Machine learning models for stroke detection by observing the eye-movement features under five-color visual stimuli in traditional Chinese medicine

Objective:To develop a novel diagnostic modality to identify and diagnose stroke in daily life scenarios for improving the therapeutic effects and prognoses of patients.Methods:In this study,16 stroke patients and 24 age-matched healthy participants as controls were recruited for comparative analysis.Leveraging a portable eye-tracking device and integrating traditional Chinese medicine theory with modern color psychology principles,we recorded the eye movement signals and calculated eye movement features.Meanwhile,the stroke recognition models based on eye movement features were further trained by using random forest(RF),k-nearest neighbors(KNN),decision tree(DT),gradient boosting classifier(GBC),XGBoost,and CatBoost.Results:The stroke group and the healthy group showed significant differences in some eye movement features(P<.05).The models trained based on eye movement characteristics had good performances in recognizing stroke individuals,with accuracies ranging from 77.40%to 88.45%.Under the red stimulus,the eye movement model trained by RF became the best machine learning model with a recall of 84.65%,a precision of 86.48%,a F1 score of 85.47%.Among the six algorithms,RF and CatBoost performed better in classification.Conclusion:This study pioneers the application of traditional Chinese medicine's five-color stimuli to visual observation tasks.On the basis of the combined design,the eye-movement models can accurately identify stroke,and the developed high-performance models may be used in daily life scenarios.

Fiber-Loop Ringdown Multi-Function Sensors

We demonstrate a fiber-loop ring down multi-function sensors system, which can be used to measure refractive index and curvature simultaneously. Good agreement has been found between theoretical analyses and experimental results. It has great potential for sensor applications.

5 kW-level single-mode fiber amplifier based on low-numerical-aperture fiber

A low-numerical-aperture(NA)concept enables large-mode-area fiber with better single-mode operation ability,which is beneficial for transverse mode instability and nonlinear effects suppression.In this contribution,we reported a high-power fiber amplifier based on a piece of self-developed large-mode-area low-NA fiber with a core NA of 0.049 and a core/inner cladding diameter of 25/400μm.The influence of the pump wavelength and fiber length on the power scaling potential of the fiber amplifier is systematically investigated.As a result,an output of 4.80 kW and a beam quality factor of~1.33 were finally obtained,which is the highest output power ever reported in a fiber amplifier exploiting the low-NA fiber.The results reveal that low-NA fibers have superiority in power scaling and beam quality maintenance at high power levels.

Multifunctional polyeugenol-based nanoparticles with antioxidant and antibacterial properties

Over the past few decades,extensive scientific has been dedicated to polymer synthesis employing renewable resources.In this study,we devised and synthesized multifunctional polyeugenol-based nanoparticles,exhibiting remarkable antioxidant and antibacterial properties.The grafting of eugenol onto the nanoparticle surface was achieved via a thiol-ene chemical reaction with a grafting rate of 3.5%.To comprehend the properties of the synthesized nanoparticles,we employed Fourier transform infrared spectroscopy,X-ray photoelectron spectroscopy and pyrolysis-gas chromatography mass spectrometry.Subsequent scanning electron microscopic and transmission electron microscopic analyses revealed the presence of a crosslinked structure within the polyeugenol-based nanoparticles,as well as a heteroge-neous microsphere structure on the surface.Due to the inherent crosslinking structure,the polyeugenol-based nanoparticles demonstrated robust the resistance to solvents,as ascertained through thermog-ravimetric analysis and solvent resistance tests.Notably,nitrogen adsorption/desorption studies confirmed the adsorption capacity of the polyeugenol-based nanoparticles,rendering them potentially suitable for drug transport applications.Moreover,the assays for assessing cytocompatibility and reactive oxygen species scavenging activities demonstrated better performance of the eugenol-based nano-particles compared to eugenol.Furthermore,the polyeugenol-based nanoparticles exhibited certain bactericidal activities against Escherichia coli,Staphylococcus aureus,and Fusobacterium nucleatum.Consequently,these observations indicated the nontoxic nature and expansive application prospects of the polyeugenol-based nanoparticles in the domains of medicine and food preservation.This work presented a pioneering concept for the development of antioxidant and antibacterial multifunctional polymer materials derived from eugenol.

