Search

Inhibition of angiotensin-I converting enzyme (ACE) is an important means of treating hypertension since it plays an important regulatory function in the renin-angiotensin system. The aim of this study was to investigate the ACE inhibitory effect of bioactive peptides from green coffee beans using in silico and in vitro methods. Alcalase and thermolysin were employed to hydrolyze protein extract from coffee beans. Bioactive peptides were identified by LC-MS/MS analysis coupled with database searching. The potential bioactivities of peptides were predicted by in silico screening, among which five novel peptides may have ACE inhibitory activity. In vitro assay was carried out to determine the ACE inhibitory degree. Two peptides (IIPNEVY, ITPPVMLPP) were obtained with IC50 values of 57.54 and 40.37 μM, respectively. Furthermore, it was found that two inhibitors bound to the receptor protein on similar sites near the S1 active pocket of ACE to form stable enzyme–peptide complexes through molecular docking, and the Lineweaver–Burk plot showed that IIPNEVY was a noncompetitive inhibitor, and ITPPVMLPP was suggested to be a mixed-type inhibitor. Our study demonstrated that two peptides isolated from coffee have potential applications as antihypertensive agents.

The expression level of retinol‐binding protein 4 (RBP4) protein is closely related to liver damage and plays an important role in the diagnosis and prognosis of cancer. However, the preparation of anti‐RBP4 mAb or exploration on the application of anti‐RBP4 mAb has not been reported thus far. In the present study, we constructed a pET30a‐RBP4 recombinant vector, used E. coli BL21 (DE3) as the vector to express the RBP4 recombinant protein and prepared anti‐RBP4 mAb using hybridoma technology. We performed immunohistochemical analysis on hepatocellular carcinoma (HCC) and adjacent tissues by using this anti‐RBP4 mAb. In addition to the high‐purity RBP4 recombinant protein, we successfully developed the anti‐RBP4 mAb with high affinity and specificity; it binds to natural RBP4 protein and is suitable for immunohistochemical analysis.

In this letter, high-performance Al2O3/ $\beta$ -Ga2O3 (001) metal-insulator-semiconductor (MIS) capacitor has been demonstrated. The capacitance-voltage (C–V) curves of the Al2O3/ $\beta$ -Ga2O3 (001) MIS capacitor remain stable under different measurement frequencies. The leakage current density is lower than $2.0 \times 10^{-8}$ A/cm2 when the gate voltage is in the range of −5~13 V. The fixed charge and trapped charge densities in Al2O3 film are $4.4 \times 10^{12}$ and $6.0 \times 10^{11}$ cm−2, respectively. Average and minimum interface trapped charge density ( ${\mathrm {D}}_{it}$ ) for Al2O3/ $\beta$ -Ga2O3 (001) interface has been extracted to be as low as $3.3 \times 10^{11}$ and $2.3 \times 10^{11}$ cm−2 eV−1 via the Terman method, respectively. The low ${\mathrm {D}}_{it}$ is probably attributed to the modification of vacancy defects and the introduction of hydroxyl groups at the Al2O3/ $\beta$ -Ga2O3 (001) interface after piranha solution pretreatment for $\beta$ -Ga2O3.

Microtubules play an important role in the process of cell mitosis and can form a spindle in the mitotic prophase of the cell, which can pull chromosomes to the ends of the cell and then divide into two daughter cells to complete the process of mitosis. Tubulin inhibitors suppress cell proliferation by inhibiting microtubule dynamics and disrupting microtubule homeostasis. Thereby inducing a cell cycle arrest at the G2/M phase and interfering with the mitotic process. It has been found that a variety of chalcone derivatives can bind to microtubule proteins and disrupt the dynamic balance of microtubules, inhibit the proliferation of tumour cells, and exert anti-tumour effects. Consequently, a great number of studies have been conducted on chalcone derivatives targeting microtubule proteins. In this review, synthetic or natural chalcone microtubule inhibitors in recent years are described, along with their structure-activity relationship (SAR) for anticancer activity.

Abstract Although functional and structural abnormalities in brain regions involved in the neurobiology of fear and anxiety have been observed in patients with social anxiety disorder (SAD), the findings have been heterogeneous due to small sample sizes, demographic confounders, and methodological differences. Besides, multimodal neuroimaging studies on structural-functional deficits and couplings are rather scarce. Herein, we aimed to explore functional network anomalies in brain regions with structural deficits and the effects of structure-function couplings on the SAD diagnosis. High-resolution structural magnetic resonance imaging (MRI) and resting-state functional MRI images were obtained from 49 non-comorbid patients with SAD and 53 demography-matched healthy controls. Whole-brain voxel-based morphometry analysis was conducted to investigate structural alterations, which were subsequently used as seeds for the resting-state functional connectivity analysis. In addition, correlation and mediation analyses were performed to probe the potential roles of structural-functional deficits in SAD diagnosis. SAD patients had significant gray matter volume reductions in the bilateral putamen, right thalamus, and left parahippocampus. Besides, patients with SAD demonstrated widespread resting-state dysconnectivity in cortico-striato-thalamo-cerebellar circuitry. Moreover, dysconnectivity of the putamen with the cerebellum and the right thalamus with the middle temporal gyrus/supplementary motor area partially mediated the effects of putamen/thalamus atrophy on the SAD diagnosis. Our findings provide preliminary evidence for the involvement of structural and functional deficits in cortico-striato-thalamo-cerebellar circuitry in SAD, and may contribute to clarifying the underlying mechanisms of structure-function couplings for SAD. Therefore, they could offer insights into the neurobiological substrates of SAD.

Abstract Background tRNA-derived fragments (tRFs) have been shown to have critical regulatory roles in cancer biology. However, the contributions of tRFs to colorectal cancer (CRC) remain largely unknown. Methods tRF3008A (a tRFRNA derived from tRNAVal) was identified by RNA sequencing and validated by quantitative reverse transcription PCR. The role of tRF3008A in CRC progression was assessed both in vitro and in vivo, and its downstream target genes were identified and validated in CRC cells. RNA pull-down with mass spectrometry and AGO-RIP were used to confirm the interaction of tRF3008A and AGO proteins. The clinical implications of tRF3008A were assessed in CRC tissues and blood samples. Results The expression of tRF3008A was reduced in colorectal cancer, and its reduction was significantly correlated with advanced and metastatic disease in CRC. Patients with low tRF3008A expression showed significantly shorter DFS, and multivariate analysis identified tRF3008A as an independent prognostic biomarker in CRC. Functionally, tRF3008A inhibits the proliferation and migration of CRC in vivo and in vitro by repressing endogenous FOXK1, a positive regulator of the Wnt/β-catenin pathway. Mechanistically, tRF3008A binds to AGO proteins as a guide to destabilize oncogenic FOXK1 transcript. Conclusions tRF3008A suppresses the metastasis and progression of colorectal cancer by destabilizing FOXK1 in an AGO-dependent manner.

