First report of the family Ideoroncidae (Arachnida, Pseudoscorpiones) from China, with description of a new species.

Background: The pseudoscorpion genus Shravana Chamberlin, 1930, belonging to the family Ideoroncidae Chamberlin, 1930, currently contains 13 species. To date, no ideoroncid species has been recorded from China. New information: The family Ideoroncidae Chamberlin, 1930 is reported from China for the first time. A new species of the genus Shravana Chamberlin, 1930, collected from Xizang Autonomous Region, China, is described under the name of Shravanazhui Gao & Zhang, sp. nov. on the basis of both sexes. The finding of this new species expands the distribution range of this family in Asia.

MiR-29a-3p mediates phosphatase and tensin homolog and inhibits osteoarthritis progression.

Despite substantial progress in clinical trials of osteoarthritis (OA) gene therapy, the prevalence of OA is still on the rise. MiRNAs have a potential biomarker and therapeutic target for OA. OA cartilage and chondrosarcoma cells were studied to determine the role of miR-29a-3p and PTEN. OA cartilage and human chondrosarcoma cells (SW1353) were obtained. miR-29a-3p and PTEN signature expression was determined by RT-qPCR. The binding relationship between miR-29a-3p and PTEN was investigated by dual-luciferase reporter gene and western blot assay. TUNEL, immunohistochemistry, CCK-8, and flow cytometry were utilized to determine the proliferation and apoptosis of SW1353 cells. This study indicated downregulation of miR-29a-3p expression and upregulation of PTEN expression in human OA primary chondrocytes or OA tissue samples, compared with the normal cartilage cells or tissues. PTEN expression was negatively correlated with miR-29a-3p expression, and miR-29a-3p targeted PTEN mechanistically. miR-29a-3p reduced SW1353 cell activity and proliferation and promoted cell apoptosis. However, the aforementioned effects could be reversed by downregulating PTEN. miR-29a-3p can stimulate chondrocyte proliferation and inhibit apoptosis by inhibiting PTEN expression.

Fenofibrate Recognition and Gq Protein Coupling Mechanisms of the Human Cannabinoid Receptor CB1.

The G-protein-coupled human cannabinoid receptor 1 (CB1) is a promising therapeutic target for pain management, inflammation, obesity, and substance abuse disorders. The structures of CB1-Gi complexes in synthetic agonist-bound forms have been resolved to date. However, the commercial drug recognition and Gq coupling mechanisms of CB1 remain elusive. Herein, the cryo-electron microscopy (cryo-EM) structure of CB1-Gq complex, in fenofibrate-bound form, at near-atomic resolution, is reported. The structure elucidates the delicate mechanisms of the precise fenofibrate recognition and Gq protein coupling by CB1 and will facilitate future drug discovery and design.

The mechanisms and functions of TNF-α in intervertebral disc degeneration.

Low back pain (LBP) is one of the most common health problems in people's lives, which brings a massive burden to clinicians, and the leading cause of LBP is intervertebral disc degeneration (IDD). IDD is mainly caused by factors such as aging, mechanical stress, and lack of nutrition. The pathological mechanism of IDD is very complex, involving inflammatory response, cell metabolism disorder, and so on. Unfortunately, in the current treatment of IDD, only relieving symptoms as the primary means of relieving a patient's pain cannot effectively inhibit or reverse the progression of IDD. Tumor necrosis factor-α (TNF-α) is a multifunctional pro-inflammatory factor involved in many diseases' pathological processes. With the in-depth study of the pathological mechanism of IDD, more and more evidence has shown that TNF-α is an essential activator of IDD, which is related to the metabolic disorder, inflammatory responses, apoptosis, and other pathological processes of extracellular dissociation in the intervertebral disc. Therefore, anti-TNF-α therapy is an effective therapeutic target for alleviating IDD, especially in inhibiting extracellular matrix degradation and reducing inflammatory responses. This article reviews the pathological role of TNF-α in IDD and the latest research progress of TNF-α inhibitors in treating IDD.

ITGB3 promotes cisplatin resistance in osteosarcoma tumors.

OBJECTIVE: Osteosarcoma is the most malignant and common primary bone tumor with a high rate of recurrence that mainly occurs in children and young adults. Therefore, it is vital to facilitate the development of novel effective therapeutic means and improve the overall prognosis of osteosarcoma patients via a deeper understanding of the mechanisms of chemoresistance in osteosarcoma progression. METHODS: In this research, the relationship between ITGB3 and the clinical characteristics of patients was detected through analysis of publicly available clinical datasets. The expression of ITGB3 was analysis in collected human osteosarcoma tissues. In addition, the potential functions of ITGB3 in the cisplatin resistance of osteosarcoma cells were investigated in vitro and in tumor xenotransplantation. Finally, the molecular mechanism of ITGB3 in the progression and recurrence of osteosarcoma were explored via transcriptome analysis. RESULTS: ITGB3 was identified as a potential regulator of tumorigenicity and cisplatin resistance in relapsed osteosarcoma. Furthermore, the decreased osteosarcoma cell proliferation and migration ability in ITGB3 knockout osteosarcoma cells were related to increased apoptosis and slowing cell cycle progression. In addition, ITGB3 had a positive correlation with cisplatin resistance in cells and tumor xenografts in mice. Accordingly, ITGB3 performed the functions of proliferation and cisplatin resistance in osteosarcoma through the MAPK and VEGF signaling pathways. CONCLUSION: Our results will contribute to a better understanding of the function and mechanism of ITGB3 in osteosarcoma cisplatin resistance and provide a novel therapeutic target to decrease cisplatin resistance and tumor recurrence in osteosarcoma patients.

