MWCNT Doped Reverse-Mode Polymer Network Liquid Crystals with Frequency Response Property

Polymer-liquid crystals(PLCs)are common materials for smart windows.However,PLC smart windows usually require high driving voltage to maintain transparency.We synthesized a novel PLC smart film by doping multi-wall carbon nanotubes(MWCNTs)into a reverse-mode polymer network liquid crystal(R-PNLC).

面向工程教育专业认证的有机化学实验微课混合式教学模式探索

根据化学工程与工艺专业的工程教育专业认证对有机化学实验课程提出的最新要求,从教学模式、教学内容、教师和学生四个方面详细分析了我校有机化学实验的教学现状及其存在问题。初步探索了一种适合本校实际情况的微课线上教学和传统线下教学相结合的混合式教学模式,并成功地应用于有机化学实验课程教学中,不仅可以有效提高实验课程教学的质量和效率,而且能够更好地支撑专业认证中课程教学目标和专业毕业要求。

Optical penetration of surface-enhanced micro-scale spatial offset Raman spectroscopy in turbid gel and biological tissue

The limited penetration of photons in biological tissue restricts the deep-tissue detection and imaging application.The micro-scale spatially offset Raman spectroscopy(micro-SORS)with an optical fiber probe,colleting photons from deeper regions by offsetting the position of laser excitation from the collection optics in a range of hundreds of microns,shows great potential to be integrated with endoscopy for inside-body noninvasive detection by circumventing this restric-tion,particularly with the combination of surface-enhanced Raman spectroscopy(SERS).However,a detailed tissue penetration study of micro-SORS in combination with SERS is still lacking.Herein,we compared the signal decay of enhanced Raman nanotags through the tissue phantom of agarose gel and the biological tissue of porcine muscle in the near-infrared(NIR)region using a portable Raman spectrometer with a micro-SORS probe(2.1 mm in diameter)and a conventional hand-held probe(9.7mm in diameter).Two kinds of Raman nanotags were prepared from gold nanorods decorated with the nonresonant(4-nitrobenzenethiol)or resonant Raman reporter molecules(IR-780 iodide).The SERS measurements show that the penetration depths of two Raman nanotags are both over 2 cm in agarose gel and 3 mm in porcine muscle.The depth could be improved to over 4 cm in agarose gel and 5 mm in porcine tissue when using the micro-SORS system.This demonstrates the superiority of optical-fiber micro-SORS system over the conventional Raman detection for the detection of nanotags in deeper layers in the turbid medium and biological tissue,offering the possibility of combining the micro-SORS technique with SERS for noninvasive in vivo endoscopy-integrated clinical application.

PET imaging for receptor occupancy: meditations on calculation and simplification

This invited mini-review briefly summarizes procedures and challenges of measuring receptor occupancy with positron emission tomography. Instead of describing the detailed analytic procedures of in vivo ligand-receptor imaging, the authors provide a pragmatic alJproach, along with personal perspectives, for conducting positron emission tomography imaging for receptor occupancy, and systematically elucidate the mathematics of receptor occupancy calculations in practical ways that can be understood with elementary algebra. The authors also share insights regarding positron emission tomography imaging for receptor occupancy to facilitate applications for the development of drugs targeting receptors in the central nervous system.

Detection of the synoptic southeastward-extending Siberian cold high during 1978-2017

To better understand the relationship between anticyclones in Siberia and cold-air activities and temperature changes in East Asia,this study proposes a 2D anticyclone identification method based on a deep-learning model,Mask R-CNN,which can reliably detect the changes in the morphological characteristics of anticyclones.Using the new method,the authors identified the southeastward-extending Siberian cold high(SEESCH),which greatly affects wintertime temperatures in China.This type of cold high is one of the main synoptic systems(45.7%)emerging from Siberia in winter.Cold air carried by SEESCH has a significant negative correlation with the temperature changes in the downstream area,and 52% of SEESCHs are accompanied by cold-air accumulation in North and East China,which has a significant impact on regional cooling.These results provide clues for studying the interconnection between SEESCHs and extreme cold events.

