An Intramolecular Rotor-Bridged Dimeric Cyanine Photothermal Transducer for Efficient Near-Infrared II Fluorescence Imaging-Guided Mitochondria-Targeted Phototherapy.

Near-infrared (NIR) heptamethine cyanine (HCy) dyes are promising photothermal transducers for image-guided cancer treatment owing to their prominent photophysical properties and high photothermal conversion ability. However, HCy photothermal transducers usually have poor photostability due to degradation induced by the self-generated reactive oxygen species. Herein, a novel mitochondria-targeting dimeric HCy dye, named dimeric oBHCy, is rationally designed, exhibiting strong near-infrared II (NIR-II) fluorescence emission, high photothermal conversion efficiency (PCE), and excellent photostability. The large π-conjugation and drastic intramolecular motion of the diphenol rotor in the dimeric oBHCy enhance the nonradiative energy dissipation and suppress the intersystem crossing process, thereby achieving a high PCE (49.2%) and improved photostability. Impressively, dimeric oBHCy can precisely target mitochondria and induce mitochondrial damage upon NIR light irradiation. Under the guidance of in vivo NIR-II fluorescence imaging, efficient NIR light-activated photothermal therapy of 4T1 breast tumors is accomplished with a tumor inhibitory rate of 96% following a single injection of the dimeric oBHCy. This work offers an innovative strategy for designing cyanine photothermal transducers with integrated NIR-II fluorescence and photothermal properties for efficient cancer theranostics.

An Active Self-Mitochondria-Targeting Cyanine Immunomodulator for Near-Infrared II Fluorescence Imaging-Guided Synergistic Photodynamic Immunotherapy.

Photodynamic therapy targeting mitochondria represents a promising therapeutic strategy for fighting diverse types of cancers. However, the currently available photosensitizers (PSs) suffer from insufficient therapeutic potency, limited mitochondria delivery efficiency, and the inability to treat invisible metastatic distal cancers. Herein, an active self-mitochondria-targeting heptapeptide cyanine (HCy) immunomodulator (I2HCy-QAP) is reported for near-infrared II (NIR-II) fluorescence imaging-guided photodynamic immunotherapy of primary and distal metastatic cancers. The I2HCy-QAP is designed by introducing a quaternary ammonium salt with a phenethylamine skeleton (QAP) into the iodinated HCy photosensitizer. The I2HCy-QAP can precisely target mitochondria due to the lipophilic cationic QAP unit, present strong NIR-II fluorescence tail emission, and effectively generate singlet oxygen 1O2 under NIR laser irradiation, thereby inducing mitochondria-targeted damages and eliciting strong systemic immunogenic cell death immune responses. The combination of the I2HCy-QAP-mediated photodynamic immunotherapy with anti-programmed death-1 antibody therapy achieves remarkable therapeutic efficacy against both primary and distal metastatic cancers with significant inhibition of lung metastasis in a triple-negative breast cancer model. This work provides a new concept for designing high-performance NIR emissive cyanine immunomodulators for NIR-II fluorescence-guided photodynamic immunotherapy.

[Optimization of processing technology of bark of Ilicis Rotundae Cortex based on quality by design concept].

Based on the concept of quality by design(QbD), this study optimized the processing technology of Ilicis Rotundae Cortex. According to the processing method and ingredient requirements of Ilicis Rotundae Cortex in the Chinese Pharmacopoeia, the content of syringin and pedunculoside, alcohol extract, fragmentation rate, and moisture content were taken as the critical quality attributes(CQAs). The soaking time, moistening time, and drying time were taken as critical process parameters(CPPs) by single factor tests. The weight coefficients of CQAs were determined by the analytic hierarchy process(AHP)-entropy weighting method, and the comprehensive score was calculated. With the comprehensive score as the response value, Box-Behnken design was employed to establish a mathematical model between CPPs and CQAs, and the design space for the processing of Ilicis Rotundae Cortex was built and verified. The results of ANOVA showed that the mathematical model had the P value below 0.05, the lack of fit greater than 0.05, adjusted R~2=0.910 5, and predicted R~2=0.831 0, which indicated that the proposed model had statistical significance and good prediction performance. Considering the factors in production, the best processing conditions of Ilicis Rotundae Cortex were decoction pieces of about 1 cm soaking for 1 h, moistening for 4 h, and drying at 60-70 ℃ in a blast drier for 2 h. The optimized processing technology of Ilicis Rotundae Cortex was stable and feasible, which can provide a reference for the standardized preparation and stable quality of Ilicis Rotundae Cortex.

