Chiral Transfer and Evolution in Cysteine Induced Cobalt Superstructures.

Chiral organic additives have unveiled the extraordinary capacity to form chiral inorganic superstructures, however, complex hierarchical structures have hindered the understanding of chiral transfer and growth mechanisms. This study introduces a simple hydrothermal synthesis method for constructing chiral cobalt superstructures with cysteine, demonstrating specific recognition of chiral molecules and outstanding electrocatalytic activity. The mild preparation conditions allow in situ tracking of chirality evolution in the chiral cobalt superstructure, offering unprecedented insights into the chiral transfer and amplification mechanism. The resulting superstructures exhibit a universal formation process applicable to other metal oxides, extending the understanding of chiral superstructure evolution. This work contributes not only to the fundamental understanding of chirality in self-assembled structures but also provides a versatile method for designing chiral inorganic nanomaterials with remarkable molecular recognition and electrocatalytic capabilities.

Presynaptic density determined by SV2A PET is closely associated with postsynaptic metabotropic glutamate receptor 5 availability and independent of amyloid pathology in early cognitive impairment.

INTRODUCTION: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the pathophysiological mechanism of Alzheimer's disease (AD). METHODS: Ten cognitively impaired (CI) individuals and 10 healthy controls (HCs) underwent [18F]SynVesT-1 and [18F]PSS232 positron emission tomography (PET)/magnetic resonance to assess synaptic density and mGluR5 availability. The associations between mGluR5 availability and synaptic density were examined. A mediation analysis was performed to investigate the possible mediating effects of mGluR5 availability and synaptic loss on the relationship between amyloid deposition and cognition. RESULTS: CI patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and cognition. CONCLUSIONS: Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD and are closely linked. HIGHLIGHTS: Cognitively impaired patients exhibited lower mGluR5 availability and synaptic density in the medial temporal lobe than HCs. Reductions in mGluR5 availability and synaptic density exhibit similar spatial patterns in AD. Regional synaptic density was closely associated with regional mGluR5 availability. mGluR5 availability and synaptic loss partially mediated the relationship between amyloid deposition and global cognition. With further research, modulating mGluR5 availability might be a potential therapeutic strategy for improving synaptic function in AD.

Identification and Analysis of the MIR399 Gene Family in Grapevine Reveal Their Potential Functions in Abiotic Stress.

MiR399 plays an important role in plant growth and development. The objective of the present study was to elucidate the evolutionary characteristics of the MIR399 gene family in grapevine and investigate its role in stress response. To comprehensively investigate the functions of miR399 in grapevine, nine members of the Vvi-MIR399 family were identified based on the genome, using a miRBase database search, located on four chromosomes (Chr 2, Chr 10, Chr 15, and Chr 16). The lengths of the Vvi-miR399 precursor sequences ranged from 82 to 122 nt and they formed stable stem-loop structures, indicating that they could produce microRNAs (miRNAs). Furthermore, our results suggested that the 2 to 20 nt region of miR399 mature sequences were relatively conserved among family members. Phylogenetic analysis revealed that the Vvi-MIR399 members of dicots (Arabidopsis, tomato, and sweet orange) and monocots (rice and grapevine) could be divided into three clades, and most of the Vvi-MIR399s were closely related to sweet orange in dicots. Promoter analysis of Vvi-MIR399s showed that the majority of the predicted cis-elements were related to stress response. A total of 66.7% (6/9) of the Vvi-MIR399 promoters harbored drought, GA, and SA response elements, and 44.4% (4/9) of the Vvi-MIRR399 promoters also presented elements involved in ABA and MeJA response. The expression trend of Vvi-MIR399s was consistent in different tissues, with the lowest expression level in mature and young fruits and the highest expression level in stems and young leaves. However, nine Vvi-MIR399s and four target genes showed different expression patterns when exposed to low light, high light, heat, cold, drought, and salt stress. Interestingly, a putative target of Vvi-MIR399 targeted multiple genes; for example, seven Vvi-MIR399s simultaneously targeted VIT_213s0067g03280.1. Furthermore, overexpression of Vvi_MIR399e and Vvi_MIR399f in Arabidopsis enhanced tolerance to drought compared with wild-type (WT). In contrast, the survival rate of Vvi_MIR399d-overexpressed plants were zero after drought stress. In conclusion, Vvi-MIR399e and Vvi-MIR399f, which are related to drought tolerance in grapevine, provide candidate genes for future drought resistance breeding.