Raw Ginger Composite Antioxidant with High Efficiency to Extract Vitamin C from Strawberry

Raw ginger was introduced to a series of composite antioxidants. The specimens performed better efficiency than ordinary antioxidants while extracting vitamin C from strawberry. The results suggested that, by employing raw ginger composite antioxidant, the reservation of vitamin C could be 91.63% in washing process and 76.68% in squeezing process respectively. Furthermore, in squeezing process, the reservation of vitamin C reached 84.78% while the concentrate of raw ginger antioxidant was 0.03%. The both deposits performed perfect synergy effectively. Raw ginger composite antioxidant could be the well agent to extract vitamin C from fruit.

Structure-based design of pan-coronavirus inhibitors targeting host cathepsin L and calpain-1

Respiratory disease caused by coronavirus infection remains a global health crisis.Although several SARS-CoV-2-specific vaccines and direct-acting antivirals are available,their effcacy on emerging coronaviruses in the future,including SARS-CoV-2 variants,might be compromised.Host-targeting antivirals provide preventive and therapeutic strategies to overcome resistance and manage future outbreak of emerging coronaviruses.Cathepsin L(CTSL)and calpain-1(CAPN1)are host cysteine proteases which play crucial roles in coronaviral entrance into cells and infection-related immune response.Here,two peptidomimetic a-ketoamide compounds,14a and 14b,were identified as potent dual target inhibitors against CTSL and CAPN1.The X-ray crystal structures of human CTSL and CAPN1 in complex with 14a and 14b revealed the covalent binding of a-ketoamide groups of 14a and 14b to C25 of CTSL and C115 of CAPN1.Both showed potent and broad-spectrum anticoronaviral activities in vitro,and it is worth noting that they exhibited low nanomolar potency against SARS-CoV-2 and its variants of concern(VOCs)with ECso values ranging from 0.80 to 161.7 nM in various cells.Preliminary mechanistic exploration indicated that they exhibited anticoronaviral activity through blocking viral entrance.Moreover,14a and 14b exhibited good oral pharmacokinetic properties in mice,rats and dogs,and favorable safety in mice.In addition,both 14a and 14b treatments demonstrated potent antiviral potency against SARS-CoV-2 XBB 1.16 variant infection in a K18-hACE2 transgenic mouse model.And 14b also showed effective antiviral activity against HCoV-OC43 infection in a mouse model with a final survival rate of 60%.Further evaluation showed that 14a and 14b exhibited excellent antiinflammatory effects in Raw 264.7 mouse macrophages and in mice with acute pneumonia.Taken together,these results suggested that 14a and 14b are promising drug candidates,providing novel insight into developing pan-coronavirus inhibitors with antiviral and anti-inflammatory properties.

Discovery and characterization of novel potent non-covalent small molecule inhibitors targeting papain-like protease from SARS-CoV-2

To the Editor:The papain-like protease(PL^(pro)),as one of the most important proteases of SARS-CoV-2,has emerged as a highly promising target protein,its inhibitor probably holds dual potentials,namely blocking the cleavage of viral polyprotein and intercepting the deubiquitination and deISGylation functions to restore antiviral immunity1.

Design of antiviral AGO2-dependent short hairpin RNAs

The increasing emergence and re-emergence of RNA virus outbreaks underlines the urgent need to develop effective antivirals.RNA interference(RNAi)is a sequence-specific gene silencing mechanism that is triggered by small interfering RNAs(siRNAs)or short hairpin RNAs(shRNAs),which exhibits significant promise for antiviral therapy.AGO2-dependent shRNA(agshRNA)generates a single-stranded guide RNA and presents significant advantages over traditional siRNA and shRNA.In this study,we applied a logistic regression algorithm to a previously published chemically siRNA efficacy dataset and built a machine learning-based model with high predictive power.Using this model,we designed siRNA sequences targeting diverse RNA viruses,including human enterovirus A71(EV71),Zika virus(ZIKV),dengue virus 2(DENV2),mouse hepatitis virus(MHV)and severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),and transformed them into agshRNAs.We validated the performance of our agshRNA design by evaluating antiviral efficacies of agshRNAs in cells infected with different viruses.Using the agshRNA targeting EV71 as an example,we showed that the anti-EV71 effect of agshRNA was more potent compared with the corresponding siRNA and shRNA.Moreover,the antiviral effect of agshRNA is dependent on AGO2-processed guide RNA,which can load into the RNA-induced silencing complex(RISC).We also confirmed the antiviral effect of agshRNA in vivo.Together,this work develops a novel antiviral strategy that combines machine learning-based algorithm with agshRNA design to custom design antiviral agshRNAs with high efficiency.

