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Backgroud: Many dyes or radioactive markers used for sentinel lymph node (SLN) have the shortcomings of false positive and radiation injury. Indocyanine green (ICG) seems to have a lower false positive rate and tissue damage, without a clear field of vision during the operation. Methods: For the shortcomings, we successfully synthesized three anionic pullulan materials, changed the degree of hydrophobic for size controlling (< 50nm) to prepare CHP nanoparticles (NPs) and changed the succinyl degree to prepare CHPC NPs with different negative surface potential. Results: The size of those NPs were less than 50nm under (transmission electron microscope) TEM, with hydrodynamic size of 90.67±2.2nm of CHP, 105.8±1.7nm of CHPC1 and 115.9±2.3nm of CHPC2. Moreover, the Zeta potential of CHP, CHPC1 and CHPC2 were -1.9±0.2mV, -9.6±0.3mV and -19.4±0.7mV. The size of ICG-loading CHP, CHPC1 and CHPC2 NPs increased to 109.4±2.7nm, 113.8±1.2nm and 30.6±3.5 nm, as the zeta potential decreased to -2.7±0.4mV, -12.5±1.6mV and -23.1 ±1.2mV. With the increasing degree of succinyl, the size increased and the zeta potential decreased. At the same time, the higher degree of succinyl drug-loading NPs have lower release and have increased the stability of ICG. We found that the blank-NPs had no significant toxicity to normal cells (HSF), as the ICG@CHP group had larger toxicity than the CHPCs and control. Moreover, the cellular uptake was decreased with the increased degree of succinyl. Conclusion: In this study, we successfully prepared CHPC2 carriers with the maximum negative surface charge, for follow-up research and providing new ideas for SLN.

Reported herein is a novel palladium-catalyzed [2 + 2 + 1] domino annulation of 3-iodochromones, bridged olefins, and dimethyl squarate allowing the construction of chromone-containing polycyclic compounds in good to high yields. Importantly, dimethyl squarate is first employed as the solid C1 source in organic synthesis. Gram-scale experiments, late-stage modification of natural products, as well as transformations of products show potential for further synthetic elaborations.

Injecting CO2 into hydrocarbon reservoirs can enhance the recovery of hydrocarbon resources, and simultaneously, CO2 can be stored in the reservoirs, reducing considerable amount of carbon emissions in the atmosphere. However, injected CO2 tends to go through fractures, high-permeability channels and streaks present in reservoirs, resulting in inefficient hydrocarbon recovery coupled with low CO2 storage performance. Conformance treatments with CO2-resistant crosslinked polymer gels were performed in this study to mitigate the CO2 channeling issue and promote the synergy between enhanced oil recovery (EOR) and subsurface sequestration of CO2. Based on a typical low-permeability CO2-flooding reservoir in China, studies were performed to investigate the EOR and CO2 storage performance with and without conformance treatment. The effect of permeability contrast between the channels and reservoir matrices, treatment size, and plugging strength on the efficiency of oil recovery and CO2 storage was systematically investigated. The results indicated that after conformance treatments, the CO2 channeling problem was mitigated during CO2 flooding and storage. The injected CO2 was more effectively utilized to recover the hydrocarbons, and entered wider spectrum of pore spaces. Consequently, more CO2 was trapped underground. Pronounced factors on the synergy of EOR and CO2 storage were figured out. Compared with the treatment size, the CO2 storage efficiency was more sensitive to the plugging strength of the conformance treatment materials. This observation was important for conformance treatment design in CCUS-EOR projects. According to this study, the materials should reduce the channel permeability to make the channel/matrix permeability ratio below 30. The results demonstrate the importance of conformance treatment in maximizing the performance of CCUS-EOR process to achieve both oil recovery improvement and efficient carbon storage. This study provides guidelines for successful field applications of CO2 transport control in CO2 geo-utilization and storage.

The study examines how surface acting and deep acting affect emotional exhaustion and job performance in the hotel industry and whether emotional intelligence has a moderating effect on the relationship. The study was conducted using a questionnaire survey, and the data were analyzed using a structural equation model. The main findings of the study demonstrate that surface acting has no effect on emotional exhaustion while deep acting has a negative effect on emotional exhaustion. This indicates that deep acting not only produces better service performance but also reduces emotional exhaustion. Moreover, surface acting and deep acting both have a positive effect on job performance, showing that both acting skills are all about demonstrating a better job performance at work. Furthermore, emotional intelligence has a moderating effect on the relationships between surface acting and job performance and deep acting and job performance, this indicates that employees with higher emotional intelligence are more likely to perform a more effective outcome of acting on job performance, regardless of whether it is surface acting or deep acting. But this phenomenon only occurs when employees are not experiencing emotional exhaustion. If employees are already experiencing emotional exhaustion, emotional intelligence does not have any moderation effect on job performance.