APOE ε4 is associated with decreased synaptic density in cognitively impaired participants.

INTRODUCTION: We aimed to investigate the effect of apolipoprotein E4 (APOE) ε4 on synaptic density in cognitively impaired (CI) participants. METHODS: One hundred ten CI participants underwent amyloid positron emission tomography (PET) with 18 F-florbetapir and synaptic density PET with 18 F-SynVesT-1. We evaluated the influence of APOE ε4 allele on synaptic density and investigated the effects of ε4 genotype on the associations of synaptic density with Alzheimer's disease (AD) biomarkers. The mediation effects of AD biomarkers on ε4-associated synaptic density loss were analyzed. RESULTS: Compared with non-carriers, APOE ε4 allele carriers exhibited significant synaptic loss in the medial temporal lobe. Amyloid beta (Aß) and tau pathology mediated the effects of APOE ε4 on synaptic density to different extents. The associations between synaptic density and tau pathology were regulated by the APOE ε4 genotype. DISCUSSION: The APOE ε4 allele was associated with decreased synaptic density in CI individuals and may be driven by AD biomarkers.

Chirality-enhanced 2D conductive polymer for flexible electronics and chiral sensing applications.

Chiral two-dimensional (2D) conductive polymers, encompassing chiral, 2D, flexible, and conductive properties, constitute a novel class of material that remains largely unexplored. The infusion of chirality into 2D conductive polymers taps into the unique characteristics associated with chirality, presenting opportunities to enhance or tailor the electronic, optical, and structural properties of materials for specific technological applications. In this study, we synthesized a chiral 2D PEDOT:PMo11V nanofilm through interfacial polymerization, effectively integrating a chiral monolayer, conductive polymer, and inorganic cluster. The inclusion of inorganic cluster serves to enhance the conductivity of the resulting chiral nanofilm. Furthermore, we demonstrated the chiral nanofilm as a capable electrochemical sensor for detecting drug enantiomers. The inherent flexibility of the chiral nanofilm also lays the groundwork for the development of chiral flexible/wearable devices.

Interfacial Interaction in NiFe LDH/NiS2/VS2 for Enhanced Electrocatalytic Water Splitting.

A bifunctional electrocatalyst with high efficiency and low costs for overall water splitting is critical to achieving a green hydrogen economy and coping with the energy crisis. However, developing robust electrocatalysts still faces huge challenges, owing to unsatisfactory electron transfer and inherent activity. Herein, NiFe LDH/NiS2/VS2 heterojunctions have been designed as freestanding bifunctional electrocatalysts to split water, exhibiting enhanced electron transfer and abundant catalytic sites. The optimum NiFe LDH/NiS2/VS2 electrocatalyst exhibits a small overpotential of 380 mV at 10 mA cm-2 for overall water splitting and superior electrocatalytic performance in both hydrogen and oxygen evolution reactions (HER/OER). Specifically, the electrocatalyst requires overpotentials of 76 and 286 mV at 10 mA cm-2 for HER and OER, respectively, in alkaline electrolytes, which originate from the synergistic interaction among the facilitated electron transfer and increasingly exposed active sites due to the modulation of interfaces and construction of heterojunctions.

Effect of lead-free glass on the current transmission method at the Ag/Si interface in crystalline silicon solar cells.

Environmental protection mandates have spurred the widespread adoption of lead-free glass in electronic material adhesion. Glass powder, crucial for solar silver paste, notably affects the ohmic contact at the Ag-Si interface of crystalline silicon solar cells. This study examines how TeO2 content influences the high-temperature flowability and wettability of lead-free Bi2O3-TeO2-based glass powder, alongside the interplay between the glass's thermal properties and interface contact. Additionally, it investigates the Bi2O3-TeO2 ratio's impact on current transmission through the interfacial glass layer. Experimental results show that the synthesized glass powder exhibits superior high-temperature flowability and wettability, with a low contact resistance of 1.5 mΩ cm2 in silver paste applications. This study also proposes an optimal approach for enhancing current transmission through the interfacial glass layer. Consequently, this glass powder is highly valuable for c-Si solar cell silver paste applications, offering novel insights into improving current transmission efficiency.