Soybean balanced the growth and defense in response to SMV infection under different light intensities.

Light is essential for the growth and defense of soybean. It is not clear how soybeans adjust their defenses to different light environments with different cropping patterns. The mechanism of soybean response to Soybean mosaic virus (SMV) infection under different light intensities was analyzed by RNA-seq sequencing method. Enrichment analysis illustrated that most defense-related genes were down-regulated in the dark and the shade, and up-regulated under hard light and normal light. Soybean can resist SMV infection mainly by activating salicylic acid signaling pathway. Light is essential for activating salicylic acid defense signaling pathways. With the increase of light intensity, the oxidative damage of soybean leaves was aggravated, which promoted the infection of virus. When light was insufficient, the growth of soybean was weak, and the plant-pathogen interaction pathway, MAPK pathway and hormone defense pathway in infected soybean was inhibited. Under hard light, some defense genes in infected soybean were down-regulated to reduce the degree of oxidative damage. The expression of differentially expressed genes was verified by real-time fluorescence quantitative RT-PCR. In order to adapt to the change of light intensity, soybean balanced allocation of resources between growth and defense through a series regulation of gene expression. The results of this study will provide a theoretical basis for the research of SMV resistance in intercropping soybean.

3% nebulized hypertonic saline versus normal saline for infants with acute bronchiolitis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: This study evaluated the efficacy and safety of 3% nebulized hypertonic saline (NHS) in infants with acute bronchiolitis (AB). METHODS: We systematically searched the PUBMED, EMBASE, Cochrane Library, China National Knowledge Infrastructure Database, WANFANG, and VIP databases from inception to June 1, 2022. We included randomized controlled trials comparing NHS with 0.9% saline. Outcomes included the length of hospital stay (LOS), rate of hospitalization (ROH), clinical severity score (CSS), rate of readmission, respiratory distress assessment instrument, and adverse events. RevMan V5.4 software was used for statistical analysis. RESULTS: A total of 27 trials involving 3495 infants were included in this study. Compared to normal saline, infants received 3% NHS showed better outcomes in LOS reduction (MD = -0.60, 95% CI [-1.04, -0.17], I2 = 92%, P = .007), ROH decrease (OR = 0.74, 95% CI [0.59, 0.91], I2 = 0%, P = .005), CSS improvement at day 1 (MD = -0.79, 95% CI [-1.23, -0.34], I2 = 74%, P < .001), day 2 (MD = -1.26, 95% CI [-2.02, -0.49], I2 = 91%, P = .001), and day 3 and over (MD = -1.27, 95% CI [-1.92, -0.61], I2 = 79%, P < .001), and respiratory distress assessment instrument enhancement (MD = -0.60, 95% CI [-0.95, -0.26], I2 = 0%, P < .001). No significant adverse events related to 3% NHS were observed. CONCLUSION: This study showed that 3% NHS was better than 0.9% normal saline in reducing LOS, decreasing ROH, improving CSS, and in enhancing the severity of respiratory distress. Further studies are needed to validate these findings.

Cu-Catalyzed C-H Alkenylation of Benzoic Acid and Acrylic Acid Derivatives with Vinyl Boronates.

An efficient Cu-catalyzed C-H alkenylation with acyclic and cyclic vinyl boronates was realized for the first time under mild conditions. The scope of the vinyl borons and the compatibility with functional groups including heterocycles are superior than Pd-catalyzed C-H coupling with vinyl borons, providing a reliable access to multisubstituted alkenes and dienes. Subsequent hydrogenation of the product from the internal vinyl borons will lead to installation of secondary alkyls.