It is generally accepted herbal polysaccharide and is a bioactive compound of herbal medicines with immunomodulatory activities. It has a wide range of pharmacological effects. It can be used as a green substitute for antibiotics or as a feed additive in quail breeding. Therefore, the herbal polysaccharide has a broader and safer application prospect. The immunosuppressive disease of quail is one of the most important infectious diseases. It seriously affects the growth, development, and production performance of quail, causing huge economic losses to quail industry. However, there is no report on the effective alleviation of spleen injury in immunosuppressed animals by herbal polysaccharide. Therefore, we established a pathological model of immunosuppressive Chinese yellow quail for the first time, with the Terminalia chebula Retz polysaccharide (TCP) as the control, and histological observation, TUNEL staining were used to study the effects of Rubia cordifolia L. processed Terminalia chebula Retz polysaccharide (RTCP) on splenic tissue structure and apoptosis of immunosuppressed Chinese yellow quail. The experimental results showed that spleen organ index of the cyclophosphamide (CTX) group was significantly lower than these of blank control group, the TCP group and the RTCP group (P < 0.05). And the number of splenic nodules in the CTX group was significantly lower than that in the blank control group (P < 0.01). Compared with the CTX group, the spleen volume of the TCP group and the RTCP group increased, and the number and area of spleen nodules increased. Among them, the spleen nodules in the RTCP group were significantly more higher than that in the CTX group (P < 0.01). Meanwhile, TUNEL staining showed that the TUNEL positive cells in the CTX group were the most significantly higher than those in the blank control group (P < 0.01). TCP group and RTCP group were significantly higher than the blank control group (P < 0.01), but significantly lower than CTX group (P < 0.05). All these results suggested that RTCP could effectively improve CTX-induced spleen damage in immunosuppressed Chinese yellow quails by promoting the recovery of spleen organ index, repairing the spleen tissue structure, and diminishing the apoptosis. Moreover, RTCP is more effective than TCP. The results prove that the efficacy of RTCP in protecting spleen from CTX induced injury was enhanced after processing with Rubia cordifolia L. Therefore, our findings will provide more possibilities to promote the clinical application and development of processed traditional Chinese medicine in the further.

Purpose. Few related factors of low bone mass in Cushing’s disease (CD) have been identified so far, and relevant sufficient powered studies in CD patients are rare. On account of the scarcity of data, we performed a well-powered study to identify related factors associated with low bone mass in young CD patients. Methods. This retrospective study included 153 CD patients (33 males and 120 females, under the age of 50 for men and premenopausal women). Bone mineral density (BMD) of the left hip and lumbar spine was measured by dual energy X-ray absorptiometry (DEXA). In this study, low bone mass was defined when the Z score was −2.0 or lower. Results. Among those CD patients, low bone mass occurred in 74 patients (48.37%). Compared to patients with normal BMD, those patients with low bone mass had a higher level of serum cortisol at midnight (22.31 (17.95-29.62) vs. 17.80 (13.75-22.77), p=0.0006), testosterone in women (2.10 (1.33–2.89) vs. 1.54 (0.97–2.05), p=0.0012), higher portion of male (32.43% vs. 11.54%, p=0.0016) as well as hypertension (76.12% vs. 51.67%, p=0.0075), and lower IGF-1 index (0.59 (0.43–0.76) vs. 0.79 (0.60–1.02), p=0.0001). The Z score was positively associated with the IGF-1 index in both the lumbar spine (r = 0.35153, p

Patients bearing liver metastasis of pancreatic adeno carcinoma (PDAC) suffer from poor prognosis due to its short duration and high mortality. Complex tumor microenvironment (TME) exists in liver metastatic niches, and tumor-associated macrophages (TAMs) have play vital roles in metastasis generation and outgrowth. We have discovered that M2 type TAM-derived SEMA5A could bind to its tumor cell-expressed receptor PLXNB3 to promote tumor cell proliferation and outgrowth. We utilized liver metastasis samples of PDAC patients, intrasplenic injection mouse models, and KrasG12D/Trp53R172H/Pdx1-Cre (KPC) mouse models for in vivo study. In mechanism investigation, we have discovered that SEMA5A-PLXNB3 axis could achieve tumor cell proliferation and survival via enhancing aerobic glycolysis termed as the Warburg effects. Targeting this axis may be a potential therapeutic approach for PDAC patients with unresectable liver metastasis.

ObjectiveTo investigate the association between anemia and progression of diabetic kidney disease (DKD) in type 2 diabetes.MethodsThis was a retrospective study. A total of 2570 in-patients with type 2 diabetes hospitalized in Jinan branch of Huashan hospital from January 2013 to October 2017 were included, among whom 526 patients were hospitalized ≥ 2 times with a median follow-up period of 2.75 years. Annual rate of eGFR decline was calculated in patients with multiple admissions. A rate of eGFR decline exceeding -5 ml/min per 1.73 m2 per year was defined as rapid eGFR decline. The prevalence of DKD and clinical characteristics were compared between anemia and non-anemia patients. Correlation analysis was conducted between anemia and clinical parameters. Comparison of clinical features were carried out between rapid eGFR decline and slow eGFR decline groups. The risk factors for rapid DKD progression were analyzed using logistic regression analysis.ResultsThe prevalence of anemia was 28.2% among the 2570 diabetic patients, while in patients with DKD, the incidence of anemia was 37.8%. Patients with anemia had greater prevalence of DKD, higher levels of urinary albumin-to-creatinine ratio (UACR), serum creatinine, BUN, urine α1-MG, urine β2-MG, urine NAG/Cr, hsCRP, Cystatin C, homocysteine and lower eGFR, as compared to the patients without anemia. Anemia was correlated with age, UACR, eGFR, urinary NAG/Cr, hsCRP and diabetic retinopathy (DR). Logistic regression analysis of 526 patients with type 2 diabetes during the follow-up period showed that anemia was an independent risk factor for rapid eGFR decline.ConclusionAnemia is associated with worse renal function and is an independent risk factor for rapid eGFR decline in type 2 diabetes.