Metabotropic glutamate receptor 5 (mGluR5) is associated with neurodegeneration and amyloid deposition in Alzheimer's disease: A [18F]PSS232 PET/MRI study.

BACKGROUND: Metabotropic glutamate receptor 5 (mGluR5) is involved in regulating integrative brain function and synaptic transmission. Aberrant mGluR5 signaling and relevant synaptic failure play a key role in the initial pathophysiological mechanism of Alzheimer's disease (AD). The study aims to investigate the association between mGluR5 availability and AD's biomarkers and cognitive function. METHODS: We examined 35 individuals with mGluR5 tracer [18F]PSS232 to assess mGluR5 availability, and with [18F]Florbetapir PET to assess global amyloid deposition, and [18F]FDG PET to assess glucose metabolism. The plasma neurofilament light (NfL) and p-tau181 levels in a subset of individuals were measured (n = 27). The difference in mGluR5 availability between the AD and normal control (NC) groups was explored. The associations of mGluR5 availability with amyloid deposition, glucose metabolism, gray matter volume (GMV), neuropsychological assessment scores, and plasma biomarkers were analyzed. RESULTS: The mGluR5 availability was significantly reduced in AD patients' hippocampus and parahippocampal gyrus compared to NCs. Global amyloid deposition was positively associated with mGluR5 availability in the AD group and reversely associated in the NC group. The mGluR5 availability was positively correlated with regional glucose metabolism in the overall and stratified analyses. The availability of mGluR5 in the hippocampus and parahippocampal gyrus demonstrated a strong relationship with the GMV of the medial temporal lobe, plasma p-tau181 or NfL levels, and global cognitive performance. CONCLUSIONS: [18F]PSS232 PET can quantify the changes of mGluR5 availability in the progression of AD. mGluR5 availability correlated not only with neuropathological biomarkers of AD but also with neurodegenerative biomarkers and cognitive performance. mGluR5 may be a novel neurodegenerative biomarker, and whether mGluR5 could be a potential therapeutic target for AD needs to be further studied.

The associations between synaptic density and "A/T/N" biomarkers in Alzheimer's disease: An 18F-SynVesT-1 PET/MR study.

A newly developed SV2A radiotracer, 18F-SynVesT-1, was used in this study to investigate synaptic density and its association with Alzheimer's disease (AD) "A/T/N" biomarkers. The study included a cohort of 97 subjects, consisting of 64 patients with cognitive impairment (CI) and 33 individuals with normal cognition (CU). All subjects underwent 18F-SynVesT-1 PET/MR and 18F-florbetapir PET/CT scans. Additionally, a subgroup of individuals also underwent 18F-MK-6240, 18F-FDG PET/CT, plasma Aß42/Aß40 and p-tau181 tests. The differences in synaptic density between the groups and the correlations between synaptic density and AD "A/T/N" biomarkers were analyzed. The results showed that compared to the CU group, the CI with Aß+ (CI+) group exhibited the most pronounced synapse loss in the hippocampus, with some loss also observed in the neocortex. Furthermore, synaptic density in the hippocampus and parahippocampal gyrus showed associations with AD biomarkers detected by both imaging and plasma tests in the CI group. The associations between synaptic density and FDG uptake and hippocampal volume were also observed in the CI+ group. In conclusion, the study demonstrated significant synaptic density loss, as measured by the promising tracer 18F-SynVesT-1, and its close correlation with "A/T/N" biomarkers in patients with both Alzheimer's clinical syndrome and pathological changes.

Effect of Silver Powder Microstructure on the Performance of Silver Powder and Front-Side Solar Silver Paste.