2×3 kW bidirectional output fiber oscillator employing spindle-shaped ytterbium-doped fiber

A 2×3 kW-level bidirectional output fiber oscillator is realized by combining the specially designed spindle-shaped ytterbium-doped fiber,non-wavelength-stabilized 976-nm LDs,and grating bandwidth optimization to balance transverse mode instability and stimulated Raman scattering.The maximum output powers at both ends are 3265 and 2840 W,respectively,with a total efficiency of 73.2%.The M^(2) factors of the lasers at both ends are about 1.98 and 2.38,respectively.The beam profile at both ends shows that a bidirectional output annular beam fiber oscillator has been realized,which has great potential in practical applications.

Fiber oscillator of 5 kW using fiber Bragg gratings inscribed by a visible femtosecond laser

We fabricate a pair of fiber Bragg gratings(FBGs)by a visible femtosecond laser phase mask scanning technique on passive large-mode-area double-cladding fibers for multi-kilowatt fiber oscillators.The bandwidth of high-reflection(HR)and lowreflection(LR)FBG is~1.6 nm and 0.3 nm,respectively.The reflection of the HR-FBG is higher than 99%,and that of the LR-FBG is about 10%.A bidirectional pumped all-fiber oscillator is constructed using this pair of FBGs,a record output power of 5027 W located in the signal core is achieved with a slope efficiency of~82.1%,and the beam quality factor M2is measured to be~1.6 at the maximum power.The FBGs are simply fixed on a water cooling plate without a special package,and the thermal efficiency of the HR-FBG and the LR-FBG is 2.76℃/kW and 1℃/kW,respectively.Our research provides an effective solution for robust high-power all-fiber laser oscillators.

术前预康复对全膝关节置换术后早期功能恢复效果的影响

目的探讨在加速康复外科多学科协作模式下术前预康复对膝关节置换术后早期功能恢复效果的影响。方法回顾性分析2019年9月至2021年12月在晋江市医院骨科接受全膝关节置换术患者51例的临床资料,将51例患者中按术前是否采用术前预康复分为观察组(24例)和对照组(27例),在行膝关节置换术前进行预康复的设为观察组,术前未进行预康复的设为对照组。观察组在办理入院手续后,前往康复门诊进行康复评估,并在同一个康复师指导下行个性化康复训练,后续手术后康复师跟进术后康复。对照组则无术前预康复,术后康复师及时介入康复,康复师在术后2 d和5 d分别对患者进行康复评分(HSS评分、运动疼痛目测类比评分等)。主要观察指标:患者术后2 d、5 d膝关节活动度(range of motion,ROM);术后2 d、5 d膝关节功能评价表(hospital for special surgery knee score,HSS);术后5 d运动疼痛目测类比评分(visual analogous scale,VAS);术后至出院天数;术后并发症发生率;术后康复科门诊回访情况等。结果观察组与对照组术后2 d ROM评分差异无统计学意义(P>0.05),两组术后5 d ROM评分差异有统计学意义[(100.08±7.75)分比(88.44±16.09)分,t=3.34,P=0.002];术后2 d两组HSS评分差异无统计学意义(P>0.05),术后5 d两组HSS评分差异有统计学意义[(62.84±5.78)分比(57.09±6.53)分,t=3.31,P=0.002];术后5 d两组VAS(运动时)评分差异有统计学意义[(3.42±1.02)分比(5.37±1.15)分,t=-6.39,P<0.001];两组术后至出院天数差异无统计学意义(P>0.05)。术后并发症发生率差异无统计学意义(P>0.05),两组术后康复科门诊回访情况差异有统计学意义[(7/17)比(1/26),χ^(2)=4.45,P=0.035]。结论加速康复外科多学科协作模式下术前预康复有助于提高全膝关节置换术患者的早期功能水平,降低术后康复疼痛感,提高患者术后康复依从性,提升患者对手术的满意度。

