A nanoenzyme-modified hydrogel targets macrophage reprogramming-angiogenesis crosstalk to boost diabetic wound repair.

Diabetic wounds has a gradually increasing incidence and morbidity. Excessive inflammation due to immune imbalance leads to delayed wound healing. Here, we reveal the interconnection between activation of the NLRP3 inflammatory pathway in endotheliocyte and polarization of macrophages via the cGAS-STING pathway in the oxidative microenvironment. To enhance the immune-regulation based on repairing mitochondrial oxidative damage, a zeolitic imidazolate framework-8 coated with cerium dioxide that carries Rhoassociated protein kinase inhibition Y-27632 (CeO2-Y@ZIF-8) is developed. It is encapsulated in a photocross-linkable hydrogel (GelMA) with cationic quaternary ammonium salt groups modified to endow the antibacterial properties (CeO2-Y@ZIF-8@Gel). CeO2 with superoxide dismutase and catalase activities can remove excess reactive oxygen species to limit mitochondrial damage and Y-27632 can repair damaged mitochondrial DNA, thus improving the proliferation of endotheliocyte. After endotheliocyte uptakes CeO2-Y@ZIF-8 NPs to degrade peroxides into water and oxygen in cells and mitochondria, NLRP3 inflammatory pathway is inhibited and the leakage of oxidatively damaged mitochondrial DNA (Ox-mtDNA, a damage-associated molecular pattern) through mPTP decreases. Futhermore, as the cGAS-STING pathway activated by Ox-mtDNA down-regulated, the M2 phenotype polarization and anti-inflammatory factors increase. Collectively, CeO2-Y@ZIF-8@Gel, through remodulating the crosstalk between macrophage reprogramming and angiogenesis to alleviate inflammation in the microenvironment and accelerates wound healing.

Critical quality appraisal and algorithm development of clinical practice guidelines for management of poststroke sensory loss: a systematic review.

OBJECTIVES: This study aimed to assess the methodological quality of clinical practice guidelines (CPGs) associated with the management of poststroke sensory loss and develop an algorithm for health professionals. METHODS: We conducted a systematic review for relevant CPGs published between 2017 and 2022 using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Checklist. Appraisal of Guidelines for Research and Evaluation II instrument was used to assess methodological quality. Recommendations for managing poststroke sensory loss from high and average-quality CPGs were summarised and developed into an algorithm. RESULTS: First, 1458 records were identified from the database searches and other sources. Finally, four CPGs were included: three were rated as high quality and one as average quality. Twenty-two recommendations were summarised from these CPGs and used to develop a draft algorithm. Then, we revised the draft algorithm developed by the authors based on expert feedback to form the final version. CONCLUSIONS: The four CPGs included in this study had good quality. Based on these CPGs, we developed an algorithm to facilitate health professionals' adherence to CPGs and contribute to evidence-based medicine. In the future, more high-quality CPGs are required to give further scientific and convincing evidence to manage poststroke sensory loss.

A Sustained-Release Nanosystem with MRSA Biofilm-Dispersing and -Eradicating Abilities Accelerates Diabetic Ulcer Healing.