Cu-Mediated Amination of (Hetero)Aryl C-H bonds with NH Azaheterocycles.

Direct synthesis of N-(hetero)arylated heteroarenes has been realized through Cu-mediated C-N coupling of NH azaheterocycles with aryl C-H bonds under aerobic conditions. This method features a broad scope of both heterocyclic arenes (pyridine, quinoline, pyrazole, imidazole, furan, thiophene, benzofuran, and indole) and NH azaheterocycles (imidazole, pyrazole, indole, azindole, purine, indazole, benzimidazole, pyridone, carbazole), providing a versatile method for the synthesis of pharmaceutically important N-(hetero)arylated heteroarenes. The versatility of this reaction was further demonstrated through late-stage modification of marketed drugs and the synthesis of a key intermediate for accessing a class of angiotensin II receptor 1 antagonists.

AidB, a Novel Thermostable N-Acylhomoserine Lactonase from the Bacterium Bosea sp.

Many Gram-negative bacteria employ N-acylhomoserine lactones (AHLs) as quorum-sensing (QS) signal molecules to regulate virulence expression in a density-dependent manner. Quorum quenching (QQ) via enzymatic inactivation of AHLs is a promising strategy to reduce bacterial infections and drug resistance. Herein, a thermostable AHL lactonase (AidB), which could degrade different AHLs, with or without a substitution of carbonyl or hydroxyl at the C-3 position, was identified from the soil bacterium Bosea sp. strain F3-2. Ultrahigh-performance liquid chromatography analysis demonstrated that AidB is an AHL lactonase that hydrolyzes the ester bond of the homoserine lactone (HSL) ring. AidB was thermostable in the range 30 to 80°C and showed maximum activity after preincubation at 60°C for 30 min. The optimum temperature of AidB was 60°C, and the enzyme could be stably stored in double-distilled water (ddH2O) at 4°C or room temperature. AidB homologs were found only in Rhizobiales and Rhodospirillales of the Alphaproteobacteria AidB from Agrobacterium tumefaciens and AidB from Rhizobium multihospitium (with amino acid identities of 50.6% and 52.8% to AidB, respectively) also showed thermostable AHL degradation activity. When introduced into bacteria, plasmid-expressed AidB attenuated pyocyanin production by Pseudomonas aeruginosa PAO1 and the pathogenicity of Pectobacterium carotovorum subsp. carotovorum Z3-3, suggesting that AidB is a potential therapeutic agent by degrading AHLs.IMPORTANCE A quorum-sensing system using AHLs as the signal in many bacterial pathogens is a critical virulence regulator and an attractive target for anti-infective drugs. In this work, we identified a novel AHL lactonase, AidB, from a soil bacterial strain, Bosea sp. F3-2. The expression of aidB reduced the production of AHL signals and QS-dependent virulence factors in Pseudomonas aeruginosa and Pectobacterium carotovorum The homologs of AidB with AHL-degrading activities were found only in several genera belonging to the Alphaproteobacteria Remarkably, AidB is a thermostable enzyme that retained its catalytic activity after treatment at 80°C for 30 min and exhibits reliable storage stability at both 4°C and room temperature. These properties might make it more suitable for practical application.

The reproductive health indices and sex hormone levels in middle-aged and elderly Chinese men.

OBJECTIVE: The aim of this study was to analyze the age-related recession trajectory of reproductive health indices in middle-aged and elderly Chinese men. METHODS: A population-based cross-sectional study was conducted in Jiashan County, Zhejiang in 2012. Healthy men between 40 and 80 years of age were considered eligible for the study. Physical examination and the sex hormones were measured. The subjects were assessed based on the 5-item version of the International Index of Erectile Function (IIEF-5) for Erectile Dysfunction (ED), and Aging Males' Symptoms (AMS) scale for Symptomatic Late-Onset Hypogonadism (SLOH). RESULTS: TG showed a decrease at age 60 years. Testis volume and TT did not show significant difference among the four age groups; cFT began to decrease at age 50 years and Bio-T decreased faster at age 50 years. SHBG and LH increased faster at age 50 and 70 years, respectively. IIEF5 score decrease faster at age 60 years. AMS scores increased faster at age 70 years. With the increase in age, the symptoms of ED and SLOH became severer. CONCLUSION: Different indices on reproductive health of men showed turning points at different ages. At first, androgenic sex hormones decreased faster, and then erectile dysfunction got severer, and the last overall male syndromes declined.