mRNA therapeutics:New vaccination and beyond

The idea of mRNA therapy had been conceived for decades before it came into reality during the Covid-19 pandemic.The mRNA vaccine emerges as a powerful and general tool against new viral infections,largely due to its versatility and rapid development.In addition to prophylactic vaccines,mRNA technology also offers great promise for new applications as a versatile drug modality.However,realizing the conceptual potential faces considerable challenges,such as minimal immune stimulation,high and long-term expression,and efficient delivery to target cells and tissues.Here we review the applications of mRNA-based therapeutics,with emphasis on the innovative design and future challenges/solutions.In addition,we also discuss the next generation of mRNA therapy,including circular mRNA and self-amplifying RNAs.We aim to provide a conceptual overview and outlook on mRNA therapeutics beyond prophylactic vaccines.

Phase-separated bienzyme compartmentalization as artificial intracellular membraneless organelles for cell repair

Implanting artificial organelles in living cells is capable of correcting cellular dysfunctionalities for cell repair and biomedical applications. In this work, phase-separated bienzyme-loaded coacervate microdroplets are established as a model of artificial membraneless organelles in endothelial dysfunctional cells for the cascade enzymatic production of nitric oxide(NO) with a purpose of correcting cellular NO deficiency. We prepared the coacervate microdroplets via liquid-liquid phase separation of oppositely charged polyelectrolytes, in which glucose oxidase/horseradish peroxidase-mediated cascade reaction was compartmented. After the coacervate microdroplets were implanted in NO-deficient dysfunctional cells, the compartments maintained a phase-separated liquid droplet structure, which facilitated a significant enhancement of NO production in the dysfunctional cells. The recovery of NO production was further exploited to inhibit clot formation in blood plasma located in the cell suspension. This demonstrated a proof-of-concept design of artificial organelles in dysfunctional cells for cell repair and anticoagulation-related medical applications. Our results demonstrate an approach for the construction of coacervate droplets through phase separation for the generation of artificial membraneless organelles, which can be designed to provide an array of functionalities in living organisms that have the potential to be used in the field of cell engineering and medical therapy.

A 110 W fiber gas Raman laser at 1153 nm

We report here the first hundred-watt continuous wave fiber gas laser in H_(2)-filled hollow-core photonic crystal fiber(PCF)by stimulated Raman scattering.The pump source is a homemade narrow-linewidth fiber oscillator with a 3 dB linewidth of 0.15 nm at the maximum output power of 380 W.To efficiently and stably couple several-hundred-watt pump power into the hollow core and seal the gas,a hollow-core fiber end-cap is fabricated and used at the input end.A maximum power of 110 W at 1153 nm is obtained in a 5 m long hollow-core PCF filled with 36 bar H2,and the conversion efficiency of the first Stokes power is around 48.9%.This work paves the way for high-power fiber gas Raman lasers.

Targeting dysregulated splicing factors in cancer:lessons learned from RBM10 deficiency

Ribonucleic acid(RNA)splicing dysregulation is considered a molecular hallmark and important therapeutic target of cancer.Although targeting splicing has been intensively pursued for cancer therapy,specific modulators of dysregulated splicing factors are generally lacking.RNA binding motif protein 10(RBM10)is frequently mutated in multiple cancers,in particular lung adenocarcinoma(LUAD).Increasing evidence has demonstrated that RBM10 deficiency due to loss-of-function(LOF)mutation or aberrant expression contributes to cancer development,progression,and therapeutic response.Here,we summarize the functional consequences and new therapeutic implications of RBM10 deficiency in cancer.Using RBM10 as a representative example,we highlight main strategies for targeting dysregulated splicing factors.These strategies,either alone or in combination with currently approved therapies,may hold great promise in cancer treatment.