Introduction: Drug-resistant bacterial infections and biofilm formation play important roles in the pathogenesis of diabetic refractory wounds. Tea tree oil (TTO) exhibits antimicrobial, antimycotic, and antiviral activities, especially against common clinically resistant strains, such as methicillin-resistant Staphylococcus aureus (MRSA), making it a potential natural antimicrobial for the treatment of acute and chronic wounds. However, TTO is insoluble in water, volatile, light-sensitive, and cytotoxic. While previous macroscopic studies have focused on sterilization with TTO, none have sought to alter its structure or combine it with other materials to achieve sustained release. Methods: Electrospun TTO nanoliposomes (TTO-NLs), arranged linearly via high-pressure homogenization, could stabilize the structure and performance of TTO to achieve slow drug release. Herein, we established a composite nano-sustained release system, TTO-NL/polyvinyl alcohol/chitosan (TTO-NL@PCS), using high-voltage electrospinning. Results: Compared with the control, TTO-NL@PCS exhibits higher concentrations of the active TTO drug components, terpinen-4-ol and 1,8-cineole. Owing to its increased stability and slow release, early exposure to TTO-NL@PCS increases the abundance of reactive oxygen species in vitro, ultimately causing the biofilm to disperse and completely killing MRSA without inducing cytotoxic effects to the host. Moreover, in BKS-Leprem2Cd479/Gpt mice with a whole-layer skin infection, untargeted metabolomics analysis of wound exudates reveals upregulated PGF2α/FP receptor signaling and interleukin (IL)-1ß and IL-6 expression following application of the composite system. The composite also ameliorates the chemotaxis disorder in early treatment and attenuates the wound inflammatory response during the repair stage of diabetic inflammatory wounds, and upregulates VEGF expression in the wound bed. Conclusion: TTO-NL@PCS demonstrates the remarkable potential for accelerating diabetic and MRSA-infected wound healing.

Skin infectome of patients with a tick bite history.

Introduction: Ticks are the most important obligate blood-feeding vectors of human pathogens. With the advance of high-throughput sequencing, more and more bacterial community and virome in tick has been reported, which seems to pose a great threat to people. Methods: A total of 14 skin specimens collected from tick-bite patients with mild to severe symptoms were analyzed through meta-transcriptomic sequencings. Results: Four bacteria genera were both detected in the skins and ticks, including Pseudomonas, Acinetobacter, Corynebacterium and Propionibacterium, and three tick-associated viruses, Jingmen tick virus (JMTV), Bole tick virus 4 (BLTV4) and Deer tick mononegavirales-like virus (DTMV) were identified in the skin samples. Except of known pathogens such as pathogenic rickettsia, Coxiella burnetii and JMTV, we suggest Roseomonas cervicalis and BLTV4 as potential new agents amplified in the skins and then disseminated into the blood. As early as 1 day after a tick-bite, these pathogens can transmit to skins and at most four ones can co-infect in skins. Discussion: Advances in sequencing technologies have revealed that the diversity of tick microbiome and virome goes far beyond our previous understanding. This report not only identifies three new potential pathogens in humans but also shows that the skin barrier is vital in preventing horizontal transmissions of tick-associated bacteria or virus communities to the host. It is the first research on patients' skin infectome after a tick bite and demonstrates that more attention should be paid to the cutaneous response to prevent tick-borne illness.

Analysis of influencing factors on monohydroxylated derivative of oxcarbazepine plasma concentration in children with epilepsy.

PURPOSE: This study aimed to investigate the factors affecting the plasma concentration of monohydroxylated derivative (MHD) of oxcarbazepine (OXC) in children with epilepsy. METHODS: We recruited 125 children with epilepsy who received OXC monotherapy. Among them, 16 single nucleotide polymorphisms were detected by MassARRAY genotyping technology to evaluate the influence of related factors on the plasma concentration of OXC monotherapy. MHD is the main active metabolite of OXC, and its plasma concentration was measured by high-performance liquid chromatography (HPLC). RESULTS: Bivariate correlation analysis revealed that concentration-dose ratio (CDR) increased with weight, and the corresponding maintenance dose decreased with weight (r=0.317, P=0.001 for CDR; r=-0.285, P=0.000 for OXC maintenance dose). The duration of seizure was found to be associated with CDR (0.90 ± 0.36 vs 0.74 ± 0.26 µg·kg/mg/mL for ≥6 years vs <1 year, P=0.028; 0.90 ± 0.36 vs 0.64 ± 0.21 µg·kg/mg/mL for ≥6 years vs 1-3 years, P=0.004; 0.90 ± 0.36 vs 0.69 ± 0.18 µg·kg/mg/mL for ≥6 years vs 3-6 years, P=0.031). The CDR of patients with ABCB1 rs1045642 mutation homozygous GG type is higher than heterozygous AG type (0.79 ± 0.30 vs 0.68 ± 0.20 µg·kg/mg/mL for AG vs GG, P=0.032). CONCLUSION: This study clarified the association of weight, duration of seizure, and gene polymorphisms of ABCB1 rs1045642 with MHD plasma concentration in children with epilepsy.

