactive oxygen species (ROS) during the transition from late gestation to peak lactation leads to the development of oxidative stress. Oxidative stress is usually considered the main contributor to several diseases such as retained placenta, fatty liver, ketosis, mastitis and metritis in periparturient dairy cattle. The oxidative stress is generally balanced by the naturally available antioxidant system in the body of dairy cattle. However, in some special conditions, such as the peripariparturient period, the natural antioxidant system of a body is not able to balance the ROS production. To cope with this situation, the antioxidants are supplied to the dairy cattle from external sources. Natural antioxidants such as selenium and vitamin E have been found to restore normal health by minimizing the harmful effects of excessive ROS production. The deficiencies of Se and vitamin E have been reported to be associated with various diseases in periparturient dairy cattle. Thus in the current review, we highlight the new insights into the Se and vitamin E supplementation as antioxidant agents in the health regulation of periparturient dairy cattle.

Camel milk is a rich source of vitamin C, lactic acid bacteria (LAB), beta-caseins and milk whey proteins, including lactoferrin, lysozyme, lactoperoxidase, alpha-lactalbumin and immunoglobulin. The lactoferrin plays a key role in several physiological functions, such as conferring antioxidant, anti-microbial and anti-inflammatory functions in cells. Similarly, the camel milk alpha-lactalbumin has shown greater antioxidative activity because of its higher antioxidant amino acid residues. The antioxidant properties of camel milk have also been ascribed to the structural conformation of its beta-caseins. Upon hydrolysis, the beta-caseins lead to some bioactive peptides having antioxidant activities. Consequently, the vitamin C in camel milk has a significant antioxidant effect and can be used as a source of vitamin C when the climate is harsh. Furthermore, the lysozyme and immunoglobulins in camel milk have anti-microbial and immune regulatory properties. The LAB isolated from camel milk have a protective role against both Gram-positive and -negative bacteria. Moreover, the LAB can be used as a probiotic and may restore the oxidative status caused by various pathogenic bacterial infections. Various diseases such as cancer and hepatitis have been associated with oxidative stress. Camel milk could increase antiproliferative effects and regulate antioxidant genes during cancer and hepatitis, hence ameliorating oxidative stress. In the current review, we have illustrated the anti-microbial and antioxidant properties of camel milk in detail. In addition, the anti-cancer and anti-hepatitis properties of camel milk have also been discussed.

The cytokine-activated Janus kinase (JAK)—signal transducer and activator of transcription (STAT) pathway is a sequence of communications between proteins in a cell, and it is associated with various processes such as cell division, apoptosis, mammary gland development, lactation, anti-inflammation, and immunity. The pathway is involved in transferring information from receptors on the cell surface to the cell nucleus, resulting in the regulation of genes through transcription. The Janus kinase 2 (JAK2), signal transducer and activator of transcription A and B (STAT5 A & B), STAT1, and cytokine signaling suppressor 3 (SOCS3) are the key members of the JAK-STAT pathway. Interestingly, prolactin (Prl) also uses the JAK-STAT pathway to regulate milk production traits in dairy cattle. The activation of JAK2 and STATs genes has a critical role in milk production and mastitis resistance. The upregulation of SOCS3 in bovine mammary epithelial cells inhibits the activation of JAK2 and STATs genes, which promotes mastitis development and reduces the lactational performance of dairy cattle. In the current review, we highlight the recent development in the knowledge of JAK-STAT, which will enhance our ability to devise therapeutic strategies for bovine mastitis control. Furthermore, the review also explores the role of the JAK-STAT pathway in the regulation of milk production in dairy cattle.