In recent years, with the development of new energy technology and the country’s strong support for electric vehicles, there is a lack of effective electric vehicle charging fault analysis and diagnosis methods at this stage. A comprehensive analysis of the working principle of the charging process of electric vehicles, based on the clarification of the failure mechanism of the power battery and charging equipment, analyzes the fault-related factors affecting the power battery and charging equipment from multiple angles, and summarizes the relationship between the power battery and charging equipment. The feature parameters related to equipment failure are discretized by the k-means clustering algorithm. Using the optimized FP-Growth algorithm based on weights, the association rules between the power battery and charging equipment failures and the characteristic parameters of the failure factors are mined, and the correlation of the failures is analyzed based on the association rules, and the correlation between the failure factors and the failures is obtained relevant level.

Pancreatic cystic neoplasms (PCNs) are a group of heterogeneous diseases with distinct prognosis. Existing differential diagnosis methods require invasive biopsy or prolonged monitoring. We sought to develop an inexpensive, non-invasive differential diagnosis system for PCNs based on radiomics features and clinical characteristics for a higher total PCN screening rate. We retrospectively analyzed computed tomography images and clinical data from 129 patients with PCN, including 47 patients with intraductal papillary mucinous neoplasms (IPMNs), 49 patients with serous cystadenomas (SCNs), and 33 patients with mucinous cystic neoplasms (MCNs). Six clinical characteristics and 944 radiomics features were tested, and nine features were finally selected for model construction using DXScore algorithm. A five-fold cross-validation algorithm and a test group were applied to verify the results. In the five-fold cross-validation section, the AUC value of our model was 0.8687, and the total accuracy rate was 74.23%, wherein the accuracy rates of IPMNs, SCNs, and MCNs were 74.26%, 78.37%, and 68.00%, respectively. In the test group, the AUC value was 0.8462 and the total accuracy rate was 73.61%. In conclusion, our research constructed an end-to-end powerful PCN differential diagnosis system based on radiomics method, which could assist decision-making in clinical practice.

Aiming at the difficulties of few real samples for defective insulators and complex background of aerial images, this paper proposes a detection method based on target search and cascade recognition. Using the SINet framework, we apply fine-grained texture enhancement to different sizes of receptive fields. Through nearest-neighbor decoding and grouping reverse attention, the more recognizable features are guided to aggregate and generate a refined location area map by performing cascading purification operations. Additionally, we integrate the classification network to complete the solution. Experimental results show that the AUC value is up to 99.82%, which demonstrates the effectiveness and superiority of the proposed method on insulator defect detection.

Aiming at the problem that the detection and damage recognition algorithm of insulator aerial images is difficult to be applied to the embedded platform, this paper proposed an improved Tiny-YOLOv4 lightweight target detection network algorithm. This algorithm combined the Self-Attention mechanism and ECA-Net (Efficient Channel Attention Neural Networks), which could greatly reduce the complexity of the original YOLOv4 algorithm, and the model size is 24.9 MB. Under the condition of ensuring the detection accuracy (>91%), the detection speed is as high as 94FPS. It is transplanted to the Jetson Xavier NX embedded platform, and the average detection speed reaches 22FPS, which effectively meets the real-time detection requirements in the power inspection.

To realize the accurate identification and segmentation of the insulator string in the complex background image with diverse appearance and obscuration, this paper proposes an insulator segmentation method based on improved U-Net. The algorithm embeds the attention mechanism ECA-Net (Efficient Channel Attention Neural Networks) in the coding stage of U-Net to improve the model’s ability to extract semantic features, thereby improving the accuracy of insulator detection. Experimental results show that the average overlap IOU of the proposed method is 96.8%, which can more accurately segment different types of insulators in complex backgrounds.

Abstract Background Never in mitosis gene-A (NIMA)-related expressed kinase 2 (NEK2) is a serine/threonine protein kinase regulated by the cell cycle. The purpose of this study was to obtain NEK2 protein to prepare an anti-NEK2 monoclonal antibody (mAb) and explore the application of the anti-NEK2 mAb of therapeutic and diagnostic in hepatocellular carcinoma (HCC). Results The NEK2 gene sequence was cloned from the normal liver cell line HL7702, and the full-length NEK2 gene sequence was cloned into the prokaryotic expression vector pET30a and transformed into Escherichia coli BL21 (DE3) cells. The recombinant fusion protein was obtained under optimized conditions and injected in BALB/c mice to prepare an anti-NEK2 mAb. By screening, we obtained a stable hybridoma cell line named 3A3 that could stably secrete anti-NEK2 mAb. Anti-NEK2 3A3 mAb was purified from ascites fluid. The isotype was IgG1, and the affinity constant (Kaff) was 6.0 × 108 L/mol. Western blot, indirect enzyme-linked immunosorbent assay (iELISA), immunofluorescence and immunocytochemical analyses showed that the mAb could specifically recognize the NEK2 protein. MTT assays showed that the mAb 3A3 could inhibit the proliferation of HCC cells. KEGG pathway analysis showed that NEK2 might affected pathways of the cell cycle. Moreover, NEK2-related genes were mainly enriched in the S and G2 phases and might act as tumor-promoting genes by regulating the S/G2 phase transition of HCC cells. Conclusions An anti-NEK2 mAb with high potency, high affinity and high specificity was prepared by prokaryotic expression system in this study and may be used in the establishment of ELISA detection kits and targeted treatment of liver cancer.

Objective To investigate the MRI features and clinical outcomes of unexpected uterine sarcomas in patients after high-intensity focused ultrasound (HIFU) ablation for presumed uterine fibroids. Materials and methods 15,759 consecutive patients who came for HIFU treatment, from November 2008 to September 2019, for presumed uterine fibroids were retrospectively reviewed. All the patients had completed a pre-HIFU MRI. All MRI images were independently analyzed and interpreted by two radiologists in every center. Results According to the T2WI MRI features of hyperintensity, accompanied by irregular margins, necrosis or cystic degeneration, multi-lobulated lesion with internal septation, 46 patients were suspected to be uterine sarcomas before HIFU. Eleven patients were histologically diagnosed as uterine sarcomas after laparotomy. Among the 15713 patients who received HIFU treatment for presumed uterine fibroids, 8 patients were found to have occult recurrence during the follow-up period, and 6 were confirmed histologically as uterine sarcomas after laparotomy. The incidence rate of uterine sarcomas was 0.108% (17/15759). Among them, 12 cases were low-grade endometrial stromal sarcoma (LG-ESS) and 5 cases were uterine leiomyosarcoma (LMS). No histological dissemination of the sarcoma was detected in patients with unexpected uterine sarcomas. Conclusion Although some MRI features of uterine sarcomas and uterine fibroids overlapped, MRI is valuable in distinguishing between uterine fibroids and uterine sarcomas. HIFU does not seem to cause histological dissemination of the sarcoma, but follow-up visits should be strictly adhered to in order to detect unexpected uterine sarcomas at an early stage and to treat them in a timely manner.