A Novel Enzyme-Free Ratiometric Fluorescence Immunoassay Based on Silver Nanoparticles for the Detection of Dibutyl Phthalate from Environmental Waters.

A novel ratiometric fluorescent immunoassay was developed based on silver nanoparticles (AgNPs) for the sensitive determination of dibutyl phthalate (DBP). In the detection system, AgNPs were labeled on the secondary antibody (AgNPs@Ab2) for signal amplification, which aimed to regulate the H2O2 concentrations. When AgNPs-Ab2 and antigen-primary antibody (Ab1) were linked by specific recognition, the blue fluorescence of Scopoletin (SC) could be effectively quenched by the H2O2 added while the red fluorescence of Amplex Red (AR) was generated. Under the optimized conditions, the calculated detection of limit (LOD, 90% inhibition) reached 0.86 ng/mL with a wide linear range of 2.31-66.84 ng/mL, which was approximately eleven times lower than that by HRP-based traditional ELISA with the same antibody. Meanwhile, it could improve the inherent built-in rectification to the environment by the combination of the dual-output ratiometric fluorescence assays with ELISA, which also enhanced the accuracy and precision (recoveries, 87.20-106.62%; CV, 2.57-6.54%), indicating it can be applied to investigate the concentration of DBP in water samples.

Management of cardiovascular disease in women with premature ovarian insufficiency: critical quality appraisal of clinical guidelines and algorithm development.

OBJECTIVES: 1) To assess the methodological quality of clinical practice guidelines (CPGs) associated with cardiovascular disease (CVD) in women with premature ovarian insufficiency (POI); 2) to formulate an algorithm to foster the implementation of guidelines by clinicians. METHODS: A systematic search for CPGs in English and Chinese languages published between 2015 and 2020 was conducted. Assessment was conducted by two reviewers respectively via the Appraisal of Guidelines for Research and Evaluation II instrument. The interappraisal agreement was evaluated. Recommendations pertaining to the management of CVD in women with POI were extracted from high-score CPGs and developed into an algorithm, which was refined on the basis of expert feedback. RESULTS: A total of 14 CPGs were included. Three CPGs were evaluated as "high quality," with five "average" and six considered "low quality." The consistency of agreement between reviewers was considered as substantial agreement to almost perfect agreement (0.72-0.90). The algorithm consisted of three categories: initial evaluation, management, and subsequent monitoring of CVD in POI. Only "management" had recommendations from all three high-quality CPGs. CONCLUSIONS: The overall methodological quality of most CPGs regarding CVD in women with POI is moderate to poor. A management algorithm with a clear implementation strategy was developed from high-scoring CPGs. Further research is needed to provide evidence-based health care in this field.

Immunoproteasome modulates NLRP3 inflammasome-mediated neuroinflammation under cerebral ischaemia and reperfusion conditions.

Compelling evidence showed that both nucleotide-binding oligomerization domain-like receptor family, pyrin domain-containing protein 3 (NLRP3) inflammasomes and the immunoproteasome participate in neuroinflammatory responses in cerebral ischaemia injury. Moreover, inhibition of either NLRP3 inflammasomes or the immunoproteasome attenuates both neuroinflammation and neurological deterioration during ischaemic stroke. However, the underlying mechanism between the immunoproteasome and NLRP3 inflammasomes under ischaemic stroke conditions remains to be established. In this study, using both in vitro and in vivo ischaemic models, we demonstrated that the immunoproteasome inhibition reduced the expressions of NLRP3 inflammasome-associated proteins, including NLRP3, apoptosis-associated speck-like protein (ASC), caspase-1 and mature cytokines (interleukin [IL]-1ß and IL-18). It also downregulated the levels of nuclear factor (NF)-κB and pyroptotic- and apoptotic-related proteins, and improved cell viability. In addition, inhibition of NF-κB by the small molecule inhibitor Bay-11-7082 led to lower levels of NLRP3 inflammasomes and cleaved caspase-1 proteins in BV2 cells after oxygen-glucose deprivation and reoxygenation. Together, these findings suggest that the immunoproteasome may be responsible for inducing the expression and activation of NLRP3 inflammasomes via the NF-κB pathway. Therapeutic interventions that target activation of the immunoproteasome/NF-κB/NLRP3 inflammasome pathway may provide novel prospects for the future treatment of ischaemic stroke.