链球菌引发宿主中毒性休克综合症相关机制的研究进展

某些链球菌在感染过程中,会引发宿主系统性的细胞因子风暴,病程进展迅速,致死率高,即发生链球菌性中毒性休克综合症(streptococcal toxic shock syndrome,STSS)。最初认为STSS由链球菌的超抗原(superantigen,SAg)引发,但近年来也有不依赖超抗原的STSS病例报道,致病机制较为复杂。本文主要对不依赖链球菌超抗原引发STSS的机制研究进行介绍,包括链球菌感染后宿主细胞中炎症信号通路的激活、炎性小体和细胞焦亡的发生、促炎细胞因子的释放以及细胞因子风暴等。同时,对研究链球菌STSS常采用的细胞和动物模型进行总结,旨在为实验室开展STSS的机制研究奠定理论基础。

一例迟发诊断22q11.2缺失综合征合并卵巢混合性生殖细胞瘤

特发性甲状旁腺功能减退症是一种罕见的内分泌疾病,常表现为神经精神症状,尤其是癫痫发作,因此在临床上容易被误诊为原发性癫痫。本文报道了1例长期被误诊断为原发性癫痫的17岁女性患者,因行卵巢混合性生殖细胞瘤手术期间发现甲状旁腺功能减退而就诊,经全外显子测序后明确诊断为22q11.2缺失综合征。本病例提示临床医师应关注青少年癫痫中甲状旁腺功能减退症的可能,尤其要考虑到遗传性甲状旁腺功能减退症的可能;与此同时,关注甲状旁腺以外的异常症状和体征,尤其是肿瘤的风险。

Regulation of Seed Vigor by Manipulation of Raffinose Family Oligosaccharides in Maize and Arabidopsis thaliana

Raffinose family oligosaccharides （RFOs） accumulate in seeds during maturation desiccation in many plant species. However, it remains unclear whether RFOs have a role in establishing seed vigor. GALACTINOL SYNTHASE （GOLS）, RAFFINOSE SYNTHASE （RS）, and STACHYOSE SYNTHASE （STS） are the enzymes responsible for RFO biosynthesis in plants. Interestingly, only raffinose is detected in maize seeds, and a unique maize RS gene （ZmRS） was identified. In this study, we found that two independent mutator （Mu）-interrupted zmrs lines, containing no raffinose but hyperaccumulating galactinol, have significantly reduced seed vigor, compared with null segregant controls. Unlike maize, Arabidopsis thaliana seeds contain several RFOs （raffinose, stachyose, and verbascose）. Manipulation of A. thaliana RFO content by overexpressing ZmGOLS2, ZmRS, or AtSTS demonstrated that co-overexpression of ZmGOLS2 and ZmRS, or overexpression of ZmGOLS2 alone, significantly increased the total content of RFOs and enhanced Arabidopsis seed vigor. Surprisingly, while overexpression of ZmRS increased seed raffinose content, its overexpression dramatically decreased seed vigor and reduced the seed amounts of galactinol, stachyose, and verbascose. In contrast, the atrs5 mutant seeds are similar to those of the wild type with regard to seed vigor and RFO content, except for stachyose, which accumulated in atrs5 seeds. Total RFOs, RFO/sucrose ratio, but not absolute individual RFO amounts, positively correlated with A. thaliana seed vigor, to which stachyose and verbascose contribute more than raffinose. Taken together, these re- sults provide new insights into regulatory mechanisms of seed vigor and reveal distinct requirement for RFOs in modulating seed vigor in a monocot and a dicot.

Injectable dual glucose-responsive hydrogel-micelle composite for mimicking physiological basal and prandial insulin delivery