Background: Noise-induced hearing impairment can mediate delayed injury of spiral neurons (SGNs), resulting in degeneration of nerve fibers, synaptic degeneration and even death of SGNs. We believe that delayed injury is related to mitochondrial energy metabolism disorders. Results: We investigated ATP and the electron transport chain (ETC) in rat SGNs after noise injury and found that with prolonged injury time, ATP synthesis and the expression of complexes II and IV decreased, indicating the functional decline of the ETC. The maintenance of ETC function is related to subunit import and assembly of the complex. The disulfide relay mechanism controlled by the apoptosis inducing factor/coiled-coil-helix-coiled-coil-helix domain-containing protein 4（AIF/CHCHD4) pathway can regulate mitochondrial protein import. The results showed that AIF expression in SGNs decreased after noise exposure, indicating that noise damage to SGNs can restoreintramitochondrial protein input by downregulating the AIF/CHCHD4 pathway, hinderingETC function. Conclusion: After noise injury, the mitochondrial function markers, ATP and complexes II/IV down-expressed , indicating insufficiency of ECT function leaded to delay injured SGNs. And the down-regulation of AIF/CHCHD4 function was a possible mechanism that hindered ECT function.

The WHO declared to eliminate hepatitis B virus (HBV) by 2030. However, an increasing number of patients are presenting with low-level viremia (LLV) with the widespread use of antiviral medications. The diagnostic efficiency and coverage area of HBV infection are low. Hence, this study intended to drive the HBV infection detection to effectively adaptable for any small to medium-sized laboratory or field survey. We established, optimized, and evaluated a colloidal gold test strip for detection of HBV DNA based on CRISPR/Cas13a combined with recombinase-aided amplification (RAA) technology. Furthermore, 180 HBV-infected patients (including patients with different viral loads, LLV patients and dynamic plasma samples of patients on antiviral therapy) were enrolled for clinical validation. The strip detection of HBV DNA was established based on RAA-CRISPR-Cas13a technology with a sensitivity of 101 copies/μL and a specificity of 100%. HBV DNA gradient concentration plasmids and clinical samples were effectively identified by this approach. The positive coincidence rate for LLV patients was 87%, while the negative coincidence rate was 100%. The positive coincidence rate reached 100% in LLV patients (viral loading >100 IU/mL). The sensitivity, specificity, positive predictive agreement (PPA) and negative predictive agreement (NPA) values of dynamic plasma detection in patients on antiviral therapy were 100%, 92.15%, 93.75%, and 100%, respectively. We develop rapid and portable RAA-CRISPR/Cas13a-based strip of HBV DNA detection for LLV patients. This study provides a visual and faster alternative to current PCR-based diagnosis for HBV infection.

Additional file 1.

Quantum state transfer (QST) through spin chains has been extensively investigated. Two schemes, the coupling set for perfect state transfer (PST) or adding a leakage elimination operator (LEO) Hamiltonian have been proposed to boost the transmission fidelity. However, these ideal schemes are only suitable for closed systems and will lose their effectiveness in open ones. In this work, we invoke a well explored optimization algorithm, Adam, to expand the applicable range of PST couplings and LEO to the open systems. Our results show that although the transmission fidelity decreases with increasing system-bath coupling strength, Markovianity and temperature for both ideal and optimized cases, the fidelities obtained by the optimized schemes always outweigh the ideal cases. The enhancement becomes more bigger for a stronger bath, indicating a stronger bath provides more space for the Adam to optimize. This method will be useful for the realization of high-fidelity information transfer in the presence of environment.

Spiking neural networks(SNNs) can potentially offer an efficient way of performing inference because the neurons in the networks are sparsely activated and computations are event-driven. SNNs with higher accuracy can be obtained by converting deep convolutional neural networks(CNNs) into spiking CNNs. However, there is always a performance loss between CNN and its spiking equivalents, because approximation error occurs in the conversion from the continuous-valued CNNs to the sparsely firing, event-driven SNNs. In this paper, the differences between analog neurons and spiking neurons in neuron models and activities are analyzed, the impact of the balance between weight and threshold on the approximation error is clarified, and an adaptive threshold mechanism for improved balance between weight and threshold of SNNs is proposed. In this method, the threshold can be dynamically adjusted adapting to the input data, which makes it possible to obtain as small a threshold as possible while distinguishing inputs, so as to generate sufficient firing to drive higher layers and consequently can achieve better classification. The SNN with the adaptive threshold mechanism outperforms most of the recently proposed SNNs on CIFAR10 in terms of accuracy, accuracy loss and network latency, and achieved state-of-the-art results on CIFAR100.