Mastitis is the inflammation of the mammary gland. Escherichia coli and Staphylococcus aureus are the most common bacteria responsible for mastitis. When mammary epithelial cells are infected by microorganisms, this activates an inflammatory response. The bacterial infection is recognized by innate pattern recognition receptors (PRRs) in the mammary epithelial cells, with the help of Toll-like receptors (TLRs). Upon activation by lipopolysaccharides, a virulent agent of bacteria, the TLRs further trigger nuclear factor-κB (NF-κB) signaling to accelerate its pathogenesis. The NF-κB has an essential role in many biological processes, such as cell survival, immune response, inflammation and development. Therefore, the NF-κB signaling triggered by the TLRs then regulates the transcriptional expression of specific inflammatory mediators to initiate inflammation of the mammary epithelial cells. Thus, any aberrant regulation of NF-κB signaling may lead to many inflammatory diseases, including mastitis. Hence, the inhibiting of NF-κB signaling has potential therapeutic applications in mastitis control strategies. In this review, we highlighted the regulation and function of NF-κB signaling in mastitis. Furthermore, the role of NF-κB signaling for therapeutic purposes in mastitis control has been explored in the current review.

The aim of this study was to evaluate the effects of pair versus individual housing on performance, health, and behavior of dairy calves. Thirty female Holstein dairy calves were assigned to individual (n = 10) or pair housing (n = 10 pairs). The results showed that both treatments had a similar starter intake and average daily gain (ADG) during the preweaning period. During weaning and postweaning periods, paired calves had a higher starter intake, and the ADG of paired calves continued to increase but calves housed individually experienced a growth check. Paired calves showed higher diarrhea frequency only in week three. The results on behavior showed that feeding, chewing and ruminating time increased, and self-grooming time decreased with age during weaning and postweaning periods, and paired calves spent less time feeding, standing and self-grooming but more time lying during this time. After mixing, feeding, and chewing and ruminating time continued to rise, and self-grooming time continued to decline for both treatments. All calves spent less time standing and non-nutritive manipulation after mixing, and previously individually housed calves tended to increase non-nutritive manipulation. These results showed that pair housing improved growth during weaning and postweaning periods and that calves altered their behavior at different phases. Less social contact may lead to more non-nutritive manipulation.

In this article, we consider the following a class of Schrödinger-Poisson systems with p-Laplacian in R3 of the form:... where... is the p-Laplacian operator, λ is a positive parameter. Assume that the nonnegative function b possesses a potential well int(b-1{f0g}), which is composed of k disjoint components... and consider the nonlinearity g with subcritical growth. Using the variational methods and Morse iteration technique, the existence of positive multibump solutions are obtained. [ABSTRACT FROM AUTHOR]

Abstract Anti-PD-1 antibodies are a favorable treatment for relapsed or refractory extranodal natural killer T cell lymphoma (RR-ENKTL), however, the complete response (CR) rate and the duration of response (DOR) need to be improved. This phase 1b/2 study investigated the safety and efficacy of sintilimab, a fully human anti-PD-1 antibody, plus chidamide, an oral subtype-selective histone deacetylase inhibitor in 38 patients with RR-ENKTL. Expected objective response rate (ORR) of combination treatment was 80%. Patients received escalating doses of chidamide, administered concomitantly with fixed-dose sintilimab in 21-days cycles up to 12 months. No dose-limiting events were observed, RP2D of chidamide was 30 mg twice a week. Twenty-nine patients were enrolled in phase 2. In the intention-to-treat population (n = 37), overall response rate was 59.5% with a complete remission rate of 48.6%. The median DOR, progression-free survival (PFS), and overall survival (OS) were 25.3, 23.2, and 32.9 months, respectively. The most common grade 3 or higher treatment-emergent adverse events (AEs) were neutropenia (28.9%) and thrombocytopenia (10.5%), immune-related AEs were reported in 18 (47.3%) patients. Exploratory biomarker assessment suggested that a combination of dynamic plasma ctDNA and EBV-DNA played a vital prognostic role. STAT3 mutation shows an unfavorable prognosis. Although outcome of anticipate ORR was not achieved, sintilimab plus chidamide was shown to have a manageable safety profile and yielded encouraging CR rate and DOR in RR-ENKTL for the first time. It is a promising therapeutic option for this population.