Identification and RNA Interference of the Pheromone Biosynthesis Activating Neuropeptide (PBAN) in the Common Cutworm Moth Spodoptera litura (Lepidoptera: Noctuidae).

Spodoptera litura F. is one of the most destructive insect pests of many agricultural crops and notorious for developing insecticide resistance. Developing environmental friendly control methods such as novel pheromone and RNAi-related control strategies is imperative to control this pest. In the present study, the full-length cDNA encoding the diapause hormone and pheromone biosynthesis activating neuropeptide (DH-PBAN) was identified and characterized in S. litura. This 809-bp transcript contains a 573-nucleotide ORF encoding a 191-amino acid protein, from which five putative neuropeptides, including PBAN, DH, and α-, ß-, and γ-subesophageal ganglion neuropeptides, were derived. Phylogenetic analysis showed that both the whole protein and each of the five neuropeptides have high similarities to those of DH-PBANs from other insect orders particularly Lepidoptera. Females treated with TKYFSPRLamide (the active core fragment of PBAN) produced significantly more four types of pheromone compounds (A; B; C; D) than controls. RNA interference by injection of PBAN dsRNA significantly reduced the relative expression levels of this gene in adult females (approximately reduced by 60%). As a consequence, females treated with PBAN dsRNA produced significantly less four types of pheromone compounds (A; B; C; D) than controls. These results suggest that PBAN function in activating sex pheromone biosynthesis and the RNAi of DH-PBAN gene can be induced by the injection of dsRNA into the body cavity in S. litura. This study suggests the possibility of novel pheromone-related pest control strategies based on RNAi techniques.

Draft Genome Sequence of the Bacterium Lysobacter capsici X2-3, with a Broad Spectrum of Antimicrobial Activity against Multiple Plant-Pathogenic Microbes.

Lysobacter capsici strain X2-3 was isolated from the wheat rhizosphere in China and exhibits a remarkable capacity to inhibit the growth of multiple pathogens. Here, we report the draft genome sequence of L. capsici strain X2-3 in China.

Female and male moths display different reproductive behavior when facing new versus previous mates.

Multiple mating allows females to obtain material (more sperm and nutrient) and/or genetic benefits. The genetic benefit models require sperm from different males to fertilize eggs competitively or the offspring be fathered by multiple males. To maximize genetic benefits from multiple mating, females have evolved strategies to prefer novel versus previous mates in their subsequent matings. However, the reproductive behavior during mate encounter, mate choice and egg laying in relation to discrimination and preference between sexes has been largely neglected. In the present study, we used novel and previous mate treatments and studied male and female behavior and reproductive output in Spodoptera litura. The results of this study do not support the sperm and nutrient replenishment hypotheses because neither the number of mates nor the number of copulations achieved by females significantly increased female fecundity, fertility and longevity. However, females showed different oviposition patterns when facing new versus previous mates by slowing down oviposition, which allows the last male has opportunities to fertilize her eggs and the female to promote offspring diversity. Moreover, females that have novel males present called earlier and more than females that have their previous mates present, whereas no significant differences were found on male courtship between treatments. These results suggest that S. litura females can distinguish novel from previous mates and prefer the former, whereas males generally remate regardless of whether the female is a previous mate or not. In S. litura, eggs are laid in large clusters and offspring competition, inbreeding and disease transfer risks are thus increased. Therefore, offspring diversity should be valuable for S. litura, and genetic benefits should be the main force behind the evolution of female behavioral strategies found in the present study.