Yuan-Yuan Liu,1,2 Ren-Feng Zhao,2 Chao Liu,2 Jie Zhou,2 Liu Yang,2 Li Li1 1Department of Gynecologic Oncology, Guangxi Medical University Cancer Hospital, Key Laboratory of Early Prevention and Treatment for Regional High Frequency Tumor, Ministry of Education, Nanning, Guangxi, People’s Republic of China; 2The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Yuan-Yuan Liu; Li Li Tel +86-13877152206; +86-13878113406Email 43322045@qq.com; yuanyuan_liu2021@163.comObjective: Nomograms are statistics-based predictive tools that integrate predictive factors. Herein, a nomogram was developed and validated to predict the overall survival (OS) in serous ovarian cancer (SOC).Methods: Primary SOC patients with satisfactory cytoreductive surgery, chemotherapy, and OS ≥ 1 month were included in this study. A total of 6957 patients from the Surveillance, Epidemiology, and End Results (SEER) database comprised the training group and 1244 patients comprised the external validation group. The nomogram was structured on Cox models and evaluated in both the training and validation groups using consistency index, area under the receiver operating characteristics curve, calibration plots, and risk subgroup classification. Kaplan–Meier curves were plotted to compare the survival outcomes between subgroups. A decision-curve analysis was used to test the clinical value of the nomogram.Results: Independent factors, including age, tumor grade, and Federation of Gynecology and Obstetrics (FIGO) stage, identified by multivariate analysis in the training cohort, were selected for the nomogram. The consistency indexes for OS were 0.689 in the training cohort and 0.639 in the validation cohort. The calibration curves showed good consistency between predicted and actual 3- and 5-year OS. Significant differences were observed in the survival curves of different risk subgroups. The decision-curve analysis indicated that our nomogram was superior to the American Joint Committee on Cancer (AJCC) staging system.Conclusion: A nomogram was constructed to predict the long-term OS in SOC and verified in Asians. The accurate predictions facilitated personalized treatments and follow-up strategies.Keywords: nomograms, serous ovarian cancer, overall survival, SEER, external verification

Studies have shown that phosphatase and tensin homolog deleted on chromosome ten (PTEN) participates in the regulation of cochlear hair cell survival. Bisperoxovanadium protects against neurodegeneration by inhibiting PTEN expression. However, whether bisperoxovanadium can protect against noise-induced hearing loss and the underlying mechanism remains unclear. In this study, we established a mouse model of noise-induced hearing loss by exposure to 105 dB sound for 2 hours. We found that PTEN expression was increased in the organ of Corti, including outer hair cells, inner hair cells, and lateral wall tissues. Intraperitoneal administration of bisperoxovanadium decreased the auditory threshold and the loss of cochlear hair cells and inner hair cell ribbons. In addition, noise exposure decreased p-PI3K and p-Akt levels. Bisperoxovanadium preconditioning or PTEN knockdown upregulated the activity of PI3K-Akt. Bisperoxovanadium also prevented H

The rise of India and China is a major historical developmental trend that has led to peaceful India-China media cooperation. From a long-term strategic point of view, the Indian and Chinese media platforms should seek common ground while overcoming differences and increasing mutual trust. The governments of India and China should grasp the dominant power of public opinion in traditional media, new media and self-media platforms. We must increase the number of each other's reporting stations and media branches to promote the "opposite column" in the content of the mainstream media. Meanwhile both sides should strengthen the training of reporters and journalist, thus improve the existing India-China media cooperation systems and gradually cut mutual misunderstandings by building friendly provinces, sister cities, and cultural and tourism exchange projects to jointly serve the two countries' national strategy for the smooth realization of a peaceful rise.

Noise-induced hearing impairment can mediate delayed injury of spiral neurons (SGNs), resulting in degeneration of nerve fibers, synaptic degeneration and even death of SGNs. We believe that delayed injury is related to mitochondrial energy metabolism disorders. Therefore, we investigated ATP and the electron transport chain (ETC) in rat SGNs after noise injury and found that with prolonged injury time, ATP synthesis and the expression of complexes II and IV decreased, indicating the functional decline of the ETC. The maintenance of ETC function is related to subunit import and assembly of the complex. The disulfide relay mechanism controlled by the apoptosis inducing factor/coiled-coil-helix-coiled-coil-helix domain-containing protein 4(AIF/CHCHD4) pathway can regulate mitochondrial protein import. The results showed that AIF expression in SGNs decreased after noise exposure, indicating that noise damage to SGNs can restore intramitochondrial protein input by downregulating the AIF/CHCHD4 pathway, hindering ETC function; insufficient ETC function is a possible reason for the delayed injury of SGNs.

(1) Background: Strains HL1 and M1, isolated from kefir grains, have been tentatively identified, based on their partial 16S rRNA gene sequences, as

Ammonia borane (AB) hydrolysis is a comparative strategy for developing the sustainable hydrogen economy. Considering the hydrolysis cannot occur kinetically at low temperature, a suitable catalyst is indispensable. In this work, the dispersed ruthenium nanoparticles are stabilized on hexagonal boron nitride (h-BN) via an adsorption-in situ reduction procedure. Various characterization techniques are adopted for elucidating the structure-performance relationship of the obtained catalysts for the hydrolytic dehydrogenation of AB. In the presence of the resultant Ru/h-BN catalysts, the corresponding turnover frequency (1177.5 min−1) in alkaline solution at 303 K and the apparent activation energy (24.1 kJ mol−1) are superior to most literature previously reported. Our work provides a facile fabrication method for metal-based catalysts, which are highly promising in chemical storage material hydrolysis.