For type 1 and advanced type 2 diabetic patients, insulin replacement therapy with simulating on-demand prandial and basal insulin secretion is the best option for optimal glycemic control. However, there is no insulin delivery system yet could mimic both controlled basal insulin release and rapid prandial insulin release in response to real-time blood glucose changes. Here we reported an artificial insulin delivery system, mimicking physiological basal and prandial insulin secretion, to achieve real-time glycemic control and reduce risk of hypoglycemia. A phenylboronic acid(PBA)/galactosyl-based glucose-responsive insulin delivery system was prepared with insulin-loaded micelles embedded in hydrogel matrix. At the hyperglycemic state, both the hydrogel and micelles could swell and achieve rapid glucose-responsive release of insulin, mimicking prandial insulin secretion.When the glucose level returned to the normal state, only the micelles partially responded to glucose and still released insulin gradually. The hydrogel with increased crosslinking density could slow down the diffusion speed of insulin inside, resulting in controlled release of insulin and simulating physiological basal insulin secretion. This hydrogel-micelle composite insulin delivery system could quickly reduce the blood glucose level in a mouse model of type 1 diabetes, and maintain normal blood glucose level without hypoglycemia for about 24 h. This kind of glucose-responsive hydrogel-micelle composite may be a promising candidate for delivery of insulin in the treatment of diabetes.

Polarization of tumor-associated macrophages by TLR7/8 conjugated radiosensitive peptide hydrogel for overcoming tumor radioresistance

Radioresistance reduces the antitumor efficiency of radiotherapy and further restricts its clinical application,which is mainly caused by the aggravation of immunosuppressive tumor microenvironment(ITM).Especially tumor-associated macrophages(TAMs)usually display the tumor-promoting M2 phenotype during high-dose fractional radiotherapy mediating radiotherapy resistance.Herein,the toll like receptor agonist TLR7/8a was conjugated with radiosensitive peptide hydrogel(Smac-TLR7/8 hydrogel)to regulate TAMs repolarization from M2 type into M1 type,thus modulating the ITM and overcoming the radioresistance.The Smac-TLR7/8 hydrogel was fabricated through self-assembly with nanofibrous morphology,porous structure and excellent biocompatibility.Uponγ-ray radiation,Smac-TLR7/8 hydrogel effectively polarized the macrophages into M1 type.Notably,combined with radiotherapy,TAMs repolarization regulated by Smac-TLR7/8 hydrogel could increase tumor necrosis factor secretion,activate antitumor immune response and effectively inhibit tumor growth.Moreover,TAMs repolarization rebuilt the ITM and elicited the immunogenic phenotypes in solid tumors,thus enhanced the PD1-blockade efficacy through increasing tumor infiltrating lymphocytes(TILs)and decreasing Treg cells in two different immune activity tumor mice models.Overall,this study substantiated that recruiting and repolarization of TAMs were critical in eliciting antitumor immune response and overcoming radioresistance,thus improving the efficacy of radiotherapy and immunotherapy.

Graphene-like two-dimensional nanosheets-based anticorrosive coatings: A review

In recent years, graphene has been widely employed in the field of metal corrosion protection owing to its outstanding impermeability and chemical stability, with examples of such metal protection including pure graphene coatings and graphene-based composite coatings. But the conductive graphene could promote the electrochemical reaction at the interface and accelerate the corrosion of metal substrates. More emerging graphene-like 2D nanosheets are attracting research attention for the application of metal anticorrosion, because of their barrier properties and poor conductivity, mainly including boron nitride(BN),molybdenum disulfide(MoS_(2)), zirconium phosphate(ZrP), and titanium carbide(MXene). In this review,the application of these graphene-like 2D nanosheets to metal protection is comprehensively reviewed.First, the general preparation methods of 2D nanosheets are briefly introduced. Second, surface functionalization of 2D nanosheets, including covalent and non-covalent modification, is described in detail.Third, the anticorrosion performance and optimization measures of pure 2D nanosheets coatings are summarized. Next, the protection performance, anticorrosive mechanism, and optimizations of 2D nanosheets composite coatings are presented. Finally, the future development of 2D nanosheets-based anticorrosive coatings has been prospected, and the challenges in the industrial application are discussed.

Integrated generation–consumption dispatch based on compensation mechanism considering demand response behavior

Demand response(DR) is important to account for behaviors of the demand side to yield an optimal dispatch result. However, it is difficult for energy suppliers to collect customers' private information unless there is an incentive mechanism for customers to do so. Therefore,this paper proposes a new integrated generation–consumption dispatch based on compensation mechanism considering DR behavior. Firstly, in light of the dayahead load forecast data, we deduce the utility function model of different customers. By subtracting generating units' operation cost from consumers' total utility, the dispatch model has a decentralized demand participant structure based on this utility function. The utility function is used to describe consumers' preferences and energy consumption behaviors. Secondly, an effective compensation mechanism is designed to ensure customers to select the level of compensation appropriate to their willingness to curtail load. Finally, a new dispatch model is proposed that incorporates the DR compensation mechanism into the generation–consumption dispatch model. The new model can improve the interaction of generation and consumption,and benefit both the energy supplier and its customers. The proposed model is piecewise linearized and solved by a mixed-integer linear programming method. It is tested on a six-bus system and the IEEE 118-bus system. Simulation results show that the proposed model can realize both maximum social welfare and Pareto optimal results.