Inhibition of the immunoproteasome LMP2 ameliorates ischemia/hypoxia-induced blood-brain barrier injury through the Wnt/ß-catenin signalling pathway.

BACKGROUND: Disruption of the blood-brain barrier (BBB) after a stroke can lead to brain injury and neurological impairment. Previous work confirmed the involvement of the immunoproteasome subunit of low molecular mass peptide 2 (LMP2) in the pathophysiology of ischemia stroke. However, the relationship between the immunoproteasome LMP2 and the BBB remains unclear. METHODS: Adult male Sprague-Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion (MCAO/R). Three days before MCAO, the rats were treated with lentivirus-mediated LMP2 shRNA preparations by stereotactical injection into the ipsilateral hemispheric region. The rat brain microvascular endothelial cell (RBMVEC) line was exposed to oxygen-glucose deprivation/reperfusion (OGD/R) to mimic ischemic conditions in vitro. The RNA interference-mediated knockdown of LMP2 or ß-catenin was analysed in vivo and in vitro. Analysis of the quantity of extravasated Evans blue (EB) and cerebral fluorescent angiography were performed to evaluate the integrity of the BBB. Immunofluorescence and Western blotting were employed to detect the expression of target proteins. Cell migration was evaluated using a scratch migration assay. The results of immunofluorescence, Western blotting and cell migration were quantified using the software ImageJ (Version 1.53m). Parametric data from different groups were compared using one-way ANOVA followed by the least significant difference (LSD) test. RESULTS: Cerebral ischemia led to lower levels of structural components of the BBB such as tight junction proteins (occludin, claudin-1 and ZO-1) in the MCAO/R group compared with the sham group (P < 0.001). However, inhibition of the immunoproteasome LMP2 restored the expression of these proteins, resulting in higher levels of occludin, claudin-1 and ZO-1 in the LMP2-shRNA group compared with the control-shRNA group (P < 0.001). In addition, inhibition of the immunoproteasome LMP2 contributed to higher microvascular density and decreased BBB permeability [e.g., the quantity of extravasated EB: LMP2-shRNA group (58.54 ± 7.37) µg/g vs. control-shRNA group (103.74 ± 4.32) µg/g, P < 0.001], and promoted the upregulation of Wnt-3a and ß-catenin proteins in rats following MCAO/R. In vitro experiments, OGD/R induced marked upregulation of LMP2, proapoptotic protein Bax and cleaved caspase-3, and downregulation of occludin, claudin-1, ZO-1 and Bcl-2, as well as inhibition of the Wnt/ß-catenin pathway Wnt-3a and ß-catenin proteins in RBMVECs, compared with the control group under normal culture conditions (P < 0.001). However, silencing of LMP2 gene expression reversed these protein changes and promoted proliferation and migration of RBMVECs following OGD/R. Silencing of ß-catenin by transfection of RBMVECs with ß-catenin-siRNA aggravated the downregulation of tight junction proteins, and reduced the proliferation and migration of RBMVECs following OGD/R, compared with the control-siRNA group (P < 0.001). LMP2-siRNA and ß-catenin-siRNA co-transfection partly counteracted the beneficial effects of silencing LMP2-siRNA on the levels of tight junction proteins in RBMVECs exposed to OGD/R. CONCLUSION: This study suggests that inhibition of the immunoproteasome LMP2 ameliorates ischemia/hypoxia-induced BBB injury, and that the molecular mechanism involves the immunoproteasome-regulated activation of the Wnt/ß-catenin signalling pathway under ischemic conditions.

