Chlorine bridge bond-enabled binuclear copper complex for electrocatalyzing lithium-sulfur reactions.

Engineering atom-scale sites are crucial to the mitigation of polysulfide shuttle, promotion of sulfur redox, and regulation of lithium deposition in lithium-sulfur batteries. Herein, a homonuclear copper dual-atom catalyst with a proximal distance of 3.5 Å is developed for lithium-sulfur batteries, wherein two adjacent copper atoms are linked by a pair of symmetrical chlorine bridge bonds. Benefiting from the proximal copper atoms and their unique coordination, the copper dual-atom catalyst with the increased active interface concentration synchronously guide the evolutions of sulfur and lithium species. Such a delicate design breaks through the activity limitation of mononuclear metal center and represents a catalyst concept for lithium-sulfur battery realm. Therefore, a remarkable areal capacity of 7.8 mA h cm-2 is achieved under the scenario of sulfur content of 60 wt.%, mass loading of 7.7 mg cm-2 and electrolyte dosage of 4.8 µL mg-1.

Alpha-Melanocyte-Stimulating Hormone-Mediated Appetite Regulation in the Central Nervous System.

Understanding the complex action mechanism of appetite regulation peptides can significantly impact therapeutic options in the treatment of obesity and other metabolic diseases. Hypothalamic alpha-melanocyte-stimulating hormone (α-MSH) is an anorexigenic peptide, closely related to the occurrence of obesity, playing a central role in food intake and energy expenditure. In the central nervous system, α-MSH is cleaved from proopiomelanocortin and then released into different hypothalamic regions to act on melanocortin 3/4 receptor-expressing neurons, lowering food intake, and raising energy expenditure via appetite suppression and sympathetic nervous system. Furthermore, it can increase the transmission of some anorexigenic hormones (e.g., dopamine) and interact with other orexigenic factors (e.g., agouti-related protein, neuropeptide Y) to influence food reward rather than merely feeding behavior. Therefore, α-MSH is a critical node of the hypothalamus in transmitting appetite suppression signals and is a key component of the central appetite-regulating circuits. Herein, we describe the role of α-MSH in appetite suppression in terms of specific receptors, effector neurons, sites of action, and the interaction with other appetite-relative peptides, respectively. We focus on the role of α-MSH in obesity. The status of research on α-MSH-related drugs is also discussed. With the intention of illuminating a new approach for targeting α-MSH in the hypothalamus as a strategy to manage obesity, we hope to further understand the direct or indirect mechanisms by which α-MSH exerts its appetite-regulating effects.

Recent Research Progress on Natural Stilbenes in Dendrobium Species.

Dendrobium is the second biggest genus in the Orchidaceae family, and many of them have been utilized as a traditional Chinese medicine (TCM) for thousands of years in China. In the last few decades, constituents with great chemical diversity were isolated from Dendrobium, and a wide range of biological activities were detected, either for crude extracts or for pure compounds. Stilbene compound is one of the primary active constituents in the genus Dendrobium. At present, 267 stilbene compounds with clarified molecular structures have been extracted and isolated from 52 species of Dendrobium, including 124 phenanthrenes and 143 bibenzyls. At the same time, activity studies have indicated that 157 compounds have pharmaceutical activity. Among them, most of the compounds showed antitumor activity, followed by antioxidant, anti-inflammatory and anti-α-glucosidase inhibitory activities. Additionally, 54 compounds have multiple pharmacological activities, such as confusarin (14), 2,4,7-trihydroxy-9,10-dihydro-phenanthrene (43), moscatilin (148), gigantol (150) and batatasin III (151). This review summarizes current knowledge about the chemical composition of stilbene, bioactivities and pharmacologic effects in 52 species of Dendrobium. We also expect to provide a reference for further research, development and utilization of stilbene constituents in the Dendrobium genus.

In-plane strain engineering in ultrathin noble metal nanosheets boosts the intrinsic electrocatalytic hydrogen evolution activity.