Abstract Background Acoustic cavitation plays an important role in the medical treatment using high-intensity focused ultrasound (HIFU), but unnecessarily strong cavitation also could deform the morphology and enlarge the size of lesions. It is known that the increase of ambient hydrostatic pressure (P stat) can control the acoustic cavitation. But the question of how the decrease of P stat and dissolved oxygen concentration (DOC) influence the strength of cavitation has not been thoroughly answered. In this study, we aimed to investigate the relationship among the P stat, DOC and the strength of cavitation. Methods Ex vivo bovine liver tissues were immersed in degassed water with different DOC of 1.0 mg/L, 1.5 mg/L and 2.0 mg/L. Ultrasound (US) of 1 MHz and the spatial and temporal average intensity (I sata) of 6500 W/cm2 was used to expose two groups of in vitro bovine livers for 2 s; one group was under atmospheric pressure (P stat = 1 bar) and the other was under sub-atmospheric pressure (P stat = 0.1 bar). Acoustic cavitation was detected by a passive cavitation detector (PCD) during the exposure process. Echo signals at the focal zone of HIFU were monitored by B-mode ultrasound imaging before and after exposure. The difference between two pressure groups was tested using paired sample t-test. The difference among different DOC groups was evaluated by one-way analysis of variance (ANOVA). Results The results demonstrated a significant difference of broadband acoustic emissions from the cavitation bubbles, echo signals on B-mode image, morphology of lesions under various conditions of ambient pressure and DOC. The lesion volume in tissue was increased with the increase of ambient pressure and DOC. Conclusion Cavitation could be suppressed through sub-atmospheric pressure and low DOC level in liver tissue, which could provide a method of controlling cavitation in HIFU treatment to avoid unpredictable lesions.

ObjectivesSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) lineage B.1.617.2 (also named the Delta variant) was declared as a variant of concern by the World Health Organization (WHO). This study aimed to describe the outbreak that occurred in Nanjing city triggered by the Delta variant through the epidemiological parameters and to understand the evolving epidemiology of the Delta variant.MethodsWe collected the data of all COVID-19 cases during the outbreak from 20 July 2021 to 24 August 2021 and estimated the distribution of serial interval, basic and time-dependent reproduction numbers (R0 and Rt), and household secondary attack rate (SAR). We also analyzed the cycle threshold (Ct) values of infections.ResultsA total of 235 cases have been confirmed. The mean value of serial interval was estimated to be 4.79 days with the Weibull distribution. The R0 was 3.73 [95% confidence interval (CI), 2.66–5.15] as estimated by the exponential growth (EG) method. The Rt decreased from 4.36 on 20 July 2021 to below 1 on 1 August 2021 as estimated by the Bayesian approach. We estimated the household SAR as 27.35% (95% CI, 22.04–33.39%), and the median Ct value of open reading frame 1ab (ORF1ab) genes and nucleocapsid protein (N) genes as 25.25 [interquartile range (IQR), 20.53–29.50] and 23.85 (IQR, 18.70–28.70), respectively.ConclusionsThe Delta variant is more aggressive and transmissible than the original virus types, so continuous non-pharmaceutical interventions are still needed.

A series of natural product (2-phenyethyl)chromone analogues (3–34) were designed, synthesized, and screened for their α-glucosidase inhibitory activity. The results indicated that some of the synthesized derivatives displayed inhibitory activities against α-glucosidase with IC50 values ranging from 11.72 ± 0.08 to 85.58 ± 2.30 μM when compared to the standard drug acarbose (IC50 = 832.22 ± 2.00 μM). Among them, compound 4 with a hydroxyl group at the 7-position of chromone and a chloro group at the 4-position of the benzene ring, displayed the most significant inhibitory activity with the IC50 value of 11.72 ± 0.08 μM. The inhibitory mechanism of compound 4 against α-glucosidase was studied by enzyme kinetic, circular dichroism spectra, fluorescence quenching, and molecular docking. Sucrose loading test in vivo further demonstrated that it could decrease blood glucose levels after sucrose administration in normal Kunming mice. In vitro cytotoxicity showed that 4 exhibited low cytotoxicity against normal human cell lines. The ADME study suggested that all compounds are likely to be orally active as they obeyed Lipinski’s rule of five. In summary, our studies showed that these derivatives are a new class of α-glucosidase inhibitors.

PET/DIDOPO conjugated flame retardant composites were prepared by melt blending of styrene bridged DOPO (DIDOPO) into polyethylene terephthalate (PET). The flame retardancy, rheological behavior, and thermal degradation behavior of the composite were characterized by vertical combustion test (UL-94), limit oxygen index test (LOI), rotational rheometer, and thermogravimetry (TG). The results showed that the flame retardant composite with V-0 grade was obtained when the amount of DIDOPO is 12.5wt%, and the corresponding LOI value was 56.87% higher than that of PET. The thermogravimetry-fourier infrared spectroscopy (TG-FTIR) test results showed that DIDOPO could promote the degradation of PET/DIDOPO materials, and release phosphorus-containing free radicals to quench the flame, therefore slowing down the combustion process, and mainly playing the key flame retardant role in gas-phase.

To realize the triple functions of “roadway support, thermal insulation and heat regulation” of pumping wet shotcrete (PWS), the microencapsulated phase change material (MPCM) with poly (lauryl methacrylate) as shell and paraffin wax as core was synthetized by interfacial polymerization. The surface morphology, particle size distributions, core-shell compositions, the performances of the thermal stability and phase change of the MPCM were analyzed. The results show that the synthetized MPCM has excellent performances and can be applied in PWS. To obtain the optimal mixed proportions of the key materials (i.e., ceramsite, sand and MPCM) in PWS, the key performance indices were employed in the orthogonal experimental design to test the multiple performances of the PWS containing MPCMs. The results show that these performances are influenced by the dosages of the key materials and the recommended dosages were: 112.5 kg/m3 of ceramsite, 1250 kg/m3 of sand and 100 kg/m3 of MPCM. This study shows that the application of the MPCMs cannot only further reduce the thermal conductivity of PWS but also endow PWS with the function of heat regulation. A broad prospect of the application of MPCMs in underground cooling engineering can be expected.

