Comparative Efficacy of Micro-Needle-Knife Therapy and Acupuncture in Acute Ankle Sprains: A Randomized Controlled Trial.

BACKGROUND Micro-needle knife (MNK) therapy releases the superficial fascia to alleviate pain and improve joint function in patients with acute ankle sprains (AAS). We aimed to evaluate the efficacy and safety of MNK therapy vs that of acupuncture. MATERIAL AND METHODS This blinded assessor, randomized controlled trial allocated 80 patients with AAS to 2 parallel groups in a 1: 1 ratio. The experimental group received MNK therapy; the control group underwent conventional acupuncture treatment at specified acupoints. Clinical efficacy differences between the 2 groups before (time-point 1 [TP1]) and after treatment (TP2) were evaluated using the visual analogue scale (VAS) and Kofoed ankle score. Safety records and evaluations of adverse events were documented. One-month follow-up after treatment (TP3) was conducted to assess the intervention scheme's reliability. RESULTS VAS and Kofoed ankle scores significantly improved in both groups. No patients dropped due to adverse events. At TP1, there were no significant differences between the 2 groups in terms of VAS and Kofoed scores (P>0.05). However, at TP2, efficacy of MNK therapy in releasing the superficial fascia was significantly superior to that of acupuncture treatment (P<0.001). At TP3, no significant differences in scores existed between the groups (P>0.05). CONCLUSIONS This study demonstrates that 6 sessions of MNK therapy to release the superficial fascia safely and effectively alleviated pain and enhanced ankle joint function in patients with AAS, surpassing the efficacy of conventional acupuncture treatment. Future studies should increase the sample size and introduce additional control groups to further validate the superior clinical efficacy of this intervention.

Fused expression of Sm1-Chit42 proteins for synergistic mycoparasitic response of Trichoderma afroharzianum on Botrytis cinerea.

Sm1 and Chit42 of Trichoderma have been universally confirmed as crucial biocontrol factors against pathogen infection through induced resistance and mycoparasitism, respectively. However, not enough work has been conducted to understand the novel function of fused expression of these two proteins in Trichoderma. The results of this study demonstrated that Sm1-Chit42 protein (SCf) engineered T. afroharzianum strain OE:SCf exerted synergistic inhibition to Botrytis cinerea growth at multiple stages of mycoparasitic interaction of T. afroharzianum and B. cinerea including chemotropism sensing, hyphal coiling, hydrophobicity modulation, cell wall adhesion, virulence reduction and pathogen killing by ROS. These results highlight a novel mycoparasitic system in Trichoderma strains engineered with Sm1-Chit42 chimeric protein to combat B. cinerea growth and reproduction, which would lay a strong foundation for exploring a new engineered Trichoderma biofungicide created with chimeric proteins in the future.

Designing synthetic consortia of Trichoderma strains that improve antagonistic activities against pathogens and cucumber seedling growth.

BACKGROUND: Trichoderma spp. are important agricultural biocontrol microorganisms that are often used as effective components of microbial fungicides and microbial biofertilizers. However, most of these products are prepared by a single strain in monoculture, which significantly limits the biocontrol efficiency and stability of Trichoderma products. Therefore, the establishment of a design and screening approach for consortia with multi-Trichoderma strains for co-culture is of great importance to overcome the shortage of traditional Trichoderma biocontrol products. RESULTS: First, 15 Trichoderma strains were screened in terms of mycelium growth rate, antagonistic activity to a variety of pathogens, stress tolerance to high temperature and salt stress, and cucumber seedling growth promotion level. Then, the combinations of Trichoderma asperellum GDSF1009 (CGMCC NO. 9512), Trichoderma asperelloides Z4-1 (CGMCC NO. 40245), Trichoderma harzianum 10569 (CGMCC NO. 40246), and T. asperellum 10264 (CGMCC NO. 22404) were finally screened as an optimal consortium for co-culture underlying the levels of plant growth-promoting and antagonistic activity to Fusarium oxysporum and seed germination promotion relative to the monoculture of a single strain. Consortia with multiple co-cultured strains were found to generate larger amounts of free amino acids than those from the monoculture of a single strain, and a pot assay also indicated that metabolites of co-cultures were able to promote cucumber seedling growth superior to that with monoculture of a single strain, even though the promotion was better than from simply mixed cultures from each of the four Trichoderma strains. Taken together, the co-culture consortia composed of the four compatible interactive Trichoderma strains was a potential novel multiple strain biocontrol agent based on the combination of synthetic consortia design and co-culture. In the field experiment, we found that the growth-promoting effect of the co-culture fermentation filtrate was better than that of the single culture fermentation filtrate. Compared with T-Z4-1, T-1009, T-10264 and T-10569, the plant height of cucumber was increased by 22.99%, 42.06%, 24.18% and 30.09%, respectively, and the stem diameter was increased by 16.59%, 18.83%, 13.65% and 14.70%, respectively. CONCLUSION: An approach to designing and screening Trichoderma consortia for co-culture was established. The consortia co-culture presented a better performance in antagonistic activity and cucumber growth compared with a monoculture of a single strain. Thus, it is of great significance to lay the foundation for the creation of a novel Trichoderma biofungicide or biomanure to resist cucumber Fusarium wilt and promote cucumber growth.