Mitochondrion-targeting near-infrared fluorescent probe for detecting intracellular nanomolar level hydrogen sulfide with high recognition rate.

Hydrogen sulfide (H2S) typically plays biphasic biological roles in living organisms with subnormal H2S exerting cytoprotective effects such as participating in cardioprotective signaling pathways while H2S with higher-than-normal concentrations in localized tissues acting the opposite way such as inhibiting mitochondrial respiration. Such concentration-dependent biological and pathological roles of H2S with the wide involvement of mitochondria and the elusive feature of H2S definitely highlight the vital significance of fast and precise estimation of the physiological level of H2S in specific microenvironments, particularly within cellular mitochondria. In this work, we developed a new type of fluorescent probe (QcyCHO) featured with H2S-triggered off-to-on near-infrared (NIR) fluorescence conversion within ~ 10 min, limit of detection (LOD) down to 8.3 nM, and high recognition specificity over other similarly interfering species. The ideal mitochondrion-targeting ability, high recognition specificity over typical interfering substances and other physiologically relevant species, and the ability for mapping intracellular H2S in living cells of QcyCHO probe were also unequivocally confirmed, which imply its potential for shedding light on the biology of H2S and therapeutic development in H2S-associated diseases by identifying the specific physiological stimuli inducing H2S production and determining the levels of H2S at the location and time of stimulation.

A long-wavelength turn-on fluorescent probe for intracellular nanomolar level peroxynitrite sensing with second-level response.

As a typical kind of endogenous reactive nitrogen species, peroxynitrite (ONOO-) is believed heavily involved in the pathogenesis of many diseases such as inflammation, neurodegenerative conditions, and cardiovascular disorders. Precisely estimating ONOO- level in cell compartments is crucial for unraveling the biological relevance of ONOO- and enabling effective control of ONOO--associated pathogenicity but suffers from serious difficulty owing to the daunting elusive features of ONOO-, namely nanomolar level physiological concentration and millisecond level biological half-life. A new fluorescent probe capable of detecting ONOO- with limit of detection down to 1.2 nM, response time less than 1s, and high recognition specificity over other similarly interfering species was developed in this work. For the probe constructed by conjugating an isatin moiety with an electron-withdrawing tricyanofuran (TCF) moiety, the former enabled a highly selective ONOO--mediated oxidative decarbonylation reaction while the latter significantly improved the electrophilicity of the 3-position carbonyl group of isatin moiety and therefore accelerate the ONOO--mediated nucleophilic attack, which eventually enabled prompt and efficient recognition reaction. For the decarbonylated product featured with a released primary aniline moiety, TCF acted as an acceptor for enabling an intramolecular charge transfer (ICT) process and the remarkable change in electronic feature upon reaction with ONOO-, which generated turn-on fluorescence with large contrast and therefore the basis for ONOO- sensing. The cell fluorescence imaging performed in this work definitely verified the capability of the probe for mapping intracellular ONOO-, despite the daunting elusive features of such physiological species.

Effects of feeding level and C/N ratio on water quality, growth performance, immune and antioxidant status of Litopenaeus vannamei in zero -water exchange bioflocs-based outdoor soil culture ponds.

Two trials were conducted as follows: the first trial was a 90-day experiment to determine the effects of reducing feeding level on shrimp status; the second trial (90 days) is based on the first trial to explore the suitable C/N ratio of biological flocs for shrimp culture in outdoor soil ponds. Results showed that the BFV levels increased gradually and then tended to be stable in the treatment groups. Concentrations of TAN and NO2-N were maintained low level in each treatment pond during experimental period. The final body weight, biology body length and yield of the shrimp in each trial with no significantly different (P > 0.05) while food coefficient and THC of the shrimp in 70% feeding level and C/N12 treatment were slightly lower than in the 100% feeding level and C/N16 treatment respectively (p < 0.05). The antibacterial activity and bacteriolytic activity in C/N16 treatment group were higher than in C/N12 (p < 0.05), while there were no significant difference between the two feeding levels (70%,100%) (P > 0.05). The shrimp in 70% feeding level and C/N12 treatment had the higher T-AOC in both the plasma and the hepatopancreas when compared with 100% feeding level and C/N16 treatment group (p < 0.05). The SOD activity of plasma in 70% treatment group was higher than in 100% (p < 0.05), while it was no significant difference between the two C/N ratios (12,16) in both the plasma and the hepatopancreas (P > 0.05). The effects of two feeding levels and C/N ratios on the GSH level and the ratio of GSH/GSSG in the plasma and the hepatopancreas of shrimp showed no significant difference (P > 0.05). The results showed that 70% feeding level and C/N12 ratio could provide adequate nutrition for shrimp to maintain a normal physical health status with the presence of bioflocs.