Inhibition of the Immunoproteasome Subunit LMP7 Ameliorates Cerebral White Matter Demyelination Possibly via TGFß/Smad Signaling.

OBJECTIVES: Chronic cerebral hypoperfusion induces white matter ischemic injury and cognitive impairment, whereas the mechanism remains unclear. Immunoproteasomes have been implicated in the pathogenesis of acute ischemia stroke and multiple sclerosis. However, the expression and role of immunoproteasomes in the brain of chronic cerebral hypoperfusion remain to be clarified. METHODS: Chronic white matter ischemic injury mice models were induced by bilateral carotid artery stenosis (BCAS). A selective immunoproteasome subunit low-molecular-mass peptide-7 (LMP7) inhibitor PR957 was administered to mice. Cognitive function, white matter integrity, and potential pathways were assessed after BCAS. RESULTS: The present study found that chronic cerebral hypoperfusion following BCAS induced cerebral white matter demyelination and cognitive impairment, accompanied with elevated expression of the immunoproteasomes LMP2 and LMP7, activation of astrocytes and microglia, and increased production of inflammatory cytokines (e.g., interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), IL-10, transforming growth factor-ß1 (TGFß1), and insulin-like growth factor-1 (IGF-1)). However, inhibition of LMP7 with the specific proteasome inhibitor PR957 significantly mitigated the histological damage of the white matter, suppressed inflammatory response, and paralleled by an improvement of cognitive function. Furthermore, treatment of PR957 significantly upregulated the level of TGFß1, the total expression level, and the phosphorylation level of Smad2/3 and promoted brain remyelination. Surprisingly, PR957 alone had no effects on the neuroinflammation response and the activation of TGFß/Smad signaling in the sham-operated (BCAS-nonoperated) mice. CONCLUSIONS: The possible mechanism underlying this was attributed to that the immunoproteasome regulates TGFß/Smad signaling-mediated neuroinflammation and oligodendrocyte remyelination.

Unveiling structure-performance relationships from multi-scales in non-fullerene organic photovoltaics.

Unveiling the correlations among molecular structures, morphological characteristics, macroscopic properties and device performances is crucial for developing better photovoltaic materials and achieving higher efficiencies. To achieve this goal, a comprehensive study is performed based on four state-of-the-art non-fullerene acceptors (NFAs), which allows to systematically examine the above-mentioned correlations from different scales. It's found that extending conjugation of NFA shows positive effects on charge separation promotion and non-radiative loss reduction, while asymmetric terminals can maximize benefits from both terminals. Another molecular optimization is from alkyl chain tuning. The shortened alkyl side chain results in strengthened terminal packing and decreased π-π distance, which contribute high carrier mobility and finally the high charge collection efficiency. With the most-acquired benefits from molecular structure and macroscopic factors, PM6:BTP-S9-based organic photovoltaics (OPVs) exhibit the optimal efficiency of 17.56% (certified: 17.4%) with a high fill factor of 78.44%, representing the best among asymmetric acceptor based OPVs. This work provides insight into the structure-performance relationships, and paves the way toward high-performance OPVs via molecular design.

Efficient Charge Transport Enables High Efficiency in Dilute Donor Organic Solar Cells.

The donor/acceptor weight ratio is crucial for photovoltaic performance of organic solar cells (OSCs). Here, we systematically investigate the photovoltaic behaviors of PM6:Y6 solar cells with different stoichiometries. It is found that the photovoltaic performance is tolerant to PM6 contents ranging from 10 to 60 wt %. Especially an impressive efficiency over 10% has been achieved in dilute donor solar cells with 10 wt % PM6 enabled by efficient charge generation, electron/hole transport, slow charge recombination, and field-insensitive extraction. This raises the question about the origin of efficient hole transport in such dilute donor structure. By investigating hole mobilities of PM6 diluted in Y6 and insulators, we find that effective hole transport pathway is mainly through PM6 phase in PM6:Y6 blends despite with low PM6 content. The results indicate that a low fraction of polymer donors combines with near-infrared nonfullerene acceptors could achieve high photovoltaic performance, which might be a candidate for semitransparent windows.