A Case Report of MODY3 Combined with Intestinal Neuroendocrine Tumor.

Maturity-onset diabetes of the young 3 (MODY3) is an autosomal dominant monogenic diabetes mellitus characterized by defective ß-cell function and non-insulin-dependent early-onset diabetes mellitus. The facts that patients with MODY3 are often misdiagnosed as type 1 and type 2 diabetes mellitus and genetic diagnosis is expensive, make its diagnosis very challenging. In this study, we reported a case of MODY3, which was verified to be caused by a mutation in hepatocyte nuclear factor 1α gene (c.598C>T, p.Arg200Trp). In addition, the patient had a neuroendocrine tumor simultaneously, and a KMT2D gene mutation (c.5587C>G, p.Pro1863Ala) might be associated with this leson.

4-Diazoisochroman-3-imines: A Class of Metal Carbene Precursors for the Synthesis of Isochromene Derivatives.

4-Diazoisochroman-3-imines were investigated for their synthetic applications as a new class of metal carbene precursors. Under the catalysis from a Rh(II) complex, this class of α-diazo imidates reacted with alkenes and conjugated dienes through a formal [2 + 1] (i.e., cyclopropanation) or [4 + 3] cycloaddition to furnish spiro[cyclopropane-1,4'-isochroman]-3'-imines and tetrahydroisochromeno[3,4-b] azepines, respectively. When Rh(II)/AgOTf was used as cocatalyst, the formal [3 + 2] cycloaddition of 4-diazoisochroman-3-imines with terminal alkynes took place, leading to the synthesis of 2-aryl-3,5-dihydroisochromeno[3,4-b]pyrroles.

TfOH-Catalyzed Reaction between 3-Diazoindolin-2-imines and Electron-Rich Arenes: Access to 3-Aryl-2-aminoindoles.

TfOH-catalyzed reactions between 3-diazoindolin-2-imines and electron-rich arenes were disclosed. These metal-free reactions furnished 3-aryl-2-aminoindoles in moderate to excellent yields with the tolerance of a broad range of functional groups.

Effect of hydrophilic additives on the dissolution and pharmacokinetic properties of itraconazole-enteric polymer hot-melt extruded amorphous solid dispersions.

Hot-melt extrusion technology has been widely reported for producing amorphous solid dispersions of poorly water-soluble compounds. A number of studies revealed that enteric polymers containing ionizable groups are able to improve the physical stability and maintain drug supersaturation, thereby enhancing oral bioavailability. However, our previous studies found that itraconazole (ITZ)-enteric polymer amorphous solid dispersions are hydrophobic and poorly wettable. Moreover, drug release in an acidic environment (i.e. stomach) is very limited, indicating a narrow absorption window. In the present study, we investigated the effect of hydrophilic additives on the in vitro and in vivo performance of ITZ-enteric polymer amorphous solid dispersions. Incorporating Vitamin E TPGS into ITZ-HPMCAS amorphous solid dispersions significantly improved drug release in the acidic media. Surprisingly, a low concentration of Vitamin E TPGS also enhanced the degree of drug supersaturation in neutral pH media, which is unique as compared with other tested hydrophilic additives. This effect is not due to the solubilization of the surfactant. We further formulated the amorphous solid dispersions into tablet dosage forms and evaluated their performance in a bio-relevant dissolution media. Our optimized formulations exhibited drastically enhanced dissolution profiles as compared with the commercial ITZ product and ITZ amorphous solid dispersion without hydrophilic additive. In vivo study showed that Vitamin E TPGS induced rapid drug absorption after oral administration. Moreover, the elimination half-life of ITZ was prolonged due to the enzyme inhibition effect of Vitamin E TPGS.