Although multivalent glycosidase inhibitors have shown enhanced glycosidase inhibition activities, further applications and research directions need to be developed in the future. In this paper, two positional isomeric perylene bisimide derivatives (PBI-4DNJ-1 and PBI-4DNJ-2) with 1-deoxynojirimycin conjugated were synthesized. Furthermore, PBI-4DNJ-1 and PBI-4DNJ-2 showed positional isomeric effects on the optical properties, self-assembly behaviors, glycosidase inhibition activities, and hypoglycemic effects. Importantly, PBI-4DNJ-1 exhibited potent hypoglycemic effects in mice with 41.33 ± 2.84 and 37.45 ± 3.94% decreases in blood glucose at 15 and 30 min, respectively. The molecular docking results showed that the active fragment of PBI-4DNJ-1 has the highest binding energy (9.649 kcal/mol) and the highest total hydrogen bond energy (62.83 kJ/mol), which were related to the positional isomeric effect on the hypoglycemic effect in mice. This work introduced a new means to develop antihyperglycemic agents in the field of multivalent glycomimetics.

Ren-Feng Song,1,* Yu-Xia Jiang,2,* Jian-Chun Cui,3 Xue-Wei Yu,1 Yang Gao,3 Li Li,3 Xiao-Hua Pei4 1Department of General Surgery, The First People’s Hospital of Huangzhong District, Xining, 811600, People’s Republic of China; 2Department of Thyroid and Breast Surgery, The Chinese Medicine Hospital of Shexian, Handan, 056400, People’s Republic of China; 3Department of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), Shenyang, 110015, People’s Republic of China; 4Department of General Surgery, Xiamen Hospital of Beijing University of Traditional Chinese Medicine, Xiamen, 361001, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jian-Chun CuiDepartment of Thyroid and Breast Surgery, People’s Hospital of China Medical University (Liaoning Provincial People’s Hospital), No. 33 of Wenyi Street, Shenhe District, Shenyang, 110015, People’s Republic of ChinaTel/Fax +86-24 24016014Email cui_jc8e@163.comXiao-Hua PeiDepartment of Surgery, Xiamen Hospital of Beijing University of Traditional Chinese Medicine, No. 1739 of Xianyue Street, Huli District, Xiamen, 361001, People’s Republic of ChinaTel/Fax +86-592 5579686Email pxhertt@163.comObjective: This study aims to investigate the feasibility of the horizontal rotary-cut technique in the removal of superficial benign breast tumors with a ≤ 1.0 cm distance between the upper margin of the tumor and the skin.Patients and Methods: A total of 69 patients with superficial benign breast tumors received horizontal rotary-cut surgery between July 2018 and June 2019 (horizontal group). The rotary cutter groove was in the true lateral position of the tumor and the ultrasonic probe was vertical to the rotary cutter groove. The patients were compared with 33 patients who underwent the traditional vertical rotary-cut surgery between July 2017 and June 2018 (traditional group) regarding the aspects of operation time, intraoperative bleeding volume, postoperative skin ecchymosis, skin damage, and tumor residue. The rotary cutter groove was directly below the tumor and the ultrasonic probe was parallel to the rotary cutter groove in the traditional vertical rotary-cut surgery.Results: The operation time in the horizontal group was significantly shorter than in the traditional group (7.7 ± 1.1 minutes vs 9.5 ± 1.3 minutes, with t = − 7.458 and p = 0.000) and there was significantly less skin damage in the horizontal group than in the traditional group (0 cases vs 3 cases, with p = 0.032). The differences in intraoperative bleeding and postoperative skin ecchymosis between the two groups were not statistically significant (6.0 ± 1.3 mL vs 6.5 ± 1.5 mL, with t = − 1.853 and p = 0.067; 4 cases vs 2 cases, with χ2 = 0.003 and p = 0.958). Ninety-seven patients attended follow-ups for 6– 30 (16.5 ± 4.5) months. No residues or recurrences were observed under ultrasound reviews in either group.Conclusion: In superficial benign breast tumor removal, the horizontal rotary-cut breast technique can help avoid skin injury, shorten the operation time, and reduce tumor residue more effectively compared with the traditional vertical rotary-cut technique. It has certain popularization and application values.Keywords: three-dimensional stereotaxis, horizontal, rotary-cut/rotary cutting, superficial, breast tumors/masses