Silver powder, as the primary component of solar silver paste, significantly influences various aspects of the paste's performance, including printing, sintering, and conductivity. This study reveals that, beyond the shape and size of the silver powders, their microstructure is a critical factor influencing the performance of both silver powders and silver pastes in solar cell applications. The growth process leads to the formation of either polycrystalline aggregated silver powder or crystal growth silver powder. Analyzing the performance characteristics of these different microstructures provides guidance for selecting silver powders for silver pastes at different sintering temperatures. Polycrystalline aggregated silver powder exhibits higher sintering activity, with a sintering initiation temperature around 450 °C. The resulting silver paste, sintered at 750 °C, demonstrates a low sheet resistance of 2.92 mΩ/sq and high adhesion of 2.13 N. This silver powder is suitable for formulating silver pastes with lower sintering temperatures. The solar cell electrode grid lines have a high aspect ratio of 0.37, showing poor uniformity. However, due to the high sintering activity of the silver powder, the glass layer dissolves and deposits more silver, resulting in excellent conductivity, a low contact resistance of the silver electrode, a low series resistance of the solar cell of 1.23 mΩ, and a high photoelectric conversion efficiency of 23.16%. Crystal growth silver powder exhibits the highest tap density of 5.52 g/cm3. The corresponding silver paste shows improved densification upon sintering, especially at 840 °C, yielding a sheet resistance of 2.56 mΩ/sq and adhesion of 3.05 N. This silver powder is suitable for formulating silver pastes with higher sintering temperatures. The solar cell electrode grid lines are uniform with the highest aspect ratio of 0.40, resulting in a smaller shading area, a high fill factor of 81.59%, and a slightly higher photoelectric conversion efficiency of 23.17% compared to the polycrystalline aggregated silver powder.

A rapid and highly efficient sorghum transformation strategy using GRF4-GIF1/ternary vector system.

Sorghum is an important crop for food, forage, wine and biofuel production. To enhance its transformation efficiency without negative developmental by-effects, we investigated the impact of GRF4-GIF1 chimaera and GRF5 on sorghum transformation. Both GRF4-GIF1 and GRF5 effectively improved the transformation efficiency of sorghum and accelerated the transformation process of sorghum to less than 2 months which was not observed when using BBM-WUS. As agrobacterium  effectors increase the ability of T-DNA transfer into plant cells, we checked whether ternary vector system can additively enhance sorghum transformation. The combination of GRF4-GIF1 with helper plasmid pVS1-VIR2 achieved the highest transformation efficiency, reaching 38.28%, which is 7.71-fold of the original method. Compared with BBM-WUS, overexpressing GRF4-GIF1 caused no noticeable growth defects in sorghum. We further developed a sorghum CRISPR/Cas9 gene-editing tool based on this GRF4-GIF1/ternary vector system, which achieved an average gene mutation efficiency of 41.36%, and null mutants were created in the T0 generation.

Clinical application of the modified neck-shoulder technique based on membrane autopsy to laparoscopic totally extraperitoneal prosthesis for indirect inguinal hernia.

OBJECTIVE: To investigate the anatomical basis and clinical application value of the modified neck-shoulder technique based on membrane autopsy in laparoscopic totally extraperitoneal prosthesis (TEP) for tension-free repairs of indirect inguinal hernia. METHODS: In this retrospective cohort study, we analyzed the clinical data of 136 patients with indirect inguinal hernia who underwent laparoscopic TEP for tension-free repairs at the Department of Gastroenterological Surgery Unit 1, the First Hospital of Putian City, Fujian Province from June 2017 to June 2020. The patients were divided into the modified neck-shoulder technique group (68 cases) and the traditional surgery group (68 cases), according to the different surgical methods. The intraoperative and postoperative conditions of the two groups were compared. RESULTS: Both the modified neck-shoulder technique group and the traditional surgery group completed the herniorrhaphy. Compared with the traditional surgery group, the modified neck-shoulder technique group had a shorter operation time [(37.15 ± 5.320) min vs. (54.04 ± 5.202) min, t = 18.472, p < 0.001], less intraoperative blood loss [(5.53 ± 1.634) ml vs. (16.21 ± 3.375) ml, t = 23.544, p < 0.001], lower incidence of intraoperative peritoneal injury [3 cases (4.41%) vs. 9 cases (13.26%), χ2 = 3.29, p = 0.07], lower intraoperative conversion rate [1 case (1.47%) vs. 8 cases (11.76%), χ2 = 5.83, p = 0.016], and lower incidence of postoperative chronic pain [1 case (1.47%) vs. 12 cases (17.65%), χ2 = 10.291, p = 0.001], all of which were statistically significant (p < 0.05). Both groups were followed up for 12 months after surgery. Relapse was not observed in any case. CONCLUSION: Drawing upon the surgical principles of the open neck-shoulder technique and the understanding of the membrane autopsy in the inguinal region, our center has summarized a set of operation procedures called the "modified neck-shoulder technique" for laparoscopic TEP in the tension-free repairs of indirect inguinal hernias. This new surgical technique could expeditiously and precisely navigate the interlayer gap in the preperitoneal space under the enlarged view of the laparoscope. It facilitated the high ligation, disconnection, or repositioning of the hernia sac, enhancing the reliability of patch placement while minimizing collateral damage, reducing postoperative complications, and shortening operation time.