Dissolution enhancement of itraconazole by hot-melt extrusion alone and the combination of hot-melt extrusion and rapid freezing--effect of formulation and processing variables.

We investigated the effects of the hot-melt extrusion (HME) process on the properties of itraconazole (ITZ) amorphous solid dispersions made by thin film freezing (TFF) technology. The ITZ-HPMCAS L (1:2) TFF composition exhibited limited drug release in acidic media. HME of the ITZ-HPMCAS TFF composition with hydrophilic carriers improved the drug release rate in acidic media. The type and level of hydrophilic carrier in the composition affected the dissolution profiles of the extrudates. A design of experiments (DoE) study was conducted to elucidate those effects. Hot-melt extrusion processing variables such as extrusion temperature and screw configuration also played a critical role on the properties of the extruded compositions. A higher degree of mixing reduced the crystallinity of semicrystalline excipients and favored the drug release in the acidic media; moreover, the drug precipitation rate in the neutral pH media was reduced.

Hot-melt extrusion--basic principles and pharmaceutical applications.

Originally adapted from the plastics industry, the use of hot-melt extrusion has gained favor in drug delivery applications both in academia and the pharmaceutical industry. Several commercial products made by hot-melt extrusion have been approved by the FDA, demonstrating its commercial feasibility for pharmaceutical processing. A significant number of research articles have reported on advances made regarding the pharmaceutical applications of the hot-melt extrusion processing; however, only limited articles have been focused on general principles regarding formulation and process development. This review provides an in-depth analysis and discussion of the formulation and processing aspects of hot-melt extrusion. The impact of physicochemical properties of drug substances and excipients on formulation development using a hot-melt extrusion process is discussed from a material science point of view. Hot-melt extrusion process development, scale-up, and the interplay of formulation and process attributes are also discussed. Finally, recent applications of hot-melt extrusion to a variety of dosage forms and drug substances have also been addressed.

Trichoderma harzianum Cellulase Gene thph2 Affects Trichoderma Root Colonization and Induces Resistance to Southern Leaf Blight in Maize.

Trichoderma, widely distributed all over the world, is commonly found in soil and root ecosystems. It is a group comprising beneficial fungi that improve plant disease resistance and promote plant growth. Studies have shown that Trichoderma cellulases can also improve plant disease resistance. Based on previous studies, we reported that a C6 zinc finger protein (Thc6) regulates two cellulase genes, thph1 and thph2, to induce ISR responses in plants. Therefore, in this study, we focused on the role of thph2 in the colonization of maize roots by T. harzianum and the induction of systemic resistance against southern leaf blight. The results showed that thph2 had a positive regulatory effect on the Trichoderma colonization of maize roots. After the root was treated with Trichoderma, the leaf defense genes AOS, LOX5, HPL, and OPR1 were expressed to resist the attack of Cochliobolus heterostrophus. The pure Thph2 protein also resulted in a similar induction activity of the AOS, LOX5, HPL, and OPR1 expression in maize roots, further demonstrating that thph2 can induce plant defense responses and that signal transduction occurs mainly through the JA signaling pathway.

Preparation of High Water-Soluble Trichoderma Co-Culture Metabolite Powder and Its Effects on Seedling Emergence Rate and Growth of Crops.

Trichoderma spp. are widely used beneficial microbes in agricultural production; however, the improper carrier choice for Trichoderma agent preparation can alter the effectiveness of Trichoderma fungicides. In this study, the co-culture of four Trichoderma strains produced a large amount of free amino acids, with a content of 392.8414 ug/mL, and significantly improved the production level of γ-aminobutyric acid. A greenhouse experiment further showed that the co-culture of Trichoderma synergistically improved the female flower development and bacterial angular leaf spot resistance. The effects of ten kinds of carriers were compared in terms of water absorption and heat generation, as well as their effects on the seedling emergence rate and the plant growth promotion of maize, cucumber, and pakchoi cabbage. Each carrier was screened to mix with four strains of co-culture metabolites to prepare highly soluble and quality powders. The results showed that there were different effects of the carriers themselves and Trichoderma strain co-culture metabolite powder prepared with the carriers on seedling emergence rate and seedling growth. Β-cyclodextrin performed best in high solubility and low heat generation upon absorbing water and in easy drying in processing operations. Trichoderma strains co-culture metabolite powder with ß-cyclodextrin as a carrier provided the most obvious promotion effects on seedling emergence rate and seedling growth. Therefore, ß-cyclodextrin was determined to be an ideal carrier to prepare a highly water-soluble Trichoderma agent. Taken together, the study successfully developed a new type of highly soluble powder containing Trichoderma co-culture metabolites that is expected to benefit farming drip irrigation and spraying systems for the promotion of crop growth and disease control.