Strain has been shown to modulate the electronic structure of noble metal nanomaterials and alter their catalytic performances. Since strain is spatially dependent, it is challenging to expose the active strained interfaces by structural engineering with atomic precision. Herein, we report a facile method to manipulate the planar strain in ultrathin noble metal nanosheets by constructing amorphous-crystalline phase boundaries that can expose the active strained interfaces. Geometric-phase analysis and electron diffraction profile demonstrate the in-plane amorphous-crystalline boundaries can induce about 4% surface tensile strain in the nanosheets. The strained Ir nanosheets display substantially enhanced intrinsic activity toward the hydrogen evolution reaction electrocatalysis with a turnover frequency value 4.5-fold higher than the benchmark Pt/C catalyst. Density functional theory calculations verify that the tensile strain optimizes the d-band states and hydrogen adsorption properties of the strained Ir nanosheets to improve catalysis. Furthermore, the in-plane strain engineering method is demonstrated to be a general approach to boost the hydrogen evolution performance of Ru and Rh nanosheets.

Crystal Plane Reconstruction and Thin Protective Coatings Formation for Superior Stable Zn Anodes Cycling 1300 h.

Some new insights into traditional metal pretreatment of anticorrosion for high stable Zn metal anodes are provided. A developed pretreatment methodology is employed to prefer the crystal plane of polycrystalline Zn and create 3.26 µm protective coatings mainly consisting of organic polymers and zinc salts on Zn foils (ROZ@Zn). In this process, Zn metal exhibits a surface-preferred (001) crystal plane proved by electron backscattered diffraction. Preferred (001) crystal planes and ROZ coatings can regulate Zn2+ diffusion, promote flat growth of Zn, and prevent side reactions. As a result, ROZ@Zn symmetrical cells exhibit superior plating/stripping performance over 1300 h. Impressively, it is significantly prolonged over 40 times in comparison to the bare Zn symmetric cell at 5 mA cm-2 . Moreover, Zn//MnO2  button cells have a high capacity retention of 96.3% after 1600 cycles and pouch cells have a high capacity 122 mAh g-1  after 200 cycle at 5 C. This work provides inspiration for high stable aqueous Zn metal batteries using the developed metal pretreatment of anticorrosion, which will be a viable, low-cost, and efficient technology. More interesting, it demonstrates the availability of reconstructing crystal planes by the largely heterogeneous reaction activation of the different crystal planes to H+ .

Reversing the Nucleophilicity of Active Sites in CoP2 Enables Exceptional Hydrogen Evolution Catalysis.

Precisely constructing the local configurations of active sites to achieve on-demand catalytic functions is highly critical yet challenging. Herein, an anion-deficient strategy to precisely capture Ru single atoms on the anion vacancies of CoP2 (Ru-SA/Pv-CoP2 ) is developed. Refined structural characterizations reveal that the Ru single atoms preferably bind to the anion vacancy sites and consequently build a superior catalytic surface with neighboring CoP and CoRu coordination states for the hydrogen evolution reaction (HER) catalysis. The prepared Ru-SA/Pv-CoP2 nanowires exhibit an unprecedented overpotential of 17 mV at 10 mA cm-2geo , and the corresponding mass activity is 52.2 times higher than the benchmark Pt/C catalyst at the overpotential of 50 mV. Theoretical analysis illustrates that the introduced Ru-SAs can reverse electrons state distribution (from nucleophilic P sites to electrophilic Ru sites) and boost the activation of water molecules and hydrogen production. More importantly, such a construction strategy is also applicable for Pt single atom coupling, suggesting its generality in building catalytic sites. The capability to precisely construct active sites offers a powerful platform to manipulate the catalytic performance of HER catalysts and beyond.

Ergosterol peroxide: an effect-directed detecting method from Anoectochilus elwesii and evaluation of anticancer activity.

Ergosterol peroxide (EP) in Anoectochilus elwesii possesses antioxidant and anticancer properties, yet few studies have been focused on its mechanisms and directed detecting. By practicing HPTLC-DPPH coupled with UHPLC-ESI-TOF MS, EP was located and the cytotoxic activity of EP was performed by MTT method. The apoptosis studies were conducted on SGC-7901cells by AO/EB and Annex V/PI staining method, PI flow cytometric assay, reactive oxygen species detection and mitochondrial membrane potential assay. An effect-directed detecting method of HPTLC-DPPH/UHPLC/ESI-TOF-MS was developed for EP rapidly and precisely, providing an option for identifying oxidative compounds. EP exhibits high cytotoxic activity against SGC-7901 gastric cancer cells and the morphological apoptosis suggested that EP induced apoptosis and cell cycle arrest in G0/G1 phase. It could enhance the ROS level and cause a decrease in the mitochondrial membrane potential. Its antiproliferative mechanism is G0/G1 phase arrest and might be traced through ROS-mediated mitochondrial dysfunction pathways.