The frequency of chronic cutaneous wounds are sharply increasing in aging populations. Patients with age-related diseases, such as diabetes, tumors, renal failure and stroke are prone to soft tissue and skin injury, compounded by slowed healing in aging. Imbalance of wound inflammation, loss of growth factor secretion, and impairment of tissue repair abilities are all possible reasons for failed healing. Therefore, it is vital to explore novel approaches to accelerate wound healing. Platelet-rich plasma (PRP) as a cell therapy has been widely applied for tissue repair and regeneration. PRP promotes wound healing by releasing antimicrobial peptides, growth factors and micro-RNAs. Medical evidence indicates that autologous platelet-rich plasma (au-PRP) can promote wound healing effectively, safely and rapidly. However, its clinical application is usually restricted to patients with chronic cutaneous wounds, generally because of other severe complications and poor clinical comorbidities. Allogeneic platelet-rich plasma (al-PRP), with abundant sources, has demonstrated its superiority in the field of chronic wound treatment. Al-PRP could overcome the limitations of au-PRP and has promising prospects in clinical applications. The aim of this review is to summarize the current status and future challenges of al-PRP in chronic cutaneous wound management. We also summarized clinical cases to further describe the application of al-PRP for chronic wounds in clinical practice.

Hepatocellular carcinoma (HCC) responds poorly to standard chemotherapy or targeted therapy; hence, exploration for novel therapeutic targets is urgently needed. CEP192 protein is indispensable for centrosome amplification, which has been extensively characterized in both hematological malignancies and solid tumors. Here, we combined bioinformatics and experimental approaches to assess the potential of CEP192 as a prognostic and therapeutic target in HCC. CEP192 expression increased with tumor stage and was associated with poor clinicopathologic features, frequent recurrence, and higher mortality. Upon single-cell RNA sequencing, CEP192 was found to be involved in the proliferation and self-renewal of hepatic progenitor-like cells. This observation was further evidenced using CEP192 silencing, which prevented tumor cell proliferation and self-renewal by arresting cells in the G0/G1 phase of the cell cycle. Notably, CEP192 was highly correlated with multiple tumor-associated cytokine ligand–receptor axes, including IL11–IL11RA, IL6–IL6R, and IL13–IL13RA1, which could promote interactions between hepatic progenitor-like cells, PLVAP+ endothelial cells, tumor-associated macrophages, and CD4+ T cells. Consequently, CEP192 expression was closely associated with an immunosuppressive tumor microenvironment and low immunophenoscores, making it a potential predictor of response to immune checkpoint inhibitors. Taken together, our results unravel a novel onco-immunological role of CEP192 in establishing the immunosuppressive tumor microenvironment and provide a novel biomarker, as well as a potential target for therapeutic intervention of HCC.

The transient receptor potential (TRP) channel is a type of channel protein widely distributed in peripheral and central nervous systems. Genes encoding TRP can be regulated by natural aromatic substances and serve as a therapeutic target for many diseases. However, the role of TRP-related genes in lung adenocarcinoma (LUAD) remains unclear. In this study, we used data from TCGA to screen and identify 17 TRP-related genes that are differentially expressed between LUAD and normal lung tissues. Based on these differentially expressed genes (DEGs), we classified all patients with LUAD into two subtypes. Significant differences in prognosis, clinical features, and immune cell infiltration characteristics were observed between the two subtypes. Subsequently, a prognostic signature with 12 genes was established by applying the least absolute shrinkage and selection operator (LASSO) Cox regression method, and all patients with LUAD were classified into low- and high-risk groups. Patients with LUAD in the low-risk group had a significantly longer survival time than those in the high-risk group (p < 0.001), which was confirmed by LUAD data from the GSE72094 and GSE68571 validation datasets. Combined with clinical characteristics, the risk score was found to be an independent predictor of overall survival (OS) in patients with LUAD. Additionally, patients with high TRP scores exhibited poorer clinical characteristics and immune status while showing a sensitive response to chemotherapeutic agents. In conclusion, the TRP score is a promising biomarker for determining the prognosis, molecular subtype, tumor microenvironment, and guiding personalized treatment in patients with LUAD.

Light and soil environments have extensive heterogeneity for many plants species affecting plant growth, reproduction, and distribution. However, the interaction effects of these two factors on the ecophysiological traits and adaptive strategy of plants remain largely unclear. In the present study, we set four shading levels and three soil types to investigate the effects of shade and soil type on seedlings growth, C:N:P stoichiometry responses, and nutrient use efficiency in Firmiana simplex (F. simplex). The maximum of total biomass was observed in acid purple soil under 75% shade, with a maximum difference of 3.6 times. With the increase in shading intensity, C content in the root, stem, and leaf reached maximum value under 75% shade. However, C content in the root and N content in the stem reached a maximum value of 420.6 g·kg−1 and 13.7 g·kg−1 in acid purple soil, respectively. With the increase in shading intensity, the total C and N accumulation showed a trend of progressive increase and then decrease, reaching the maximum value of 346.2 mg and 10.7 mg under 75% shade, respectively. The N:P ratios of various organ ranged from 3.1 to 11.9 in acid purple soil and red soil, indicating that the seedlings growth was restricted by nitrogen. We concluded that the interactions of shade and soil types might adjust the C:N:P stoichiometry and influence the dynamic balance between nutrients and organs in F. simplex seedlings.

A water-lubricated rubber bearing (WLRB) is prone to generate frictional vibration noise under special operating conditions, which seriously affects the acoustic stealth performance of warships and threatens their navigation safety. Meanwhile, the main factor affecting the frictional vibration behavior of a WLRB is the materials of the friction pair. Therefore, this work selects a friction pair composed of a copper ring and a rubber block as the research object and studies the frictional vibration behavior of the ring–block friction pair under low-speed and starting conditions. The real friction coefficient curve is used to establish a transient dynamic finite element analysis model for the ring–block friction pair. The effects of the load, friction coefficient, and Young’s modulus on the frictional vibration behavior under special operating conditions are studied. The analysis’s results show that the frequency of the medium-high frequency friction-induced vibration disappears under low-speed operating conditions when the friction coefficient is below 0.1. During the startup process, even if the friction coefficient is very low, the medium-high frequency friction-induced vibration still exists. The research results provide ideas for future theoretical research and guidance suggestions for engineering practice.