[Erectile dysfunction in men with lower urinary tract symptoms].

OBJECTIVE: To investigate the incidence of erectile dysfunction (ED) in men with lower urinary tract symptoms (LUTS) and the correlation between LUTS and ED. METHODS: We enrolled 1 000 men aged 40 - 80 years with regular sex partners, evaluated their erectile function using IIEF-5, and investigated LUTS among them by International Prostate Symptom Score (IPSS). We studied the relationship between ED and LUTS by univariate conditional Logistic regression analysis. RESULTS: LUTS were found in 42.81% of the men investigated (426/995), and ED in 76.18% of the subjects (758/995) and 82.16% of those with LUTS (350/426). Logistic regression analysis revealed a significant relation of ED with aging and LUTS (P < 0.01). CONCLUSION: The The incidence of ED is high in men with LUTS and increases with aging and the severity of LUTS.

Therapeutic potential of EGCG on acute renal damage in a rat model of obstructive nephropathy.

As a major active component in green tea, (-)-epigallocatechin 3-O-gallate (EGCG) has many anti-oxidative activities. This study investigated whether intraperitoneal administration of EGCG was capable of suppressing oxidative stress in rats with unilateral ureteral obstruction (UUO) and probed the potential mechanisms involved. In total, 150 adult male rats were randomly divided into 5 groups (n=30 each): the control group (group N); the unilateral ureteral obstruction (UUO) group (group C), where the unilateral ureter was ligated resulting in an obstructive nephropathy model; and the EGCG group (group T), following unilateral ureteral ligation, rats were intraperitoneally injected with EGCG at a dosage of 2.5 (T1), 5 (T2) and 10 mg/kg/day (T3). Each group of rats was sacrificed 72 h after surgery. We evaluated the effects of EGCG on the reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione in the renal tissue of rats. Immunohistochemistry and western blot analysis were applied to detect nuclear factor erythoid-derived 2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) protein expression. Real-time PCR was performed to detect the mRNA levels of Nrf2 and γ-GCS. Changes in renal ultrastructure were also observed using electron microscopy. There was no significant difference in GSH, and compared with group N, ROS, GSSG and total GSH levels were much higher in the T groups (p<0.01), while much lower than those of group C (p<0.01). Protein levels of Nrf2 and γ-GCS and the mRNA levels of Nrf2 and γ-GCS notably increased in EGCG-treated rats (all p<0.05). Furthermore, electron microscopy showed that renal ultrastructure was improved in the treatment groups. Our findings suggest that, resulting from suppression of oxidative stress influenced by free radicals, EGCG exerts a protective effect on rats with obstructive nephropathy, and this anti-oxidative effect may be partly induced by activating the Nrf2 signaling pathway.

[Effect of adenovirus-mediated tissue factor pathway inhibitor gene transfer on apoptosis of rat vascular smooth muscle cells].

OBJECTIVE: Previous studies showed potential role of tissue factor pathway inhibitor (TFPI) on attenuating restenosis, we investigated the effect of TFPI gene transfer on vascular smooth muscle cells (VSMCs) apoptosis. METHODS: Human TFPI recombinant adenovirus or LacZ recombinant adenovirus or PBS were transferred to rat aortic VSMCs respectively in vitro. RT-PCR was used to detect the expression of exogenous TFPI gene. VSMCs were examined by cell counting and MTT. Apoptosis of VSMCs was detected by flow cytometry, TUNEL and electron microscope at different time after gene transfer. RESULTS: mRNA expression of TFPI was detected in VSMCs at the 3rd day after gene transfer. Cell numbers and absorbance value in Ad-TFPI group were similar as those in Ad-LacZ and PBS groups at the 1st, 3rd and 5th day but significantly lower at the 7th day (P<0.05) after gene transfer. The apoptosis rates in Ad-TFPI group tested by flow cytometry were all significant higher than those in Ad-lacZ groups at each time point. The positive rates in Ad-TFPI group determined by TUNEL were significant higher than those in Ad-LacZ groups at 3rd (10.82% +/- 1.57% vs. 3.46% +/- 0.93%), 5th and 7th (16.95% +/- 2.01% vs. 5.11% +/- 1.29%, all P<0.05) day post gene transfer. Electron microscope evidenced cell contracting, cytoplasm condensing, lightly swelled mitochondria, nucleus pyknosis and apoptotic body formation after gene transfer in Ad-TFPI group which were not shown in cells of LacZ and PBS groups. CONCLUSION: TFPI gene transfer could induce apoptosis in rat VSMCs which might be one of the mechanisms responsible for its beneficial effect on restenosis inhibition after angioplasty.