Ameliorating effect on glycolipid metabolism and chemical profile of Millettia speciosa champ. extract.

ETHNOPHARMACOLOGICAL RELEVANCE: Millettia speciosa Champ., also called Niu dali, is a fabaceous medicinal plant mainly distributed in southeast China, where it is a functional food for developing physical strength, and often used traditionally in medicinal treatment of numbness of the wrists, diabetes, hepatitis, and so on. AIM OF THE STUDY: To investigate the chemical profile, ameliorating effects of MSC on glycolipid metabolism in diabetic mice and to identify the possible mechanism of action. MATERIALS AND METHODS: High-performance liquid chromatography coupled with electrospray ionization quadrupole time of flight mass spectrometry (HPLC-ESI-QTOF-MS) was applied to analyze the chemical compositions from M. speciosa extract (MSC). MSC was orally administered to high-fat diet and STZ-induced diabetic mice at doses of 4.55, 9.10 and 13.65 mg/(kg·d) respectively for 10 weeks. Indices of glycolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI), blood lipids, HPA-axis hormones, and related gene expressions were evaluated. RESULTS: 86 compounds were tentatively identified from MSC, counting for 91.97% of the total extract, mainly including 23 alkaloids (including 2 cyanogenetic glycosides firstly identified in this species, total content accounted to 39.71%), 23 flavonoids (11.91%), 17 acids (including 3 amino acids, 9 phenolic acids and 5 organic acids; 9.2%), 9 terpenoids and steroids (20.13%), 7 esters (3.33%), 3 lignans (3.73%), 3 saccharides (4.0%) and 1 anthraquinone (0.18%). MSC could ameliorate the glycolipid disorder in diabetic mice markedly, and significant regulations on CRH and ACTH hormones were observed. Moreover, the cellular morphology of liver and pancreas were significantly improved and the expressions of IRS2, PI3K, Akt and GLUT4 were significantly up-regulated by MSC treatment. CONCLUSION: This was the first time to study the chemical profile and ameliorating effect on glycolipid metabolism of M. speciosa. It was found to be rich in flavonoids and alkaloids, which might support the potential relation of material foundation and the activity in regulating glycolipid metabolism. The ameliorating effect on glycolipid disorder in diabetic mice might be associated to the regulation of related hormones of the HPA axis and the IRS2/PI3K/Akt/GLUT4 signalling pathway. It was of great significance for advanced directed separation and pharmacological activity research of MSC.

Comprehensive chemical analysis of Zhenshu Tiaozhi formula and its effect on ameliorating glucolipid metabolic disorders in diabetic rats.

The present study aims to reveal the compositions of Zhenshu TiaoZhi formula (FTZ) comprehensively, and investigate whether FTZ ameliorate glucolipid metabolism disorders in diabetic rats with the involvement of glucocorticoids in peripheral insulin-sensitive tissues. The fingerprint was established based on 11 batches of FTZ samples and chemical compostions of FTZ were identified by ultra performance liquid chromatography-time of flight/mass spectrometry (UPLC-TOF/MS). High-fat diet (HFD) and streptozotocin (STZ) induced diabetic rats were orally administrated with 3 and 6 g/kg body weight of FTZ for 8 weeks. Indices of glucolipid metabolism, including fasting blood glucose (FBG), fasting insulin, insulin resistance index (IRI) and blood lipids were evaluated after treatment of FTZ. The levels of HPA axis hormones were examined. Reverse transcription-polymerase chain reaction (RT-PCR) was adopted to investigate the relative mRNA expressions of 11ß-hydroxysteroid dehydrogenase 1 (11ß-HSD1) and glucolipid metabolic indicators. A reference fingerprint was established and 93 compounds of FTZ were tentatively identified. In vivo, FTZ treatment exerted antidiabetic and antidyslipidemic effects while decreased the level of corticotropin releasing hormone (CRH). 11ß-HSD1 mRNA showed similar trajectory in both liver, adipose and skeletal muscle tissues, which was up-regulated in diabetic group and ameliorated in FTZ groups. Furthermore, the expressions of glucose-6-phosphatase (G6Pase), phosphoenolpyruvate carboxykinase (PEPCK) and adipose triglyceride lipase (ATGL) were down-regulated in liver and skeletal muscle. These results elucidated the compositions of FTZ comprehensively and indicated its effect on ameliorating glucolipid metabolism of diabetic rats involved hypothalamus-pituitary-adrenal (HPA) axis homeostasis. Down-regulating 11ß-HSD1 in insulin-sensitive tissues might be a potential mechanism of FTZ in treating type 2 diabetes mellitus (T2DM).