Background Hepatocellular carcinoma (HCC) is a long-term malignancy that causes high morbidities and mortalities worldwide. Notably, long non-coding RNAs (LncRNAs) have been identified as candidate targets for malignancy treatments. Methods LncRNA LINC01116 and its Pearson-correlated genes (PCGs) were identified and analyzed in HCC patients. The diagnostic and prognostic value of the lncRNA was evaluated using data from The Cancer Genome Atlas (TCGA). Further, we explored the target drugs of LINC01116 for clinical application. Relationships between immune infiltration and PCGs, methylation and PCGs were explored. The diagnostic potentials were then validated by real time-PCR and Oncomine cohorts. Results LINC01116 and the PCG OLFML2B are differentially and highly expressed in tumor tissues (both P ≤ 0.050). We found that LINC01116, TMSB15A, PLAU, OLFML2B, and MRC2 have diagnostic potentials (all AUC ≥ 0.700, all P ≤ 0.050) while LINC01116 and TMSB15A have prognostic significance (both adjusted P ≤ 0.050). LINC01116 was enriched in the vascular endothelial growth factor (VEGF) receptor signaling pathway, mesenchyme morphogenesis, etc.. After that, candidate target drugs with potential clinical significance were identified: Thiamine, Cromolyn, Rilmenidine, Chlorhexidine, Sulindac_sulfone, Chloropyrazine, and Meprylcaine. Analysis of immune infiltration revealed that MRC2, OLFML2B, PLAU, and TMSB15A are negatively associated with the purity but positively associated with the specific cell types (all P MRC2, OLFML2B, and PLAU have differential and high methylation levels in primary tumors (all P OLFML2B (RT-PCR and Oncomine) were consistent with those obtained in the TCGA cohort (all P 0.700). Conclusions Differentially expressed LINC01116 could be a candidate diagnostic and an independent prognostic signature in HCC. Besides, its target drugs may work for HCC therapy via the VEGF receptor signaling pathway. Differentially expressed OLFML2B could be a diagnostic signature involved in HCC via immune infiltrates.

Background/Aim: Recently, an increase in the number of asymptomatic rare benign liver tumors (BLTs) has been reported during health check-ups. It is difficult to determine the nature of partial rare BLTs and not easy to distinguish from malignant liver tumors. This study aimed to analysis clinical features, diagnosis, and treatment of rare BLTs to reduce misdiagnosis and provide reference for clinical practice.Methods: From January 2012 to January 2021, we treated 112 rare BLTs by hepatectomy, including 54 focal nodular hyperplasia, 14 hepatocellular adenoma, 28 hepatic angiomyolipoma, 3 hepatic granuloma, 2 inflammatory pseudotumor of the liver, 2 nodular regenerative hyperplasia, 2 hepatic lipoma, 1 solitary fibrous tumor of the liver, 1 hepatic schwannoma and 1 hepatic myelolipoma.Results: The majority of patients were middle-aged female and asymptomatic. Single tumors were dominant. The diagnostic accuracies of computed tomography (CT) and magnetic resonance imaging (MRI) were 32.5% and 44.2%, respectively. The majority of tumors were likely to be misdiagnosed as hepatocellular carcinoma (HCC) or difficult to distinguish from HCC. All patients underwent surgical treatment. Postoperative pathological and immunohistochemical examination can confirm the diagnosis. No patients without tumor recurrence or metastasis during follow up period.Conclusion: Altogether, the clinical symptoms of rare BLTs lack specificity, and their preoperative diagnosis largely depends on imaging examination, with a low diagnostic accuracy rate and high chances of misdiagnosis as HCC. Diagnosis is confirmed by pathological and immunohistochemical examination. Surgical resection for rare BLT is safe and effective, regular postoperative follow-up is necessary.

Transforming growth factor (TGF-β) plays an important role in the development of deer antlers. The purpose of this study was to investigate the role of long noncoding RNA in the transcriptional regulation of TGF-β1 and its relationship with the proliferation and differentiation of antler chondrocytes. High-throughput sequencing was used to screen lncRNAs related to TGF-β1. Next, the overexpression plasmid and interference sequence of target lncRNA27785.1 were constructed and transfected into chondrocytes. We found that lncRNA27785.1 inhibited the proliferation and migration of chondrocytes and delayed the transition of cells from G1 to S phase. qRT-PCR and Western blot analysis indicated that the overexpression of lncRNA27785.1 may downregulate mRNA and protein expression of TGF-BR2, Smad3, pSmad3, and Smad4. Our findings highlight lncRNA27785.1 as an inhibitor of chondrocytes proliferation and differentiation by negatively regulating the TGF-β/Smad signaling pathway; this implicates an important regulatory role for long noncoding RNA in the regeneration of antler.

Two new triterpenoid saponins, ardisicrenoside R and S (1 and 2), and one new phenylpropanoid glycoside, ardicrephenin (3), along with five known compounds (4-8), were isolated from roots of Ardisia crenata. Their structures were elucidated on the basis of NMR spectroscopic data and chemical methods. Compounds 2-7 were evaluated for their cytotoxic activities against A549, MCF-7, HepG2 and MDA-MB-231 cell lines by MTT assay. Ardicrenin (6) showed significant cytotoxicity, with IC50 values of 1.17 ± 0.01, 1.19 ± 0.06, 3.52 ± 0.23, and 16.61 ± 1.02 μmol·L-1, respectively.

The worldwide pandemics are the common enemy of all mankind.When faced with the global pandemics, it becomes necessary for all nations to strengthen cooperation.Although India and China are close neighbors in Asia,their media coverage of each other in 2020 was extremely asymmetrical.Nonetheless,this media coverage should be strengthening communication and cooperation.Only in this way can it benefit the people of the two nations and ultimately realize a coprosperity and collaborative development.