Fixed-Time Composite Neural Learning Control of Flexible Telerobotic Systems.

This article is devoted to the fixed-time synchronous control for a class of uncertain flexible telerobotic systems. The presence of unknown joint flexible coupling, time-varying system uncertainties, and external disturbances makes the system different from those in the related works. First, the lumped system dynamics uncertainties and external disturbances are estimated successfully by designing a new composite adaptive neural networks (CANNs) learning law skillfully. Moreover, the fast-transient, satisfactory robustness, and high-precision position/force synchronization are also realized by design of fixed-time impedance control strategies. Furthermore, the "complexity explosion" issue triggered by traditional backstepping technology is averted efficiently via a novel fixed-time command filter and filter compensation signals. And then, sufficient conditions of system controller parameters and fixed-time stability are theoretically given by establishing the Lyapunov stability theorem. Besides, the absolute stability of the two-port networked system under complex transmission time delays is rigorously proved. Finally, simulations are performed with 2-link flexible telerobotic systems under two cases, results are presented to realistically verify the proposed control algorithm available.

Comprehensive analysis of necroptotic patterns and associated immune landscapes in individualized treatment of skin cutaneous melanoma.

Skin cutaneous melanoma (SKCM) constitutes a malignant cutaneous neoplasm characterized by an exceedingly unfavorable prognosis. Over the past years, necroptosis, a manifestation of inflammatory programmed cell demise, has gained substantial traction in its application. However, a conclusive correlation between the expression of necroptosis-related genes (NRGs) and SKCM patient's prognosis remains elusive. In this endeavor, we have undertaken an integrative analysis of genomic data, aiming to provide an exhaustive evaluation of the intricate interplay between melanoma necroptosis and immune-infiltration nuances within the tumor microenvironment. Through meticulous scrutiny, we have endeavored to discern the prognostic potency harbored by individual necroptosis-associated genes. Our efforts culminated in the establishment of a risk stratification framework, allowing for the appraisal of necroptosis irregularities within each afflicted cutaneous melanoma patient. Notably, those SKCM patients classified within the low-risk cohort exhibited a markedly elevated survival quotient, in stark contrast to their high-risk counterparts (p < 0.001). Remarkably, the low-risk cohort not only displayed a more favorable survival rate but also exhibited an enhanced responsiveness to immunotherapeutic interventions, relative to their high-risk counterparts. The outcomes of this investigation proffer insights into a conceivable mechanistic underpinning linking necroptosis-related attributes to the intricacies of the tumor microenvironment. This prompts a conjecture regarding the plausible association between necroptosis characteristics and the broader tumor microenvironmental milieu. However, it is imperative to emphasize that the pursuit of discerning whether the expression profiles of NRG genes can indeed be regarded as viable therapeutic targets necessitates further comprehensive exploration and scrutiny. In conclusion, our study sheds light on the intricate interrelationship between necroptosis-related factors and the tumor microenvironment, potentially opening avenues for therapeutic interventions. However, the prospect of translating these findings into clinical applications mandates rigorous investigation.

Positive rate and quantification of amyloid pathology with [18F]florbetapir in the urban Chinese population.