[A case control study:the treatment of cervical vertigo with micro needle knife].

OBJECTIVE: To observe the clinical efficacy of micro needle knife therapy on cervical vertigo. METHODS: A total of 300 patients with cervical vertigo treated from January 1, 2017 to December 31, 2019 were randomly divided into micro needle knife group (96 cases, 4 cases falling off), traditional acupuncture group (96 cases, 4 cases falling off) and oral drug group(95 cases, 5 cases falling off). The micro needle knife group was treated with micro needle knife in the local upper cervical segment once every other day for 7 times; the traditional acupuncture group was treated with traditional acupuncture once a day for 2 weeks;the oral drug group was given Merislon (betahistine mesilate tablets) orally, 6 mg each time, 3 times a day for 2 weeks. The patients were followed up before treatment, at the end of treatment and 3 months after treatment. The dizziness handicap inventory(DHI) was observed and the curative effect was evaluated according to the DHI score. RESULTS: At the end of the course of treatment and 3 months after the treatment, DHI scores of the three groups were significantly lower than those before treatment(P<0.01), and the DHI scores of micro needle knife group were lower than those of traditional acupuncture group and oral drug group at the same time point after treatment (P<0.01). There was no statistically significant difference in DHI scores between traditional acupuncture group and oral drug group at the same time after treatment(P< 0.05). The curative effect was evaluated according to DHI score:in micro needle knife group, 50 cases were cured, 28 cases were markedly effective, 14 cases were improved, the total effective rate was 95.83%; in traditional acupuncture group, 28 cases were cured, 26 cases were markedly effective, and 24 cases were improved, with the total effective rate of 81.25%;in oral drug group, 18 cases were cured, 20 cases were markedly effective, and 28 cases were improved, with the total effective rate of 69.47%. The total effective rate of micro needle knife group was significantly higher than that of other two groups (χ2=45.956, P=0.000). Among the cured patients in the three groups, the time required in the micro needle knife group was significantly less than that in the traditional acupuncture group and oral drug group(F=18.796, P=0.000). CONCLUSION: Micro needle knife loosening atlantoaxial soft tissue has obvious curative effect on cervical vertigo which clinical cure rate, effective rate and treatment time required for cured patients are better than traditional acupuncture and oral drug.

[Micro-needle knife in treatment of cervical vertigo and its effect on vertebral artery hemodynamics].

OBJECTIVE: To compare the effect of micro-needle knife therapy and betahistine mesilate tablets in the treatment of cervical vertigo (CV) and the influence on the mean blood flow velocity (Vm) of vertebral artery. METHODS: A total of 200 patients with CV were randomly divided into a micro-needle knife group (100 cases, 5 cases dropped off) and a medication group (100 cases, 3 cases dropped off). In the micro-needle knife group, micro-needle knife was performed on the suboccipital triangle of the atlantoaxial segment of the posterior neck, once every other day, for a total of 7-time treatment. The medication group received oral betahistine mesilate tablets, 6 mg each time, three times a day, for 14 consecutive days. The dizziness handicap inventory (DHI) scores of the two groups were observed before treatment, after treatment and during follow-up 3 months after treatment; the Vm of vertebral artery was compared between the two groups before and after treatment, and the clinical effect was evaluated during follow-up. RESULTS: After treatment and during follow-up, the DHI scores of the two groups were lower than those before treatment (P<0.001), and those in the micro-needle knife group were lower than the medication group (P<0.001). After treatment, the Vm of bilateral vertebral arteries in both groups was higher than that before treatment (P<0.05), and that in the micro-needle knife group was higher than the medication group (P<0.05). The total effective rate of the micro-needle knife group was 96.8% (92/95), which was higher than 67.0% (65/97) of the medication group (P<0.001). CONCLUSION: Micro-needle knife therapy can improve vertigo symptoms and balance dysfunction, increase the mean blood flow velocity of vertebral artery in CV patients, and its clinical efficacy is better than oral betahistine mesilate tablets.