Fast Field-Insensitive Charge Extraction Enables High Fill Factors in Polymer Solar Cells.

Fill factor (FF) is a determining parameter for the power conversion efficiency (PCE) of organic solar cells (OSC). So far, nonfullerene (NF) OSCs with state-of-the-art PCEs exhibit FFs <0.8, lower than the values of Si or perovskite solar cells. The FFs directly display the dependence of photocurrent on bias, meaning that the competition between charge extraction and recombination is modulated by internal electric potential (Vin). Here, we report a study to understand key parameters/properties affecting the device FF based on seven groups of NF-OSCs consisting of widely used PBDBT-2F or PTB7-Th donors and representative NF-acceptors with FFs ranging from 0.60 to 0.78 and PCEs from 10.27 to 16.09%. We used field-dependent transient photocurrent measurements to reveal that fast and field-insensitive charge extraction at low Vin is an essential prerequisite for obtaining high FFs (0.75-0.8), which is enabled by balanced charge transport in steady and reduced bimolecular charge recombination in high purity phases. With bias-dependent quantum efficiency analysis, we further show that the recombination loss at low Vin in the devices with low FFs tends to be more significant involving excitons generated in the donor phase of blends. Our results provide relevance for how to improve the FF toward the boost of photovoltaic performance in NF-OSCs.

Complex spatial patterns delay the discovery and location of food by rodents.

Spatial patterns in heterogeneity are generally deemed a central causal factor influencing the physiology and behavior of animals in ecological systems. However, knowledge remains limited about how such patterns influence food discovery by animals. We inferred that spatial heterogeneity plays a key role in animal food discovery and location. To prove this inference, we tested food locating parameters by 2 rodent species, Apodemus agrarius and Lasiopodomys brandtii, in different heterogeneous environments. Our results showed that spatial heterogeneity significantly influenced the food locating time of rodents, with food locating time increasing with increasing spatial heterogeneity. Furthermore, spatial heterogeneity significantly influenced invalid excavations (digging in the wrong place). Finally, spatial heterogeneity significantly influenced the frequency that heterogeneous objects were explored. Supporting our inference, our results indicate that spatial heterogeneity significantly influences the foraging behavior of animals. Consequently, increased spatial heterogeneity will impair the food locating success of rodents. We believe that this work will broaden our understanding of plant-animal interactions.

A Comparative Study on Hole Transfer Inversely Correlated with Driving Force in Two Non-Fullerene Organic Solar Cells.

We report a faster rate of hole transfer under a smaller ΔHOMO in a comparative study of two group organic solar cells (OSCs) consisting of IT-4F as an acceptor and PBDBT and PBDBT-SF as donors. In the OSCs based on PBDBT-SF:IT-4F, a higher short-circuit current (JSC) was observed with a ΔHOMO of 0.31 eV compared to a lower JSC in PBDBT:IT-4F OSCs with a larger ΔHOMO (0.45 eV). Intensive investigation indicates that the rate of transfer of a hole from IT-4F to PBDBT-SF or PBDBT is inversely proportional to the ΔHOMO between IT-4F and donors. The larger JSC in the PBDBT-SF:IT-4F device is attributed to a synergy of faster hole transfer, slower recombination, and rapid charge extraction enabled by desired morphology and balanced charge carrier mobilities with PBDBT-SF, suggesting that under a sufficiently high ΔHOMO, comprehensive considerations of the transport, film morphology, and energy levels are needed when designing new materials for high-performance OSCs.

Human Babesiosis Caused by a Babesia crassa-Like Pathogen: A Case Series.