Evolution of microstructures and optical properties of gadolinium oxide with oxygen flow rate and annealing temperature

In this study, the effects of oxygen flow rate and annealing temperature on Gd_2 O_3 structures and optical properties were systematically analyzed. Gd_2 O_3 films were deposited on both quartz and ZnS substrates by magnetron sputtering and then annealed under vacuum at 700, 800 and 900℃, Restructure and phase transformation from cubic to monoclinic occur at different temperatures depending on the oxygen flow rate. The optical band gap, which is more sensitive to the annealing temperature than oxygen flow rate changes from 5.32 to 5.65 eV. The refractive index is approximately 1.75 at 550 nm and is adjustable by the oxygen flow rate. The transmittance of the ZnS substrate with Gd_2 O_3 film exceeds 80% and reaches82% at the 7.5-9.5 μm range. When ZnS is coated on both sides, the transmittance is increased to approximately 90%. Our results indicate that Gd_2 O_3 films are promising new candidates for anti-reflective coatings in the infrared region.

Oral remdesivir derivative VV116 is a potent inhibitor of respiratory syncytial virus with efficacy in mouse model

Dear Editor,Respiratory syncytial virus(RSV)is the leading cause of serious lower respiratory tract disease in children under 5 years of age worldwide,causing an estimated 3.2 million hospitalizations and 120,000 deaths in children globally per year.Furthermore,nearly all children can be infected with RSV by 2 years of age,and individuals can be repeatedly re-infected with RSV throughout life,which poses great threats to infants,the elderly.

A viral RNA-dependent RNA polymerase inhibitor VV116 broadly inhibits human coronaviruses and has synergistic potency with 3CLpro inhibitor nirmatrelvir

During the ongoing pandemic,providing treatment consisting of effective,low-cost oral antiviral drugs at an early stage of SARSCoV-2 infection has been a priority for controling COVID-19.Although Paxlovid and molnupiravir have received emergency approval from the FDA,some side effect concerns have emerged,and the possible oral agents are stillimited,resulting in optimized drug development becoming an urgent requirement.

A multi-objective antidisturbance robust filter for SINS/GPS navigation systems

Purpose-A full-order multi-objective anti-disturbance robust filter for SINS/GPS navigation systems with multiple disturbances is designed.Generally,the unmodeled dynamics,the external environmental disturbance and the inertial apparatus random drift may exist simultaneously in an integrated navigation system,which can be classified into three type of disturbances,that is,the Gaussian noise,the norm bounded noise and the time correlated noise.In most classical studies,the disturbances in integrated navigation systems are classified as Gaussian noises or norm bounded noises,where the Kalman filtering or robust filtering can be employed,respectively.While it is not true actually,such assumptions may lead to conservative results.The paper aims to discuss these issues.Design/methodology/approach-The Gaussian noises,the norm bounded noises and the time correlated noises in the integrated navigation system are considered simultaneously in this contribution.As a result,the time correlated noises are augmented as a part of system state of the integrated navigation system error model,the relative integrated navigation problem can be transformed into a full-order multi-objective robust filter design problem for systems with Gaussian noises and norm bounded disturbances.Certainly,the errors of the time correlated noises are estimated and compensated for high precision navigation purpose.Sufficient conditions for the existence of the proposed filter are presented in terms of linear matrix inequalities(LMIs)such that the system stability is guaranteed and the disturbance attenuation performance is achieved.Findings-Simulations for SINS/GPS integrated navigation system given show that the proposed full-order multi-objective anti-disturbance filter,has stronger robustness and better precision when multiple disturbances exist,that is,the present algorithm not only can suppression the effect of white noises and norm bounded disturbance but also can estimate and compensate the modeled disturbance.Originality/value-The proposed algorithm has stronger anti-disturbance ability for integrated navigation with multiple disturbances.In fact,there exist multiple disturbances in integrated navigation system,so the proposed scheme has important significance in applications.