Curvularia lunata and Curvularia Leaf Spot of Maize in China.

Curvularia leaf spot (CLS), primarily caused by Curvularia lunata (Wakker) Boedijn (C. lunata), is widely distributed in maize production regions in China. It occurs in all the developmental stages of maize and causes economic losses. The epidemic and yield loss estimation models have been constructed for the disease. C. lunata has obvious virulence differentiation and produces multiple virulence factors. CLS is managed by application of chemical and biological agents and by quantitative resistance conferred by 5 to 6 quantitative trait loci (QTL). This review summarizes research on the understanding of CLS biological characteristics, virulence factors of C. lunata, host resistance genetics, and disease management strategies in China.

miR-503/Apelin-12 mediates high glucose-induced microvascular endothelial cells injury via JNK and p38MAPK signaling pathway.

INTRODUCTION: Diabetic patients are often accompanied by complications of diabetic vascular disease, which could lead to heart failure or stroke. In this work, we explored the role of miR-503/Apelin-12 in diabetic angiopathy (DA) in vitro. METHODS: ELISA and qPCR were applied to assess the expression of miR-503 and Apelin-12 in high glucose (HG)-treated microvascular endothelial cells (HMEC-1). The effects of miR-503 on apoptosis, inflammation and oxidative stress were assessed by flow cytometry, western blotting, qPCR, and ELISA. The interaction between miR-503 and Apelin-12 was evaluated by dual-luciferase reporter assay, qPCR and ELISA, respectively. Western blotting was performed to examine the function of miR-503/Apelin-12 on JNK and p38MAPK activation. RESULTS: MiR-503 was markedly increased and Apelin-12 was decreased in HG-treated HMEC-1 cells. MiR-503 inhibitor significantly assuaged apoptosis, inflammation and oxidative stress in HMEC-1 cells. MiR-503 could specifically bind to the 3'UTR of Apelin and inversely downregulate Apelin-12 expression. Furthermore, Apelin-12 suppressed apoptosis, inflammation and oxidative stress. Inhibition of Apelin-12 could partially reverse the decrease of p-JNK and p-p38 expression levels induced by miR-503 suppression. CONCLUSION: In HG-induced microvascular cells injury, miR-503/Apelin-12 enhances inflammation and oxidative stress by regulating JNK and p38MAPK pathway, suggesting a potential therapeutic target for DA.

Arthrobacter halodurans sp. nov., a new halotolerant bacterium isolated from sea water.

A novel Gram-positive, halotolerant, non-sporulating, non-motile, catalase-positive, oxidase-negative and aerobic bacterium, designated strain JSM 078085(T), was isolated from sea water collected from the South China Sea. Strain JSM 078085(T) exhibited a rod-coccus growth cycle and produced a yellow pigment. The strain was able to grow in the presence of 0-12% (w/v) NaCl and at pH 6.0-9.5 and 4-35 degrees C; optimum growth was observed at pH 7.0 and 25-30 degrees C in the absence of NaCl. The peptidoglycan type was A4alpha (L: -Lys-L: -Ala-L: -Glu). Cell-wall sugars contained galactose and glucose. Strain JSM 078085(T) contained menaquinone MK-9(H(2)) as the major respiratory quinone and diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol as the major polar lipids. The major cellular fatty acids were anteiso-C(15:0), iso-C(15:0) and anteiso-C(17:0) and the DNA G + C content was 63.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that strain JSM 078085(T) should be assigned to the genus Arthrobacter, being most closely related to the type strain of Arthrobacter rhombi (sequence similarity 97.1%), and the two strains formed a distinct lineage in the phylogenetic tree. The level of DNA-DNA relatedness between strain JSM 078085(T) and the type strain of Arthrobacter rhombi was 10.6%. The combination of phylogenetic analysis, DNA-DNA relatedness, phenotypic characteristics and chemotaxonomic data supported the view that strain JSM 078085(T) represents a novel species of the genus Arthrobacter, for which the name Arthrobacter halodurans sp. nov. is proposed. The type strain is JSM 078085(T) (=DSM 21081(T)=KCTC 19430(T)).

[Case-control study on the treatment of heel spur syndrome with modified stretching manipulation combined with needle Dao loosing].