A single-chromophore-based agent enables rapid sensing of intracellular hypochlorous acid and in-situ photodynamic therapy to cancer cells.

A single-chromophore-based photoactive agent (MB-DOPA) capable of rapid sensing of nanomolar hypochlorous acid (HOCl) and in-situ generating photocytotoxicity to cancer cells was developed using dopamine moiety as the recognition unit and methylene blue (MB) moiety as the fluorescence signaling unit. Specifically, HOCl triggered conversion of the nonfluorescent MB-DOPA to MB enabling far-red fluorescence emission (λmax ∼ 683 nm) and additional ability to photogenerate 1O2 species. Owing to the catechol nature of dopamine characterized with strong electron-donating property, MB-DOPA underwent HOCl-mediated conversion with response time of ∼20 s and a strong fluorescence OFF-to-ON contrast by a factor of more than 3000. The preliminary bioimaging results confirmed the intracellular HOCl sensing ability of MB-DOPA and the in-situ photodynamic therapy (PDT) effectiveness for inducing massive apoptosis of cancer cells. The figure of merits of MB-DOPA, including ability for sensing of nanomolar HOCl with high specificity, rapid response, practicality for intracellular fluorescence imaging, and the in-situ generation of 1O2 for killing tumor cells, is expected to enable diagnosis of early-stage oncogenesis based on the highly specific detection of abnormal HOCl levels in the transformed cells and the simultaneous treatment in biomedical applications.

A Turn-On Fluorescent Probe for Detection of Sub-ppm Levels of a Sulfur Mustard Simulant with High Selectivity.

A new type of fluorescent probe capable of detecting a sulfur mustard (SM) simultant at a concentration of 1.2 µM in solution and 0.5 ppm in the gas phase has been developed. Owing to its molecular structure with a thiocarbonyl component and two piperidyl moieties integrated into the xanthene molecular skeleton, this probe underwent a highly selective nucleophilic reaction with the SM simultant and generated a thiopyronin derivative emitting intensive pink fluorescence. The distinct difference in electronic structure between the probe and thiopyronin derivative generated a marked shift of the absorption band from 445 to 567 nm, which enabled an optimal wavelength propitious for exciting the thiopyronin derivative but adverse to the probe. Such efficient separation of the excitation wavelength and tremendous increase in fluorescence quantum yield, from less than 0.002 to 0.53, upon conversion from the probe to the thiopyronin derivative, jointly led to a distinct contrast in the beaconing fluorescence signal (up to 850-fold) and therefore the unprecedented sensitivity for detecting SM species.

Analysis of the genetic relationships and diversity among 11 populations of Xanthoceras sorbifolia using phenotypic and microsatellite marker data

Background: Assessments of genetic diversity are essential for germplasm characterization and exploitation. Molecular markers are valuable tools for exploring genetic variation and identifying germplasm. They play key roles in a Xanthoceras sorbifolia breeding program. Results: We analyzed the genetic diversity of populations of this species using 23 simple sequence repeat (SSR) loci and data on kernel oil content. The 11 populations included in the study were distributed across a large geographic range in China. The kernel oil content differed significantly among populations. The SSR marker analysis detected high genetic diversity among the populations. All SSRs were polymorphic, and we identified 80 alleles across the populations. The number of alleles at each locus ranged from two to six, averaging 3.48 per primer pair. The polymorphism information content values ranged from 0.35 to 0.70, averaging 0.51. Expected heterozygosity, observed heterozygosity, and Shannon's information index calculations detected large genetic variations among populations of different provenance. The high average number of alleles per locus and the allelic diversity observed in the set of genotypes analyzed indicated that the genetic base of this species was relatively wide. The statistically significant positive correlation between genetic and geographic distances suggested adaptations to local conditions. Conclusions: Microsatellite markers can be used to efficiently distinguish X. sorbifolia populations and assess their genetic diversity. The information we have provided will contribute to the conservation and management of this important plant genetic resource.

Photoswitchable fluorescent nanoparticles and their emerging applications.

Although fluorescence offers ultrasensitivity, real-world applications of fluorescence techniques encounter many practical problems. As a noninvasive means to investigate biomolecular mechanisms, pathways, and regulations in living cells, the intrinsic heterogeneity and inherent complexity of biological samples always generates optical interferences such as autofluorescence. Therefore, innovative fluorescence technologies are needed to enhance measurement reliability while not compromising sensitivity. In this review, we present current strategies that use photoswitchable nanoparticles to address these real-world challenges. The unique feature in these photoswitchable nanoparticles is that fundamental molecular photoswitches are playing the critical role of fluorescence modulation rather than traditional methods like modulating the light source. As a result, new innovative technologies that have recently emerged include super-resolution imaging, frequency-domain imaging, antiphase dual-color correlation, etc. Some of these methods improve imaging resolution down to the nanometer level, while others boost the detection sensitivity by orders of magnitude and confirm the nanoparticle probes unambiguously. These enhancements, which are not possible with non-photoswitching molecular probes, are the central topics of this review.