Abstract Background The TM4 (UBAC2) protein, which contains 4 transmembrane domains and one ubiquitin binding domain, is mainly expressed in cell and nuclear membranes. The current research aimed to explore the role of TM4 in metabolic inflammation and to examine whether the ubiquitin–proteasome inhibitor PS-341 could regulate the function of TM4. Methods The metabolic phenotypes of TM4 knockout (KO) mice were studied. We next explored the association between the polymorphisms of TM4 and obesity in a Chinese Han population. TM4 expression in the visceral fat of obese patients who underwent laparoscopic cholecystectomy was also analysed. Finally, the effect of PS-341 on the degradation and function of the TM4 protein was investigated in vivo and in vitro. Results TM4 KO mice developed obesity, hepatosteatosis, hypertension, and glucose intolerance under a high-fat diet. TM4 counterregulated Nur77, IKKβ, and NF-kB both in vivo and in vitro. The TM4 SNP rs147851454 is significantly associated with obesity after adjusting for age and sex (OR 1.606, 95% CI 1.065–2.422 P = 0.023) in 3394 non-diabetic and 1862 type 2 diabetic adults of Han Chinese. TM4 was significantly downregulated in the visceral fat of obese patients. PS-341 induced TM4 expression through inhibition of TM4 degradation in vitro. In db/db mice, PS-341 administration led to downregulation of Nur77/IKKβ/NF-κB expression in visceral fat and liver, and alleviation of hyperglycaemia, hypertension, and glucose intolerance. The hyperinsulinaemic-euglycaemic clamp demonstrated that PS-341 improved the glucose infusion rate and alleviated insulin resistance in db/db mice. Conclusions PS-341 alleviates chronic low-grade inflammation and improves insulin sensitivity through inhibition of TM4 degradation.

Global food security is threatened by rice blast disease caused by the filamentous fungus Magnaporthe oryzae. An understanding of rice resistance mechanisms is fundamental to developing strategies for disease control. In this review, we summarize recent advances in pathogen-associated molecular pattern-triggered immunity, effector-triggered immunity, defense regulator-mediated immunity, and effects of nutrient elements on rice blast resistance. We outline strategies used for breeding rice cultivars with improved disease resistance. We also present the major research challenges for rice blast disease resistance and propose approaches for future investigation.

Abstract Background Since the outbreak of COVID-19, it has been documented that old age and underlying illnesses are associated with poor prognosis among COVID-19 patients. However, it is unknown whether sarcopenia, a common geriatric syndrome, is associated with poor prognosis among older COVID-19 patients. The aim of our prospective cohort study is to investigate the association between sarcopenia risk and severe disease among COVID-19 patients aged ≥60 years. Method A prospective cohort study of 114 hospitalized older patients (≥60 years) with confirmed COVID-19 pneumonia between 7 February, 2020 and 6 April, 2020. Epidemiological, socio-demographic, clinical and laboratory data on admission and outcome data were extracted from electronic medical records. All patients were assessed for sarcopenia on admission using the SARC-F scale and the outcome was the development of the severe disease within 60 days. We used the Cox proportional hazards model to identify the association between sarcopenia and progression of disease defined as severe cases in a total of 2908 person-days. Result Of 114 patients (mean age 69.52 ± 7.25 years, 50% woman), 38 (33%) had a high risk of sarcopenia while 76 (67%) did not. We found that 43 (38%) patients progressed to severe cases. COVID-19 patients with higher risk sarcopenia were more likely to develop severe disease than those without (68% versus 22%, p

Background: Adaptor-related protein complex 3, sigma one subunit (AP3S1) is one of the encoding subunits of the adaptor complex AP-3. However, its role in various tumor types and relationship with the tumor immune microenvironment (TIME) remains unclear.Methods: AP3S1 expression was analyzed using datasets from The Cancer Genome Atlas, Genotype-Tissue Expression, UALCAN, and HPA databases. Then, we performed a systematic analysis of the genetic alterations, clinical features, and prognostic value of AP3S1 in pan-cancer. Gene set enrichment analysis (GSEA) and gene set variation analysis (GSVA) were used to identify the signaling pathways associated with AP3S1. The correlation between immune cell infiltration and AP3S1 expression was analyzed using immune cell infiltration data from the ImmuCellAI, TIMER2, and a previous study. Finally, we analyzed the association of AP3S1 with tumor mutational burden (TMB), microsatellite instability (MSI), and immune-related genes.Results: We found AP3S1 overexpression in most tumors and a significant association with low survival rates. GSEA and GSVA results show that AP3S1 is involved in tumor progression and associated with immune pathways in different tumor types. We also found that AP3S1 expression was positively correlated with the level of infiltration of immunosuppressive cells (tumor-associated macrophages, cancer-associated fibroblasts, Tregs) and negatively correlated with immune killer cells, including NK cells and CD8+ T cells, in pan-cancer. The expression of AP3S1 could affect TMB and MSI in various cancers. In addition, AP3S1 was positively correlated with most immunosuppressive genes, including PD-1, PD-L1, CTLA4, LAG3 and TIGIT in most cancer types.Conclusion: Our study reveals that AP3S1 is a potential pan-cancer oncogene and plays an essential role in tumorigenesis and cancer immunity. Elevated expression of AP3S1 indicates an immunosuppressive microenvironment and can be used as a potential prognostic biomarker and a target for immunotherapy.

The conjugated flame retardants have rarely been studied. A conjugate flame-retardant 4, 4'-{1″, 4″-phenylene-bis [amino- (10‴-oxy10‴-hydro-9‴-hydrogen- 10‴λ5-phosphaphenanthrene-10″-yl)-methyl]}-diphenol (P-PPD-Ph) was synthesized and added into the polylactic acid (PLA) matrix. The P-PPD-Ph-conjugated flame-retardant structure was tested by FTIR, 1H, and 31P NMR analysis. The thermal and rheological properties of PLA/P-PPD-PH-conjugated flame-retardant composites were investigated. The results showed that P-PPD-Ph-conjugated flame retardant affects PLA/P-PPD-PH-conjugated flame-retardant composites for promoting the formation of a carbon layer when the P-PPD-Ph-conjugated flame-retardant content was 15% and the residual carbon ratio for PLA/P-PPD-PH-conjugated flame-retardant composites increased by 4.2%.