IDeAS:an interactive database for dysregulated alternative splicing in cancers across Chinese and western patients

Splicing of pre-RNA is a key step in regulating eukaryotic gene expression.Most human genes undergo alternative splicing(AS),where the splice sites in a single gene can be selectively paired to produce multiple isoforms,greatly expanding the functional diversity(Pan et al.,2008;Wang et al.,2008).The regulation of AS plays a critical role in many cellular activities,such as cell differentiation.Therefore,the dysregulation of AS can lead to a variety of diseases,including cancers(Scotti and Swanson,2016).

人造细胞的化学构建及其生物医学应用研究

人造细胞是模拟生物细胞结构,人工构建的与细胞功能相近的微米囊泡。人造细胞的构建主要有两种模式:自上而下模式主要利用生物学方法对生物基因序列进行重新设计,获得具有细胞类似结构功能的人造细胞;自下而上模式主要利用化学方法采用非生命物质构筑简化的细胞结构模型。自下而上化学模式构建的人造细胞大多只包含执行所需功能的最小单元,具有简单的细胞仿生的结构与功能。本文详细综述了人造细胞的构建模式以及化学构建人造细胞的常见类型,包括脂质囊泡、蛋白体囊泡、聚合物囊泡、凝集体液滴和胶体囊泡等,总结了人造细胞在分析传感、细胞结构与功能模拟、生物载体转运、微纳米反应器、疾病诊疗方面的生物医学应用现状。

IRES-mediated cap-independent translation,a path leading to hidden proteome

Most eukaryotic mRNAs are translated in a cap-dependent fashion;however,under stress conditions,the cap-independent translation driven by internal ribosomal entry sites(IRESs)can serve as an alternative mechanism for protein production.Many IRESs have been discovered from viral or cellular mRNAs to promote ribosome assembly and initiate translation by recruiting different trons-acting factors.Although the mechanisms of translation initiation driven by viral IRESs are relatively well understood,the existence of cellular IRESs is still under debate due to the limitations of translation reporter systems used to assay IRES activities.A recent screen identified>1000 putative IRESs from viral and human mRNAs,expanding the scope and mechanism for capindependent translation.Additionally,a large number of circular RNAs lacking free ends were identified in eukaryotic cells,many of which are found to be translated through IRESs.These findings suggest that IRESs may play a previously unappreciated role in driving translation of the new type of mRNA,implying a hidden proteome produced from cap-independent translation.

Mitigation of stimulated Raman scattering in kilowatt-level diode-pumped fiber amplifiers with chirped and tilted fiber Bragg gratings

The average power of diode-pumped fiber lasers has been developed deeply into the kW regime in the past years.However, stimulated Raman scattering(SRS) is still a major factor limiting the further power scaling. Here, we have demonstrated the mitigation of SRS in kilowatt-level diode-pumped fiber amplifiers using a chirped and tilted fiber Bragg grating(CTFBG) for the first time. The CTFBG is designed and inscribed in large-mode-area(LMA) fibers, matching with the operating wavelength of the fiber amplifier. With the CTFBG inserted between the seed laser and the amplifier stage, an SRS suppression ratio of ~10 dB is achieved in spectrum at the maximum output laser power of 2.35 kW,and there is no reduction in laser slope efficiency and degradation in beam quality. This work proves the feasibility and practicability of CTFBGs for SRS suppression in high-power fiber lasers, which is very useful for the further power scaling.

Effective suppression of stimulated Raman scattering in half 10 kW tandem pumping fiber lasers using chirped and tilted fiber Bragg gratings

The average power of fiber lasers has been scaled deeply into the kW regime in the past years. However, stimulated Raman scattering(SRS) is still a major factor limiting further power scaling. Here, we have demonstrated for the first time, to the best of our knowledge, the suppression of SRS in a half 10 kW tandem pumping fiber amplifier using chirped and tilted fiber Bragg gratings(CTFBGs). With specially self-designed and manufactured CTFBGs inserted between the seed laser and the amplifier stage, a maximum SRS suppression ratio of >15 dB in spectrum is observed with no reduction in laser efficiency. With one CTFBG, the effective output power is improved to3.9 kW with a beam quality M2 factor of ～1.7 from <3.5 k W with an M2 factor of >2; with two CTFBGs, the effective laser power reaches 4.2 kW with an increasing ratio of 20% and an M2 factor of ～1.8, and further power improvement is limited by the power and performance of the 1018 nm pump sources. This work provides an effective SRS suppression method for high-power all-fiber lasers, which is useful for further power scaling of these systems.