Hypothalamus-pituitary-adrenal Axis in Glucolipid metabolic disorders.

With the change of life style, glucolipid metabolic disorders (GLMD) has become one of the major chronic disorders causing public health and clinical problems worldwide. Previous studies on GLMD pay more attention to peripheral tissues. In fact, the central nervous system (CNS) plays an important role in controlling the overall metabolic balance. With the development of technology and the in-depth understanding of the CNS, the relationship between neuro-endocrine-immunoregulatory (NEI) network and metabolism had been gradually illustrated. As the hub of NEI network, hypothalamus-pituitary-adrenal (HPA) axis is important for maintaining the balance of internal environment in the body. The relationship between HPA axis and GLMD needs to be further studied. This review focuses on the role of HPA axis in GLMD and reviews the research progress on drugs for GLMD, with the hope to provide the direction for exploring new drugs to treat GLMD by taking the HPA axis as the target and improve the level of prevention and control of GLMD.

Hexagonal Boron Nitride as a Multifunctional Support for Engineering Efficient Electrocatalysts toward the Oxygen Reduction Reaction.

Developing heterostructures with well-defined interfaces is attracting ever-increasing interest toward the development of advanced electrocatalysts. Herein, hexagonal boron nitride (h-BN) nanosheets are reported as a multifunctional support for constructing efficient electrocatalysts for the oxygen reduction reaction (ORR). h-BN/Pd heterostructured electrocatalysts with decent activity and long-term durability are designed and synthesized by confining Pd nanoparticles (NPs) on ultrathin h-BN nanosheets. The robust h-BN serves as a durable platform to maintain the structural integrity of the heterostructured catalysts. Both experimental findings and theoretical calculations reveal that the strong interaction between h-BN and Pd downshifts the Pd d-band center and hence optimizes the affinity with the reaction intermediates. Meanwhile, h-BN also endows the heterostructured catalysts with superhydrophobic surfaces, promoting the diffusion kinetics of O2. These findings open a new avenue for the rational design and development of heterostructured catalysts by interface engineering toward electrocatalysis applications.

Regulating the Interfacial Electronic Coupling of Fe2 N via Orbital Steering for Hydrogen Evolution Catalysis.

The capability of manipulating the interfacial electronic coupling is the key to achieving on-demand functionalities of catalysts. Herein, it is demonstrated that the electronic coupling of Fe2 N can be effectively regulated for hydrogen evolution reaction (HER) catalysis by vacancy-mediated orbital steering. Ex situ refined structural analysis reveals that the electronic and coordination states of Fe2 N can be well manipulated by nitrogen vacancies, which impressively exhibit strong correlation with the catalytic activities. Theoretical studies further indicate that the nitrogen vacancy can uniquely steer the orbital orientation of the active sites to tailor the electronic coupling and thus benefit the surface adsorption capability. This work sheds light on the understanding of the catalytic mechanism in real systems and could contribute to revolutionizing the current catalyst design for HER and beyond.

N-induced lattice contraction generally boosts the hydrogen evolution catalysis of P-rich metal phosphides.

P-rich transition metal phosphides (TMPs) with abundant P sites have been predicted to be more favorable for hydrogen evolution reaction (HER) catalysis. However, the actual activities of P-rich TMPs do not behave as expected, and the underlying essence especially at the atomic level is also ambiguous. Our structural analysis reveals the inferior activity could stem from the reduced overlap of atomic wave functions between metal and P with the increase in P contents, which consequently results in too strong P-H interaction. To this end, we used N-induced lattice contraction to generally boost the HER catalysis of P-rich TMPs including CoP2, FeP2, NiP2, and MoP2. Refined structural characterization and theoretical analysis indicate the N-P strong interaction could increase the atomic wave function overlap and eventually modulate the H adsorption strength. The concept of lattice engineering offers a new vision for tuning the catalytic activities of P-rich TMPs and beyond.