Abstract People living with HIV (PLWH) bear higher prevalence of HCV coinfection. An accessible directly acting antivirals regimen with less drug–drug interaction with antiretroviral therapy (ART) is urgently needed in source limited regions. We aimed to assess the efficacy and safety of SOF + RBV for 24 weeks regimen in HIV–HCV coinfected patients in Liangshan Prefecture, China. PLWH under ART from China’s national free antiretroviral treatment project (CNFATP) and diagnosed with treatment-naïve HCV infection were enrolled. SOF + RBV was administrated for 24 weeks and patients were followed for ≥ 12 weeks. The efficacy and safety were analyzed and related factors were explored. 58 patients completed 24 weeks of SOF + RBV and had all tests done. Genotype prevalence in this population was G3 44.8% (n = 26), G6 31.0% (n = 18) and G1 17.2% (n = 10) respectively. 52/58 (89.7%) patients achieved SVR12 while 10.3% experienced therapeutic failure. However, SVR12 was neither significantly different between groups of different gender, age, transmission routines, CD4+ cell count, HIV infection duration, ART duration and HBsAg prevalence nor influenced by HCV viral load, genotypes and hepatic stiffness. The regimen was well-tolerated without any serious AEs or AEs leading to treatment adjustment or discontinuation reported. PLWH in Liangshan showed a high prevalence of HCV coinfection with GT3 and GT6 as the most frequent genotypes. SOF + RBV for 24 weeks could achieve good SVR12 in this population and was well-tolerated. It has great potential to be generalized in coinfected population in source-limited regions.

Increasing nitrogen (N) deposition profoundly affects nutrient cycling in soil, thereby influencing forest ecosystem productivity and function. Soil microorganisms are integral in driving nutrient turnover; the changes in microbial communities in response to N deposition and the associated soil nutrient availability, especially of limited nutrients, are far from clear. To explore the changes in soil bacterial and fungal communities and their key environmental drivers under N deposition, we conducted a multilevel field N addition experiment in a Castanopsis carlesii natural forest. Soil properties and bacterial and fungal communities were investigated. There were no significant changes in alpha diversities (presented as Chao1 and Shannon’s indexes) and beta diversities of bacteria and fungi among the three treatments. Consistently, the relative abundances of dominant bacterial phyla (i.e., Proteobacteria, Acidobacteria, Actinobacteria, Chloroflexi, and Planctomycetes) and fungal phyla (i.e., Basidiomycota, Ascomycota, and Rozellomycota) did not change following N addition. These results suggest that N deposition did not alter microbial community diversity and structure. In addition, the results of the Mantel test showed that soil pH, NO3−-N, dissolved organic N (DON), and total phosphorus (TP) predominantly influenced the community diversity and structure in bacteria, but not in fungi. Meanwhile, the relative abundance of some sensitive microbial genera, such as Bryobacter, Bradyrhizobium, Sorangium, and Archaeorhizomyces, were significantly decreased. These results indicate a decreased microbial ability for N fixation and P mobilization induced by N deposition. Moreover, there were significant relationships between Bryobacter, Bradyrhizobium, and Archaeorhizomyces and NO3−-N and available P (AP), suggesting that the responses of sensitive microbial groups to N deposition likely depend on the changes in available nutrients in soil, especially limited N or P. Collectively, 6 years of N addition had no significant influence on microbial communities, but some sensitive microbial groups were associated with N or P turnover. This finding emphasizes the critical roles of sensitive microbial species in meditating limited nutrient cycling in soil under climate change.

The accurate and efficient detection of power lines and towers in aerial drone images with complex backgrounds is crucial for the safety of power grid operations and low-altitude drone flights. In this paper, we propose a new method that enhances the deep learning segmentation model UNet algorithm called TLSUNet. We enhance the UNet algorithm by using a lightweight backbone structure to extract the features and then reconstructing them with contextual information features. In this network model, to reduce its parameters and computational complexity, we adopt DFC-GhostNet (Dubbed Full Connected) as the backbone feature extraction network, which is composed of the DFC-GhostBottleneck structure and uses asymmetric convolution to capture long-distance targets in transmission lines, thus enhancing the model’s extraction capability. Additionally, we design a hybrid feature extraction module based on convolution and a transformer to refine deep semantic features and improve the model’s ability to locate towers and transmission lines in complex environments. Finally, we adopt the up-sampling operator CARAFE (Content-Aware Re-Assembly of FEature) to improve segmentation accuracy by enhancing target restoration using contextual neighborhood pixel information correlation under feature decoding. Our experiments on public aerial photography datasets demonstrate that the improved model requires only 8.3% of the original model’s computational effort and has only 21.4% of the original model’s parameters, while achieving a reduction in inference speed delay by 0.012 s. The segmentation metrics also showed significant improvements, with the mIOU improving from 79.75% to 86.46% and the mDice improving from 87.83% to 92.40%. These results confirm the effectiveness of our proposed method.

In order to solve the difficulty in localization and poor signal-to-noise ratio (SNR) of the angled shear vertical wave (SV wave) electromagnetic acoustic transducer (EMAT) in cracks detection of high-temperature carbon steel forgings, a finite element (FE) model of the angled SV wave EMAT detection process was established, and the influence of specimen temperature on the EMAT excitation, propagation, and reception processes was analyzed. A high-temperature resistant angled SV wave EMAT was designed to detect carbon steel from 20 °C to 500 °C, and the influence law of the angled SV wave at different temperatures was analyzed. Then a circuit-field coupled FE model of angled SV wave EMAT in the carbon steel detection process based on the Barker code pulse compression technique was established, and the effects of the Barker code element length, impedance matching method, and matching component parameters on the pulse compression effect were analyzed. In addition, the noise suppression effect and the SNR of the crack-reflected wave in the tone-burst excitation method and the Barker code pulse compression technique were compared. The results show that the amplitude of the block-corner reflected wave decreases from 556 mV to 195 mV, and the SNR decreases from 34.9 dB to 23.5 dB when the specimen temperature increases from 20 °C to 500 °C. When the temperature is 500 °C, the SNR of the crack-reflected wave obtained by the Barker code pulse compression technique can be improved by 9.2 dB compared to the tone-burst excitation method with 16 synchronous averages. The study can provide technical and theoretical guidance for online crack detection for high-temperature carbon steel forgings.