Thirty-two new diosgenin derivatives were designed, synthesized, and evaluated for their cytotoxic activities in three human cancer cell lines (A549, MCF-7, and HepG2) and normal human liver cells (L02) using an MTT assay in vitro. Most compounds, especially 8, 18, 26, and 30, were more potent when compared with diosgenin. The structure-activity relationship results suggested that the presence of a succinic acid or glutaric acid linker, a piperazinyl amide terminus, and lipophilic cations are all beneficial for promoting cytotoxic activity. Notably, compound 8 displayed excellent cytotoxic activity against HepG2 cells (IC50 = 1.9 μM) and showed relatively low toxicity against L02 cells (IC50 = 18.6 μM), showing some selectivity between normal and tumor cells. Studies on its cellular mechanism of action showed that compound 8 induces G0/G1 cell cycle arrest and apoptosis in HepG2 cells. Predictive studies indicated that p38α mitogen-activated protein kinase (MAPK) is the optimum target of 8 based on its 3D molecular similarity, and docking studies showed that compound 8 fits well into the active site of p38α-MAPK and forms relatively strong interactions with the surrounding amino acid residues. Accordingly, compound 8 may be used as a promising lead compound for the development of new antitumor agents.

Patients with ovarian cancer who receive platinum-based chemotherapy typically develop platinum resistance, which leads to tumor recurrence and mortality. Therefore, finding the underlying mechanisms and biomarkers is critical. A total of 51 platinum-resistant and 70 platinum-sensitive ovarian cancer patients were enrolled in this study. We examined the GSE131978 dataset in the National Center for Biotechnology Information (NCBI) Gene Expression Omnibus database for differentially expressed long non-coding RNAs and messenger RNAs (mRNAs) between platinum-resistant and platinum-sensitive patients and completed a microRNA chip analysis. After filtering by Pearson correlation analysis, the competitive endogenous RNA (ceRNA) networks were subsequently constructed. Then, the Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology enrichment analyses about mRNAs in ceRNA networks were accomplished. More crucially, we demonstrated the differentially expressed microRNAs using quantitative real-time PCR and fluorescence in situ hybridization. The feasibility of microRNAs as biomarkers to predict platinum resistance and tumor recurrence was assessed using the receiver operating characteristic curve and survival analysis. MiR-320b and miR-320d exhibited high area under the curve values of 0.757 and 0.702, respectively. In our study, ceRNA networks including miR-320b and miR-320d probably provided novel insights for platinum resistance in ovarian cancer patients.

Introduction: Recently, big data attract great attention from industries, academia, and governments. Education big data from teaching and learning processes used to assess elementary education level is scarce in China. Case description: Gansu province, located in the northwest China, is one of the most backward economy areas where the development of elementary English education falls far behind developed areas of the country. Taking Gansu province as a case study and English subject in senior high schools as the study object, we use score data of English academic proficiency test (2018-2020) from 322 senior high schools to explore spatial-temporal differences of English education level among those schools in order to promote the balanced development of regional education. First we briefly describe the generation of English big data from senior high schools, and then, we mine the big data to analyze the difference of the English education level using the anomaly method, the comparison method, the cluster analysis method, and hot point analysis method. English excellence degree is developed as an indicator to assess elementary English education level. Discussion and Evalution: The results show that: (1) there exists obvious difference in English education level among the selected senior high schools: the highest average value of English excellence degree is 759 times the lowest, and the number of schools with negative anomalies accounts for more than 50%; (2) English excellence degree displays an obvious agglomeration characteristic in Lanzhou city, the provincial capital, that is, the hot spots (high English level) of English excellence degree are located in Lanzhou, while the cold spots (low English level) are concentrated in minority and poor areas such as Linxia autonomous region, the major part of Longnan and the eastern part of Qingyang; (3) The investigation in the form of questionnaires confirms the fact that disadvantage schools in English level are usually lack of good teachers who have a preference to teach in areas with good conditions. Conclusion: From the results, we can draw the conclusion that big data play an important role in quantitatively assessing basic education level, which lays foundation for improving the regional education level. Individuals’ value orientation of study, attitude towards study and the study behavior will be investigated in the future.

The compiling of quantum gates is crucial for the successful quantum algorithm implementations. The environmental noise as well as the bandwidth of control pulses pose a challenge to precise and fast qubit control, especially in a weakly anharmonic system. In this work, we propose an algorithm to approximately compile single-qubit gates with arbitrary accuracy. Evaluation results show that the overall rotation distance generated by our algorithm is significantly shorter than the commonly used $U3$ gate, then the gate time can be effectively shortened. The requisite number of pulses and the runtime of scheme design scale up as $\mathcal{O}[\mathrm{Log}(1/\epsilon)]$ with very small prefactors, indicating low overhead costs. Moreover, we explore the trade-off between effectiveness and cost, and find a balance point. In short, our work opens a new avenue for efficient quantum algorithm implementations with contemporary quantum technology., Comment: 5 pages, 2 figures