OBJECTIVES: Amyloid deposition is considered the initial pathology in Alzheimer's disease (AD). Personalized management requires investigation of amyloid pathology and the risk factors for both amyloid pathology and cognitive decline in the Chinese population. We aimed to investigate amyloid positivity and deposition in AD patients, as well as factors related to amyloid pathology in Chinese cities. METHODS: This cross-sectional multicenter study was conducted in Shanghai and Zhengzhou, China. All participants were recruited from urban communities and memory clinics. Amyloid positivity and deposition were analyzed based on amyloid positron emission tomography (PET). We used partial least squares (PLS) models to investigate how related factors contributed to amyloid deposition and cognitive decline. RESULTS: In total, 1026 participants were included: 768 participants from the community-based cohort (COMC) and 258 participants from the clinic-based cohort (CLIC). The overall amyloid-positive rates in individuals with clinically diagnosed AD, mild cognitive impairment (MCI), and normal cognition (NC) were 85.8%, 44.5%, and 26.9%, respectively. The global amyloid deposition standardized uptake value ratios (SUVr) (reference: cerebellar crus) were 1.44 ± 0.24, 1.30 ± 0.22, and 1.24 ± 0.14, respectively. CLIC status, apolipoprotein E (ApoE) ε4, and older age were strongly associated with amyloid pathology by PLS modeling. CONCLUSION: The overall amyloid-positive rates accompanying AD, MCI, and NC in the Chinese population were similar to those in published cohorts of other populations. ApoE ε4 and CLIC status were risk factors for amyloid pathology across the AD continuum. Education was a risk factor for amyloid pathology in MCI. Female sex and age were risk factors for amyloid pathology in NC. CLINICAL RELEVANCE STATEMENT: This study provides new details about amyloid pathology in the Chinese population. Factors related to amyloid deposition and cognitive decline can help to assess patients' AD risk. KEY POINTS: • We studied amyloid pathology and related risk factors in the Chinese population. •·The overall amyloid-positive rates in individuals with clinically diagnosed AD, MCI, and NC were 85.8%, 44.5%, and 26.9%, respectively. • These overall amyloid-positive rates were in close agreement with the corresponding prevalence for other populations.

Pure Amorphous and Ultrathin Phosphate Layer with Superior Ionic Conduction for Zinc Anode Protection.

Fast and uniform ion transport within the solid electrolyte interphase (SEI) is considered a crucial factor for ensuring the long-term stability of metal electrodes. In this study, we present the fabrication of ultrathin artificial interphases consisting of a zinc phosphate nanofilm with pure amorphous characteristics and a surfactant overlayer. The thickness of the interphases can be precisely controlled within the range of a few tens of nanometers. We explore the impact of artificial SEI structure, including thickness and crystallinity, on its protective capabilities. The pure amorphous phosphate layer with optimized nanoscale thickness is found to provide an abundance of short and isotropic ion migration pathways and a low diffusion energy barrier. These features facilitate rapid and homogeneous Zn2+ transportation, resulting in compact and planar zinc deposition. Meanwhile, the hydrophobic alkyl moieties of the overlayer prevent disassociation of water at the interface. As a result, this nanofilm endures ultralong cycling stability with a low overpotential and enables high Zn plating/stripping reversibility. The Zn||MnO2 full cell shows a stable cycle life for 700 cycles under practical conditions of lean electrolyte, high areal capacity cathode, and limited Zn excess. These findings provide insights into the design and optimization of SEI layers for protection of metal anodes.

Study on Low-Temperature Conductive Silver Pastes Containing Bi-Based Glass for MgTiO3 Electronic Power Devices.

Low-temperature lead-free silver pastes deserve thorough investigation for sustainable development and application of MgTiO3 ceramics in electronic devices. In this study, a series of Bi2O3-B2O3-ZnO-SiO2-Al2O3-CaO glasses with suitable softening temperatures were prepared via melt quenching using a type of micrometer silver powder formed by silver nanoparticle aggregates. The composite pastes containing silver powder, Bi2O3 glass powder and an organic vehicle were then screen-printed. The effects of glass powder concentration and sintering temperature on the microstructure of the surface interface were also investigated. The results showed that the silver paste for microwave dielectric ceramic filters (MgTiO3) possessed good electrical conductivity (2.28 mΩ/□) and high adhesion (43.46 N/mm2) after medium temperature (670 °C) sintering. Thus, this glass powder has great application potential in non-toxic lead-free silver pastes for metallization of MgTiO3 substrates.

Solvatochromic sensors detect proteome aggregation in stressed liver tissues with hepatic cancer and cirrhosis.