[Diversity and niche of soil moniliaceous hyphomycetes in Taibai Mountain].

Sixteen genera of soil moniliaceous hyphomycetes were isolated from 40 soil samples collected from the southern and northern slopes of Taibai Mountain, and the indices Shannon-Wiener diversity index, evenness, niche breadth, and niche overlap were used to analyze the community structure and niche of soil moniliaceous hyphomycetes in different forest types on the southern and northern slopes of Taibai Mountain. The results showed that the distribution of soil moniliaceous hyphomycetes on the study area had an obvious environmental gradient pattern. Altitude and forest type were the main determinants of the fungal community distribution. The species richness and diversity index of soil moniliaceous hyphomycetes decreased significantly with increasing altitude, but the community evenness represented an increasing trend. Among the genera of soil moniliaceous hyphomycetes, Penicillium, Aspergillus, Verticillium, Paecilomyces and Acremonium had larger niche width and greater niche overlap with other genera, suggeting that these genera had wide distribution on the southern and northern slopes of Taibai Mountain. As for Trichothecium, Gliocladium and Metarhizium, their niche width was narrower, and their niche overlap with other genera was smaller, indicating that the distribution of these genera was more affected by altitude and vegetation, with the occurrence only in special forest types.

[Concepts of ontology-based neuroinformatics and their relations].

OBJECTIVE: To supply good information integration, knowledge representation, text mining, intellectual education and data sharing services by setting up neuroinformatics ontology. METHODS: By analyzing the structures and contents of current ontologies in the biomedical field, such as UMLS, Gene Ontology, Cancer Ontology, Anatomy Ontology, Disease Ontology and Drug Ontology, the concepts and their relationships of neuroinformatics were discussed and the design principles, standards and norms, building methods and basic procedures of multi-level concept semantic networks-based neuroinformatics ontology constructed by Protege-OWL tool were presented in this article. RESULTS: A multi-level concept semantic network-based OWL (web ontology language) neuroinformatics ontology was built. CONCLUSION: The neuroinformatics ontology can bring about explicit definitions of concepts and their relationships in the field of neuroinformatics from different formal models, build clear theoretical framework for neuroinformatics, achieve a common understanding of related field knowledge and supply good services of information integration, knowledge representation, text mining, intelligent education and data sharing.

Diversity analysis of soil dematiaceous hyphomycetes from the Yellow River source area: I.

Twenty-four soil samples of eight ecosystem-types around the Yellow River source area were investigated for the number and specific composition of soil dematiaceous hyphomycetes by dilution plate technique. And then the co-relationship between genus species of soil dematiaceous hyphomycetes and ecosystem-types was analyzed. The results show that the amount and species distribution of soil dematiaceous hyphomycetes had an obvious variability in different ecosystem-types, and that the dominant genus species varied in the eight ecosystem-types studied, with Cladosporium being the dominant genus in seven of the eight ecosystem-types except wetland. The index of species diversity varied in different ecosystem-types. The niche breadth analysis showed that Cladosporium had the highest niche breadth and distributed in all ecosystem-types, while the genera with a narrow niche breadth distributed only in a few ecosystem-types. The results of niche overlap index analysis indicated that Stachybotrys and Torula, Doratomyces and Scolecobasidium, Cladosporium and Chrysosporium had a higher niche overlap, whereas Arthrinium and Gliomastix, Phialophora and Doratomyces, Oidiodendron and Ulocladium had no niche overlap.