Splicing dysregulation in cancer: from mechanistic understanding to a new class of therapeutic targets

RNA splicing dysregulation is widespread in cancer. Accumulating evidence demonstrates that splicing defects resulting from splicing dysregulation play critical roles in cancer pathogenesis and can serve as new biomarkers and therapeutic targets for cancer intervention. These findings have greatly deepened the mechanistic understandings of the regulation of alternative splicing in cancer cells, leading to rapidly growing interests in targeting cancer-related splicing defects as new therapies. Here we summarize the current research progress on splicing dysregulation in cancer and highlight the strategies available or under development for targeting RNA splicing defects in cancer.

Towards all-fiber structure pulsed mid-infrared laser by gas-filled hollow-core fibers

We report here on a diode-pumped pulsed mid-infrared laser source based on gas-filled hollow-core fibers(HCFs)towards an all-fiber structure by the tapering method. The pump laser is coupled into an acetylene-filled HCF through a tapered single-mode fiber. By precisely tuning the wavelength of the diode to match different absorption lines of acetylene near 1.5 μm, mid-infrared emission around 3.1–3.2 μm is generated. With 2 m HCFs and3 mbar acetylene gas, a maximum average power of 130 m W is obtained with a laser slope efficiency of ~24%.This work provides a potential scheme for all-fiber mid-infrared fiber gas lasers.

A systematic survey of PRMT interactomes reveals the key roles of arginine methylation in the global control of RNA splicing and translation

Thousands of proteins undergo arginine methylation,a widespread post-translational modification catalyzed by several protein arginine methyltransferases(PRMTs).However,global understanding of their biological functions is limited due to the lack of a complete picture of the catalytic network for each PRMT.Here,we systematically identified interacting proteins for all human PRMTs and demonstrated their functional importance in mRNA splicing and translation.We demonstrated significant overlapping of interactomes of human PRMTs with the known methylarginine-containing proteins.Different PRMTs are functionally redundant with a high degree of overlap in their substrates and high similarities between their putative methylation motifs.Importantly,RNA-binding proteins involved in regulating RNA splicing and translation contain highly enriched arginine methylation regions.Moreover,inhibition of PRMTs globally alternates alternative splicing(AS)and suppresses translation.In particular,ribosomal proteins are extensively modified with methylarginine,and mutations in their methylation sites suppress ribosome assembly,translation,and eventually cell growth.Collectively,our study provides a global view of different PRMT networks and uncovers critical functions of arginine methylation in regulating mRNA splicing and translation.

Towards high-power mid-IR light source tunable from 3.8 to 4.5 µm by HBr-filled hollow-core silica fibres

Fibre lasers operating at the mid-IR have attracted enormous interest due to the plethora of applications in defence,security,medicine,and so on.However,no continuous-wave(CW)fibre lasers beyond 4μm based on rare-earth-doped fibres have been demonstrated thus far.Here,we report efficient mid-IR laser emission from HBr-filled silica hollow-core fibres(HCFs)for the first time.By pumping with a self-developed thulium-doped fibre amplifier seeded by several diode lasers over the range of 1940–1983 nm,narrow linewidth mid-IR emission from 3810 to 4496 nm has been achieved with a maximum laser power of about 500 mW and a slope efficiency of approximately 18%.To the best of our knowledge,the wavelength of 4496 nm with strong absorption in silica-based fibres is the longest emission wavelength from a CW fibre laser,and the span of 686 nm is also the largest tuning range achieved to date for any CW fibre laser.By further reducing the HCF transmission loss,increasing the pump power,improving the coupling efficiency,and optimizing the fibre length together with the pressure,the laser efficiency and output power are expected to increase significantly.This work opens new opportunities for broadly tunable high-power mid-IR fibre lasers,especially beyond 4μm.