Facile Fabrication of N-Doped TiO2 Nanoparticles/Carbon Composite with Excellent Electrochemical Properties for Lithium Ion Batteries.

A promising anode material for lithium-ion batteries (LIBs) consisting of ultrafine N-doped TiO2 nanoparticles and N-doped carbon composite has been prepared by an effective sol-gel-calcined strategy. The synergetic effect between N-doped TiO2 nanoparticles and N-doped carbon provides not only high conductivity paths and strong electron contact interface, but also supply a large surface area along with hindering the nanoparticles aggregation, resulting in excellent lithium-storage performance. When tested as an anode material for LIBs, a high capacity of 292.7 mAh g-1 can be retained after 50 cycles at 0.5 C. Even at 8 C, a satisfactory capacity of 160.3 mAh g-1 can be delivered. These features suggest the N-doped TiO2/C composite a viable choice for application as an anode material in high-power LIBs.

In2O3 Nanocrystals for CO2 Fixation: Atomic-Level Insight into the Role of Grain Boundaries.

N-functionalization of amines with CO2 and H2 is one of the most important processes to make use of CO2. Although noble metal-based catalysts with remarkable performance have been widely used in this process, developing efficient non-noble-metal-based catalysts remains a grand challenge. Herein, we report In2O3 nanocrystals with high density of grain boundaries (HGB-In2O3), which show excellent activity toward methylation of amines. Impressively, HGB-In2O3 achieved the optimal yield of 82.7% for N,N-dimethylaniline with a mass activity of 21.2 mmol·g-1h-1 in methylation of N-methylaniline, comparable to noble-metal-based catalysts. As a bonus, HGB-In2O3 held noticeable stability, remarkable selectivity, and comprehensive applicability. Further mechanistic studies revealed that the presence of high density of grain boundaries not only facilitated the adsorption and activation of CO2 to generate CH3OH as the intermediate but also enhanced the activation of N-H bond in amines, contributing to the attractive activity of HGB-In2O3 toward methylation of amines.

Chinese Medicine FTZ Recipe Protects against High-Glucose-Induced Beta Cell Injury through Alleviating Oxidative Stress.

OBJECTIVE: To investigate the effect of FTZ on high-glucose-induced oxidative stress and underlying mechanisms. METHODS: We used a ß cell dysfunction and diabetes model that was induced in rats fed a high-fat high-sugar diet (HFHSD) for 6 weeks and injected once with 35 mg/kg streptozocin (STZ). Then, 3 and 6 g/kg of FTZ were administered by gavage for 8 weeks. In addition, an ex vivo model of oxidative stress was induced by stimulating INS-1 cells with 25 mmol/L glucose for 48 h. RESULT: The levels of fasting blood glucose (FBG) in diabetic model rats were obviously higher than those in the normal group; furthermore with reduced levels of ß cells, catalase (CAT), superoxide dismutase (SOD), and Bcl-2 increased lipid peroxide malondialdehyde (MDA) and caspase-3 in the pancreatic tissue of the diabetic model rats. Afterward, the cells were incubated with FTZ-containing serum and edaravone. The 25 mmol/L glucose-induced SOD reduction increased MDA and intracellular ROS. The protein expression level of Mn-SOD and CAT in the model group decreased significantly compared with that in the control group. CONCLUSION: FTZ treatment significantly improved the alteration in the level of SOD, CAT, Bcl-2, caspase-3, and MDA coupled with ß cell dysfunction in diabetic rats. Oxidative stress in INS-1 cells was closely associated with a higher rate of apoptosis, increased production of ROS and MDA, enhanced Bax expression, and caspase-3, -9 activities and markedly decreased protein expression of Mn-SOD and CAT. FTZ-containing serum incubation notably reversed the high-glucose-evoked increase in cell apoptosis, production of ROS and MDA, and Bax protein levels. Furthermore, FTZ stimulation upregulated the expression levels of several genes, including Mn-SOD, CAT, and Bcl-2/Bcl-xl. In addition, FTZ decreased the intracellular activity of caspase-3, -9 in INS-1 cells. FTZ protected ß-cells from oxidative stress induced by high glucose in vivo and in vitro. The beneficial effect of FTZ was closely associated with a decrease in the activity of caspase-3, -9 and intracellular production of ROS, MDA, and Bax coupled with an increase in the expression of Mn-SOD, CAT, and Bcl-2/Bcl-xl.