Background: Human babesiosis is an emerging health problem in China. Methods: Babesia were identified in ticks, sheep, and humans in northeastern China using polymerase chain reaction (PCR) followed by genetic sequencing. We enrolled residents who experienced a viral-like illness after recent tick bite or were healthy residents. We defined a case using the definition for babesiosis developed by the US Centers for Disease Control and Prevention. Results: A Babesia crassa-like agent was identified in Ixodes persulcatus and Haemaphysalis concinna ticks using PCR followed by sequencing. The agent was characterized through phylogenetic analyses of the 18S rRNA gene, the ß-tubulin gene, and the internal transcribed spacer region. We tested sheep as a possible reservoir and found that 1.1% were infected with the B. crassa-like agent. We screened 1125 human participants following tick bites using B. crassa-specific PCR and identified 31 confirmed and 27 suspected cases. All the patients were previously healthy except for 1 with an ovarian tumor. Headache (74%), nausea or vomiting (52%), and fever (48%) were the most common clinical manifestations of confirmed cases. Six of 10 cases remained PCR positive for B. crassa-like infection 9 months after initial diagnosis. Asymptomatic infections were detected in 7.5% of 160 local residents. Conclusions: We identified B. crassa-like infection in people in northeastern China that caused mild to moderate symptoms. The possibility of more severe disease in immunocompromised patients and of transmission through the blood supply due to asymptomatic infections justifies further investigation of this reported infection.

Enhanced Efficiency of Dye-Sensitized Solar Cells Benefited from Graphene Modified by Ag Nanoparticles.

In this paper, graphene modified by Ag nanoparticles was successfully applied into dye sensitized solar cells. The morphologies and compositions of graphene and graphene-Ag nanoparticles were characterized by scanning electron microscope and energy dispersive X-ray spectroscopy. The optical and electrical properties were evaluated by UV-vis-NIR absorption spectroscopy, electrochemical impedance spectroscopy and current-voltage curve. The results indicated that the incorporation of graphene or graphene-Ag nanoparticles can improve the light absorption and decrease the charge recombination. The solar cells with graphene-Ag nanoparticles exhibited short-circuit current density of 14.34 mA cm-2, open-circuit voltage of 709 mV and conversion efficiency of 6.01%, which were higher than those of DSSCs with graphene or pure TiO2.

Borrelia miyamotoi Infections in Humans and Ticks, Northeastern China.

We conducted an investigation of Borrelia miyamotoi infections in humans and ticks in northeastern China. Of 984 patients reporting recent tick bites, 14 (1.4%) were found to be infected with B. miyamotoi by PCR and genomic sequencing. The 14 patients had nonspecific febrile manifestations, including fever, headache, anorexia, asthenia, and arthralgia. Rash, eschar, and regional lymphadenopathy were each observed in 1 patient. Four (28.6%) patients were hospitalized because of severe disease. B. miyamotoi was detected in 3.0% (19/627) of Ixodes persulcatus, 1 (2.8%) of 36 Haemaphysalis concinna, and none of 29 Dermacentor silvarum ticks. Phylogenetic analyses based on sequences of a nearly entire 16s rRNA gene, a partial flagellin gene, and the glycerophosphodiester phosphodiesterase gene revealed that B. miyamotoi identified in patients and ticks were clustered in the group of the Siberian type. These findings indicate that B. miyamotoi is endemic in northeastern China and its public health significance deserves further investigation.

Effects of metal ions on the structure and activity of a human anti-cyclin D1 single-chain variable fragment AD5.

Cyclin D1 has become a potential target for anti-tumor therapy. Recently, a novel human anti­cyclin D1 single­chain variable fragment (AD5) was identified, which demonstrated specific binding activity to cyclin D1 and exhibited anti­tumor effects. However, the detailed characteristics of AD5 remain unclear. In the present study, the structure and activity of AD5 in the presence of copper II (Cu2+) or iron III (Fe3+) metal ions was investigated by fluorescence spectroscopy, synchronous fluorescence and enzyme­linked immunosorbent assay. Cu2+ and Fe3+ were able to bind to AD5 and quench the fluorescence intensity of AD5 primarily by static quenching, which slightly altered the conformation of AD5 at temperatures of 293, 298 and 303 K; however, these temperatures demonstrated different effects on the activity of AD5. These results may be of value for the clinical application of anti-cyclin D1 single chain antibodies in the future.