Background: Acute kidney injury (AKI) commonly develops among traumatic brain injury (TBI) patients and causes poorer outcomes. We perform this study to explore the relationship between serum magnesium and the risk of AKI among TBI. Methods: TBI patients recorded in the Medical Information Mart for Intensive Care-III database were eligible for this research. The restricted cubic spline (RCS) was utilized to fit the correlation between serum magnesium level and the AKI. Univariate and subsequent multivariate logistic regression analysis were utilized to explore risk factors of AKI and confirmed the correlation between serum magnesium and AKI. Results: The incidence of AKI in included TBI was 21.0%. The RCS showed that the correlation between magnesium level and risk of AKI was U-shaped. Compared with patients whose magnesium level was between 1.5 and 2.0 mg/dL, those with a magnesium level of 2.0 mg/dL had a higher incidence of AKI. Multivariate logistic regression confirmed age, chronic renal disease, ISS, serum creatinine, vasopressor, mechanical ventilation, and serum magnesium

Background The killer cell immunoglobulin-like receptor (KIR), which mediates the killing function of NK cells, is an attractive candidate for adoptive cellular therapy. The ethnic distribution for China provides a unique opportunity to investigate KIR gene distribution. Aim The aim of this study was to explore the relationship between population history and the rapidly evolving KIR genetic diversity. Subjects and methods 8050 Chinese donors from 184 hospitals were included to analyse frequency, haplotype, and B-content data of 16 KIR genes, by PCR-SSP for KIR genotyping. Results KIR gene carrier frequencies were found similar to those observed in other studies on Han, but different from Thais, Japanese, Africans, and populations of West Eurasian ancestry. High-frequency KIR genotype profiles found in the present population were consistent with other studies on Han populations but different from those conducted on other cohorts. The majority of our cohort carried group A KIR gene motifs. Additionally, populations with similar geographic locations in China were shown clustered together, while Hainan and Xinjiang provinces were slightly separated from these. Conclusion The distribution of KIR genes varies by geographic region, and different ethnic groups may be a confounding factor of KIR diversity.

Abstract Background Chloroplast genome resources can provide useful information for the evolution of plant species. Tea plant (Camellia sinensis) is among the most economically valuable member of Camellia. Here, we determined the chloroplast genome of the first natural triploid Chinary type tea (‘Wuyi narcissus’ cultivar of Camellia sinensis var. sinensis, CWN) and conducted the genome comparison with the diploid Chinary type tea (Camellia sinensis var. sinensis, CSS) and two types of diploid Assamica type teas (Camellia sinensis var. assamica: Chinese Assamica type tea, CSA and Indian Assamica type tea, CIA). Further, the evolutionary mechanism of the chloroplast genome of Camellia sinensis and the relationships of Camellia species based on chloroplast genome were discussed. Results Comparative analysis showed the evolutionary dynamics of chloroplast genome of Camellia sinensis were the repeats and insertion-deletions (indels), and distribution of the repeats, indels and substitutions were significantly correlated. Chinese tea and Indian tea had significant differences in the structural characteristic and the codon usage of the chloroplast genome. Analysis of sequence characterized amplified region (SCAR) using sequences of the intergenic spacers (trnE/trnT) showed none of 292 different Camellia sinensis cultivars had similar sequence characteristic to triploid CWN, but the other four Camellia species did. Estimations of the divergence time showed that CIA diverged from the common ancestor of two Assamica type teas about 6.2 Mya (CI: 4.4–8.1 Mya). CSS and CSA diverged to each other about 0.8 Mya (CI: 0.4–1.5 Mya). Moreover, phylogenetic clustering was not exactly consistent with the current taxonomy of Camellia. Conclusions The repeat-induced and indel-induced mutations were two important dynamics contributed to the diversification of the chloroplast genome in Camellia sinensis, which were not mutually exclusive. Chinese tea and Indian tea might have undergone different selection pressures. Chloroplast transfer occurred during the polyploid evolution in Camellia sinensis. In addition, our results supported the three different domestication origins of Chinary type tea, Chinese Assamica type tea and Indian Assamica type tea. And, the current classification of some Camellia species might need to be further discussed.

Background: /Objective: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease, and effective treatments are lacking. Bariatric surgery, including sleeve gastrectomy (SG), is a potential therapeutic strategy for NAFLD, but the molecular mechanisms underlying its effects are not fully understood. In this study, the effects of SG and the underlying mechanisms were evaluated in a mouse model of high-fat diet (HFD)-induced NAFLD. Methods: C57BL/6 mice were randomly divided into three groups: normal diet with sham operation (NC-Sham group), HFD with sham operation (HFD-Sham group), and HFD with sleeve gastrectomy (HFD-SG group). Glucose metabolism and fat accumulation in the body and liver were analyzed before and after SG. Lipid metabolism and inflammation in the liver were evaluated. Nicotinamide adenine dinucleotide (NAD+) levels as well as nicotinamide riboside kinase (NRK1) and Sirtuin-1 (SIRT1) expression levels were evaluated. Results: SG attenuated the HFD-induced increases in glucose and insulin levels, fat accumulation, and lipid droplet accumulation. Fatty acid biosynthesis, the expression of the metabolism-related genes ACC1, FASN, SCD1, and DGAT1, and the levels of inflammatory factors were higher in HFD mice than in NC mice and decreased after SG. NAD + concentrations were 54.9 ± 13.4 μmol/mg in NC-Sham mice, 37.6 ± 8.1 μmol/mg in HFD-Sham mice, and 79.9 ± 13.0 μmol/mg in HFD-SG mice (p

A new series of sulphonamide derivatives bearing naphthalene moiety were synthesised and evaluated for their antiproliferative and tubulin polymerisation inhibitory activities. These new compounds were evaluated for their in vitro antiproliferative activity against MCF-7 and A549 by using CCK-8 method. Among all the tested compounds, compound 5c with naphthalen-1-yl moiety exhibited the most potent antiproliferative activity against MCF-7 and A549 cell line, with IC50 values of 0.51 ± 0.03 µM and 0.33 ± 0.01 µM, respectively. The results of tubulin polymerisation assay shown that 5c exhibited a significant ability to inhibit tubulin polymerisation with IC50 value of 2.8 μM. Consistent with its antitubulin activity, 5c can significantly arrest the cell cycle at G2/M phase and induce apoptosis in MCF-7 cancer cells. Molecular docking study indicated that compound 5c inhibited tubulin polymerisation through interacting at the colchicine-binding site of tubulin. Furthermore, 5c exhibited low cytotoxic activity on human normal cell line.

A novel series of thiazole-naphthalene derivatives as tubulin polymerisation inhibitors were designed, synthesised, and evaluated for the anti-proliferative activities. The majority of the tested compounds exhibited moderate to potent antiproliferative activity on the MCF-7 and A549 cancer cell lines. Among them, compound 5b was found to be the most active compound with IC50 values of 0.48 ± 0.03 and 0.97 ± 0.13 μM. Moreover, mechanistic studies revealed that 5b significantly inhibited tubulin polymerisation with an IC50 value of 3.3 µM, as compared to the standard drug colchicine (IC50 = 9.1 μM). Further cellular mechanism studies elucidated that 5b arrested the cell cycle at G2/M phase and induced apoptosis in MCF-7 cancer cells. Molecular modelling study indicated that 5b binds well to the colchicine binding site of tubulin. In summary, these results suggest that 5b represents a promising tubulin polymerisation inhibitor worthy of further investigation as potential anticancer agents.