Protein misfolding and aggregation involve complex cellular processes with clinical implications in various diseases. However, the detection of aggregated proteomes without defined 3-D structures in a complex biological milieu is challenging. This study utilizes chromone scaffold-based environment-sensitive fluorophores P1 and P2 to detect misfolded and aggregated proteome in stressed liver cells and the liver tissues diseased patients. The reported crystallization induced emission probes (P1 and P2) exhibit both polarity and viscosity sensitivity, with emission intensity and wavelength linearly correlated to viscosity and polarity. Meanwhile, P1 and P2 selectively and generally fluoresce upon binding to various aggregated proteins. In hepatic cells, P2 outperforms P1 in detecting stress-induced global proteome aggregation. In mouse liver tissue upon drug-induced injury, the fluorescence intensity of P2 correlated with the severity of liver injury, serving as an earlier indicator for liver stress prior to ALT/AST increase. The quantification of emission wavelength reveals lower micro-environmental polarity in liver-injury tissue. In patient-derived tissues with hepatic cancer and cirrhosis, P1 and P2 also report on the presence of aggregated proteome. Together, the reported solvatochromic proteome aggregation sensors can detect hepatic proteome aggregation and analyze its local polarity in cultured cell lines, animal model tissues, and human clinical samples.

Evaluation of HPV infection helps to direct ALA-PDT of condyloma acuminata.

BACKGROUND AND OBJECTIVES: Aminolaevulinic acid-mediated photodynamic therapy (ALA-PDT) is increasingly applied for the treatment of condyloma acuminata (CA). However, the determinants for the sessions and end points of ALA-PDT treatment remains unclear. Here, we recorded HPV screening, evaluated the frequency and efficacy of ALA-PDT in different types of CA, in order to individualize ALA-PDT treatment to CA. METHODS: A total of 227 CA patients with HPV infection and visible warts were recruited. Prior to PDT, visible lesions were removed by radio frequency or microwave. HPV DNA detection were performed before each PDT treatment and at follow-up. Treatment was ended after two consecutive negative HPV DNA detection. RESULTS: Of the 227 patients, 119 patients received ALA-PDT and 116 patients completed all treatments. We found that CA patients with multiple-site infection, intra-luminal infection or multiple-type of HPV infection required more sessions of ALA-PDT. The recurrence rate was 8.62% (10/116). Viral load was significantly lower after six PDT treatments compared to viral load after three PDT treatments. Gender, HPV subtypes and warts location had no significant effect on the recurrence rate. CONCLUSION: Comprehensive evaluation of HPV infection state helps to individualize ALA-PDT treatment scheme for CA patients and predict the therapeutic efficacy.

Functional Differences of Grapevine Circular RNA Vv-circPTCD1 in Arabidopsis and Grapevine Callus under Abiotic Stress.

Circular RNAs (circRNAs) serve as covalently closed single-stranded RNAs and have been proposed to influence plant development and stress resistance. Grapevine is one of the most economically valuable fruit crops cultivated worldwide and is threatened by various abiotic stresses. Herein, we reported that a circRNA (Vv-circPTCD1) processed from the second exon of the pentatricopeptide repeat family gene PTCD1 was preferentially expressed in leaves and responded to salt and drought but not heat stress in grapevine. Additionally, the second exon sequence of PTCD1 was highly conserved, but the biogenesis of Vv-circPTCD1 is species-dependent in plants. It was further found that the overexpressed Vv-circPTCD1 can slightly decrease the abundance of the cognate host gene, and the neighboring genes are barely affected in the grapevine callus. Furthermore, we also successfully overexpressed the Vv-circPTCD1 and found that the Vv-circPTCD1 deteriorated the growth during heat, salt, and drought stresses in Arabidopsis. However, the biological effects on grapevine callus were not always consistent with those of Arabidopsis. Interestingly, we found that the transgenic plants of linear counterpart sequence also conferred the same phenotypes as those of circRNA during the three stress conditions, no matter what species it is. Those results imply that although the sequences are conserved, the biogenesis and functions of Vv-circPTCD1 are species-dependent. Our results indicate that the plant circRNA function investigation should be conducted in homologous species, which supports a valuable reference for further plant circRNA studies.