Supplementary Notes and Figures

Plasmonics is a rapid growing field, which has enabled both fundamental science and inventions of various quantum optoelectronic devices. An accurate and efficient method to calculate the optical response of metallic structures with feature size in the nanoscale plays an important role. Quantum hydrodynamic theory (QHT) provides an efficient description of the free-electron gas, where quantum effects of nonlocality and spill-out are taken into account. In this work, we introduce a general QHT that includes diffusion to account for the broadening, which is a key problem in practical applications of surface plasmon. We will introduce a density-dependent diffusion coefficient to give very accurate linewidth. It is a self-consistent method, in which both the ground and excited states are solved by using the same energy functional, with the kinetic energy described by the Thomas-Fermi and von Weizs\"{a}cker (vW) formalisms. In addition, our QHT method is stable by introduction of an electron density-dependent damping rate. For sodium nanosphere of various sizes, the plasmon energy and broadening by our QHT method are in excellent agreement with those by density functional theory and Kreibig formula. By applying our QHT method to sodium jellium nanorods, we clearly show that our method enables a parameter-free simulation, i.e. without resorting to any empirical parameter, such as size-dependent damping rate and diffusing coefficient. It is found that there exists a perfect linear relation between the resonance wavelength and aspect radio. The width decreases with increasing aspect ratio and height. The calculations show that our QHT method provides an explicit and unified way to account for size-dependent frequency shifts and broadening of arbitrarily shaped geometries. It is reliable and robust with great predicability, and hence provides a general and efficient platform to study plasmonics.

This work proposes a novel malware identification model that is based on a graph neural network (GNN). The function call relationship and function assembly content obtained by analyzing the malware are used to generate a graph that represents the functional structure of a malware sample. In addition to establishing a multi-classification model for predicting malware family, this work implements a similarity model that is based on Siamese networks, measuring the distance between two samples in the feature space to determine whether they belong to the same malware family. The distance between the samples is gradually adjusted during the training of the model to improve the performance. A Malware Bazaar dataset analysis reveals that the proposed classification model has an accuracy and area under the curve (AUC) of 0.934 and 0.997, respectively. The proposed similarity model has an accuracy and AUC of 0.92 and 0.92, respectively. Further, the proposed similarity model identifies the unseen malware family with approximately 70% accuracy. Hence, the proposed similarity model exhibits better performance and scalability than the pure classification model and previous studies.

Oxysterol-binding protein 2 (OSBP2) is crucial for the promotion of growth and development of cancers, however, its effects in pancreatic ductal adenocarcinoma (PDAC) were still unclear. Here we report the evidence that OSBP2 works as an efficient tumor-associated protein to lead to PDAC extremely malignant characters. We discovered that raised OSBP2 expression in primary tumors was associated with shorter survival in PDAC patients. Therefore, we used immunohistochemistry to analysis the levels of OSBP2 expression in PDAC tissues and adjacent para-cancer tissues. We used wound-healing assay and transwell assay to evaluate the effects of OSBP2 on PDAC cells’ (ASPC-1 and BXPC-3) migration and invasion, respectively. Using CCK-8 and Annexin V / PI double staining, we evaluated the effects of OSBP2 on PDAC cells’ proliferation and apoptosis, respectively. We also explored the effect of OSBP2 on chemosensitivity (gemcitabine and 5-Fluorouracil). And we further validated these findings in vivo of mice. At last, we used western blot to analysis the effect of OSBP2 on PDAC cells’ phenotype. We proved that OSBP2 overexpression promoted PDAC cells’ migration, invasion, proliferation and chemotherapy resistance, decreased apoptosis. OSBP2 overexpression downregulated E-cadherin, and upregulated the levels of N-cadherin, vimentin, Snail, Slug, ZEB1 and β-Catenin. Taken collectively, our findings indicated that OSBP2 exhibited overexpression in PDAC, and upregulation of OSBP2 may promote the progression of PDAC. OSBP2 may have potential diagnostic and therapeutic values in PDAC.

Meteorological factors have been confirmed to affect the COVID-19 transmission, but current studied conclusions varied greatly. The underlying causes of the variance remain unclear. Here, we proposed two scientific questions: (1) whether meteorological factors have a consistent influence on virus transmission after combining all the data from the studies; (2) whether the impact of meteorological factors on the COVID-19 transmission can be influenced by season, geospatial scale and latitude. We employed a meta-analysis to address these two questions using results from 2813 published articles. Our results showed that, the influence of meteorological factors on the newly-confirmed COVID-19 cases varied greatly among existing studies, and no consistent conclusion can be drawn. After grouping outbreak time into cold and warm seasons, we found daily maximum and daily minimum temperatures have significant positive influences on the newly-confirmed COVID-19 cases in cold season, while significant negative influences in warm season. After dividing the scope of the outbreak into national and urban scales, relative humidity significantly inhibited the COVID-19 transmission at the national scale, but no effect on the urban scale. The negative impact of relative humidity, and the positive impacts of maximum temperatures and wind speed on the newly-confirmed COVID-19 cases increased with latitude. The relationship of maximum and minimum temperatures with the newly-confirmed COVID-19 cases were more susceptible to season, while relative humidity's relationship was more affected by latitude and geospatial scale. Our results suggested that relationship between meteorological factors and the COVID-19 transmission can be affected by season, geospatial scale and latitude. A rise in temperature would promote virus transmission in cold seasons. We suggested that the formulation and implementation of epidemic prevention and control should mainly refer to studies at the urban scale. The control measures should be developed according to local meteorological properties for individual city.