Tuning orbital orientation endows molybdenum disulfide with exceptional alkaline hydrogen evolution capability.

Molybdenum disulfide is naturally inert for alkaline hydrogen evolution catalysis, due to its unfavorable water adsorption and dissociation feature originated from the unsuitable orbital orientation. Herein, we successfully endow molybdenum disulfide with exceptional alkaline hydrogen evolution capability by carbon-induced orbital modulation. The prepared carbon doped molybdenum disulfide displays an unprecedented overpotential of 45 mV at 10 mA cm-2, which is substantially lower than 228 mV of the molybdenum disulfide and also represents the best alkaline hydrogen evolution catalytic activity among the ever-reported molybdenum disulfide catalysts. Fine structural analysis indicates the electronic and coordination structures of molybdenum disulfide have been significantly changed with carbon incorporation. Moreover, theoretical calculation further reveals carbon doping could create empty 2p orbitals perpendicular to the basal plane, enabling energetically favorable water adsorption and dissociation. The concept of orbital modulation could offer a unique approach for the rational design of hydrogen evolution catalysts and beyond.

Boosting Water Dissociation Kinetics on Pt-Ni Nanowires by N-Induced Orbital Tuning.

Although it is commonly believed that the water-dissociation-related Volmer process is the rate-limiting step for alkaline hydrogen evolution reaction (HER) on Pt-based catalysts, the underlying essence, particularly on the atomic scale, still remains unclear. Herein, it is revealed that the sluggish water-dissociation behavior probably stems from unfavorable orbital orientation and the kinetic issue is successfully resolved via N-induced orbital tuning. Impressively, N modified Pt-Ni nanowires deliver an ultralow overpotential of 13 mV at 10 mA cm-2 , which represents a new benchmark for alkaline HER catalysis. Fine-structural characterization and density functional theory analysis illustrate that the introduced nitrogen can uniquely modulate the electron densities around the Ni sites, and further create empty dz 2 orbitals with superior orientation for water adsorption and activation. More importantly, it is demonstrated that N-induced orbital modulation can generally boost the alkaline HER activities of Pt-Co, Pt-Ni, and Pt-Cu, offering a new perspective for the design of HER catalysts and beyond.

A new furostanol saponin from Dendrobium chrysanthum Lindl. with cytotoxic activity.

A new furostanol saponin, (25R)-26-O-(α-d-glucopyranosyl)-(1→2)-α-l-rhamnopyranosyl-furost-5-ene-3ß, 22α, 26-triol-3-O-α-d-glucopyranoside (1), together with four known compounds 2-5 were isolated from the ethanolic extract of the stems of Dendrobium chrysanthum Lindl. The structures of these new compounds were identified by extensive spectroscopic analysis including 1D and 2D NMR and HR-ESI-MS, as well as chemical methods. Compounds 1-3 were isolated from D. chrysanthum for the first time. Furthermore, the inhibitory effects of the compounds on tumor cells were evaluated, and compounds 1-2 exhibited significant cytotoxic activities potentially against SPC-A1, MCF-7 and HeLa human cancer cell lines. Compounds 3-5 showed inhibitory activity against the SPC-A1 and MCF-7.

Electron density modulation of NiCo2S4 nanowires by nitrogen incorporation for highly efficient hydrogen evolution catalysis.

Metal sulfides for hydrogen evolution catalysis typically suffer from unfavorable hydrogen desorption properties due to the strong interaction between the adsorbed H and the intensely electronegative sulfur. Here, we demonstrate a general strategy to improve the hydrogen evolution catalysis of metal sulfides by modulating the surface electron densities. The N modulated NiCo2S4 nanowire arrays exhibit an overpotential of 41 mV at 10 mA cm-2 and a Tafel slope of 37 mV dec-1, which are very close to the performance of the benchmark Pt/C in alkaline condition. X-ray photoelectron spectroscopy, synchrotron-based X-ray absorption spectroscopy, and density functional theory studies consistently confirm the surface electron densities of NiCo2S4 have been effectively manipulated by N doping. The capability to modulate the electron densities of the catalytic sites could provide valuable insights for the rational design of highly efficient catalysts for hydrogen evolution and beyond.