OBJECTIVE: To study the clinical effects of modified plantar fascia stretching manipulation combined with needle Dao loosing in the treatment of heel spur syndrome. METHODS: From September 2010 to September 2015, 115 patients diagnosed as heel spur syndrome were divided into two groups: treatment group and control group. There were 58 patients in the treatment group, including 21 males and 37 females, ranging in age from 26 to 73 years old, with the course of disease from 6 to 51 months. The patients in the treatment group were treated with modified plantar fascia stretching manipulation combined with needle Dao loosing. There were 57 patients in the control group, including 22 males and 35 females, ranging in age from 31 to 75 years old, with the course of disease from 7 to 58 months. The patients in the control group were treated with traditonal stretching manipulation combined with needle Dao loosing. The NRS scores of heel pain were evaluated at the 1st week, 1 and 3 months after treatment; and the clinical effects of the two groups were evaluated with the Foot and Ankle Ability Measure(FAAM) scale evaluation system. RESULTS: The numerical rating scale(NRS) scores were 3.89±0.96 and 2.46±0.95 in the treatment group 1 month and 3 months after treatment, which were superior to 4.52±1.21 and 4.73±1.11 in the control group; and the FAAM rates in the treatment group were (3.89±0.96)% and(2.46±0.95)% separately 1 month and 3 months after treatment, which were better than (4.52±1.21)% and (4.73±1.11)% in the control group. The total curative effects of the treatment group were better than that of the control group. CONCLUSIONS: The modified plantar fascia stretching manipulation combined with needle Dao loosing can locate the traction point, which has a significant effect on the patients with heel spur syndrome. Compared with traditonal stretching manipulation combined with needle Dao loosing, this modified mainpulation combined with needle knife loosing has better medium to-long term effects.

Rhodium-Catalyzed Cycloadditions between 3-Diazoindolin-2-imines and 1,3-Dienes.

Azepino[2,3-b]indoles were regioselectively prepared through rhodium-catalyzed formal aza-[4 + 3] cycloaddition between 3-diazoindolin-2-imines and 1,3-dienes in moderate to good yields. Using 2-[(trimethylsilyl)oxy]-1,3-butadiene as the diene component, azepino[2,3-b]indol-4(1H)-ones were constructed. Furthermore, the reactions of cyclic dienes, such as 1,3-cyclohexadiene and 1,3-cyclopentadiene, furnished the corresponding [3 + 2] cycloaddition products.

Query-Adaptive Hash Code Ranking for Large-Scale Multi-View Visual Search.

Hash-based nearest neighbor search has become attractive in many applications. However, the quantization in hashing usually degenerates the discriminative power when using Hamming distance ranking. Besides, for large-scale visual search, existing hashing methods cannot directly support the efficient search over the data with multiple sources, and while the literature has shown that adaptively incorporating complementary information from diverse sources or views can significantly boost the search performance. To address the problems, this paper proposes a novel and generic approach to building multiple hash tables with multiple views and generating fine-grained ranking results at bitwise and tablewise levels. For each hash table, a query-adaptive bitwise weighting is introduced to alleviate the quantization loss by simultaneously exploiting the quality of hash functions and their complement for nearest neighbor search. From the tablewise aspect, multiple hash tables are built for different data views as a joint index, over which a query-specific rank fusion is proposed to rerank all results from the bitwise ranking by diffusing in a graph. Comprehensive experiments on image search over three well-known benchmarks show that the proposed method achieves up to 17.11% and 20.28% performance gains on single and multiple table search over the state-of-the-art methods.

Structure Sensitive Hashing With Adaptive Product Quantization.

Hashing has been proved as an attractive solution to approximate nearest neighbor search, owing to its theoretical guarantee and computational efficiency. Though most of prior hashing algorithms can achieve low memory and computation consumption by pursuing compact hash codes, however, they are still far beyond the capability of learning discriminative hash functions from the data with complex inherent structure among them. To address this issue, in this paper, we propose a structure sensitive hashing based on cluster prototypes, which explicitly exploits both global and local structures. An alternating optimization algorithm, respectively, minimizing the quantization loss and spectral embedding loss, is presented to simultaneously discover the cluster prototypes for each hash function, and optimally assign unique binary codes to them satisfying the affinity alignment between them. For hash codes of a desired length, an adaptive bit assignment is further appended to the product quantization of the subspaces, approximating the Hamming distances and meanwhile balancing the variance among hash functions. Experimental results on four large-scale benchmarks CIFAR-10, NUS-WIDE, SIFT1M, and GIST1M demonstrate that our approach significantly outperforms state-of-the-art hashing methods in terms of semantic and metric neighbor search.