(1) Background: Strains HL1 and M1, isolated from kefir grains, have been tentatively identified, based on their partial 16S rRNA gene sequences, as Lactobacillus kefiranofaciens. The two strains demonstrated different health benefits. Therefore, not only the genetic factors exerting diverse functionalities in different L. kefiranofaciens strains, but also the potential niche-specific genes and pathways among the L. kefiranofaciens strains, should be identified. (2) Methods: Phenotypic and genotypic approaches were employed to identify strains HL1 and M1 at the subspecies level. For the further characterization of the probiotic properties of both strains, comparative genomic analyses were used. (3) Results: Both strains were identified as L. kefiranofaciens subsp. kefirgranum. According to the COG function category, dTDP-rhamnose and rhamnose-containing glycans were specifically detected in the L. kefiranofaciens subsp. Kefirgranum genomes. Three unique genes (epsI, epsJ, and epsK) encoding glycosyltransferase in the EPS gene cluster, and the ImpB/MucB/SamB family protein encoding gene were found in HL1 and M1. The specific ability to degrade arginine via the ADI pathway was found in HL1. The presence of the complete glycogen metabolism (glg) operon in the L. kefiranofaciens strains suggested the importance of glycogen synthesis to enable colonization in kefir grains and extend survival under environmental stresses. (4) Conclusions: The obtained novel information on the potential genes and pathways for polysaccharide synthesis and other functionalities in our HL1 and M1 strains could be applied for further functionality predictions for potential probiotic screening.

In hydrogen fuel cells, the sluggish oxygen reduction reaction (ORR) requires the catalysts used. Unfortunately, the precious platinum based catalysts still exhibit the best ORR activity in the commercial hydrogen fuel cells. Therefore, developing non-precious metal catalysts ORR become an important aspect for the utilization of hydrogen energy by using hydrogen fuel cells to develop non-precious catalysts and understand their active sites of ORR, herein the cobalt and nitrogen co-doped CNTs, nitrogen-doped CNTs and cobalt doped CNTs were prepared, respectively, and their catalytic properties toward ORR were tested and compared. The surface composition, microstructure and ORR performance of the samples were examined by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS), pore/specific surface analyzer and electrochemical methods. The results demonstrate that as the catalyst, the cobalt and nitrogen co-doped CNTs owns the highest ORR limiting current density, the most positive ORR onset potential and the largest transfer electron number close to four, and thus exhibits the better ORR catalytic performance compared to the other two samples of the nitrogen-doped CNTs and the cobalt doped CNTs. The good ORR performance of cobalt and nitrogen co-doped CNTs can be attributed to its active sites of nitrogen containing functional groups, cobalt or cobalt oxides, Co-Nx structure, and the synergistic effect of these sites on ORR.

Soil-structure interaction (SSI) is involved in the pile-supported structures. Such effect is mainly accounted for soil-pile interaction (SPI) driven by the deformation of pile and surround...

In the metabolic glycosylation grid of steviol glycosides, UGT76G1 was shown to catalyze at least eight different glucosylation steps, including the formation of rebaudioside B (Reb B) and rebaudioside A (Reb A) (Olsson et al., 2016). In this study, the accumulation of steviolbioside, Reb B, stevioside (ST) and Reb A in more than 140 samples of stevia leaves collected from different regions in China were analyzed by high-performance liquid chromatography (HPLC), and five genotypes, ‘N01-N05’, with significantly different levels of the abovementioned glycosides were discovered. Mutations in the UGT76G1 gene cloned from cDNAs from these five genotypes were identified, and the functions of the recombinant UGT76G1 variants were ascertained by adding steviolbioside and ST substrates. In addition, homology modeling and molecular docking were used to elucidate the functional differences between variants and UGT76G1. Comparing the sequences of the five variants ‘N01-N05’ with UGT76G1 (AY345974.1) revealed that base substitutions were not observed in ‘N01’. By contrast, ‘N02’ exhibited 9 single nucleotide polymorphisms (SNPs) and 9 associated amino acid substitutions or insertions with notable variations in the protein structure; however, an enzyme assay showed similar functionalities between the variant and UGT76G1. In ‘N03’, 49 SNPs and 29 associated amino acid substitutions or insertions were identified and shown to induce significant variations in the protein structure, especially in the binding pocket, resulting in the lack of functionality of this variant in the enzyme assay. These results were in agreement with the docking profiles. Moreover, a nonsense mutation of p.1090T > G in ‘N04’ and an insertion of a 68 base fragment in ‘N05’ were found, and both produced a premature protein without any catalytic activity. Therefore, UGT76G1, which is vital to the content of main steviol glycosides, should be a key gene marker for the molecular breeding of Stevia rebaudiana. Our investigations also revealed the location and orientation of active groups of the receptors and donors in the UGT76G1 enzyme, which play key roles in determining whether the enzyme has any enzymatic activity.