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A series of dinuclear Ir(III) complexes have been constructed for enhanced photodynamic and photothermal therapy (PDT and PTT) for cisplatin-resistant non-small-cell lung cancer. They enter cells via caveolar endocytosis, target mitochondria but not nuclear, generate both singlet oxygen and superoxide anion, and release heat when exposed to infrared (IR) irradiation, thus inducing reactive oxygen species (ROS)-associated cell disruption and thermal ablation. The IR-generated ROS can further activate caspases, triggering apoptosis. Additionally, the ROS deplete intracellular glutathione, lead to lipid peroxidation, and induce ferroptosis. The selected dinuclear Ir(III) complex Ir4 can completely eradicate cisplatin-resistant non-small-cell lung tumor in 75% of the phototreated mice with an inhibition rate of tumor growth above 96%. They have an extremely low toxicity to normal liver and kidney cells. After therapy, metal was not detected in the collected organs of mice except the tumor. A synergistic therapy consisting of potent IR-driven PDT and mild PTT accomplished by single-molecule dinuclear Ir(III) complexes is highly significant for the safe and effective PDT of large, deep-seated tumors as well as for overcoming the complicated drug resistance mechanisms of cancer.

Pregnant women with gestational diabetes mellitus undergoing glucocorticoid treatment to prevent neonatal respiratory distress syndrome could have increased glucose level. We performed a retrospective study and reviewed gestational diabetic women who received an intramuscular dexamethasone injection (6 mg, every 12 hours, 4 times) in our hospital between December 2018 and June 2020. Eligible pregnant women were assigned to the study group (with simultaneous subcutaneous insulin detemir injection, 2-4 units per day) or the control group (without insulin detemir injection). The fasting and 2-hour postprandial blood glucose levels were measured before and on days 1, 2, and 3 after the insulin detemir injection. The changes in their blood glucose levels were compared before and after the drug administrations as well as between the 2 groups. A total of 104 pregnant women were analyzed, including 48 women in the study group and 56 women in the control group. The blood glucose levels increased, with the peak levels occurring on the next day, after the dexamethasone administration in both groups. Compared with the control group, the study group had lower 2-hour postprandial blood glucose levels on days 2 and 3 after the insulin detemir injection (P < .05). There were no statistically significant differences in the fasting blood glucose levels between the 2 groups. Dexamethasone administration increased the blood glucose levels in the pregnant women with gestational diabetes mellitus. A short-course of low-dose insulin detemir administration effectively lowered the blood glucose levels in these women., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2025 the Author(s). Published by Wolters Kluwer Health, Inc.)

Land use change threatens global biodiversity and compromises ecosystem functions, including pollination and food production. Reduced taxonomic α-diversity is often reported under land use change, yet the impacts could be different at larger spatial scales (i.e., γ-diversity), either due to reduced β-diversity amplifying diversity loss or increased β-diversity dampening diversity loss. Additionally, studies often focus on taxonomic diversity, while other important biodiversity components, including phylogenetic diversity, can exhibit differential responses. Here, we evaluated how agricultural and urban land use alters the taxonomic and phylogenetic α-, β-, and γ-diversity of an important pollinator taxon-bees. Using a multicontinental dataset of 3117 bee assemblages from 157 studies, we found that taxonomic α-diversity was reduced by 16%-18% in both agricultural and urban habitats relative to natural habitats. Phylogenetic α-diversity was decreased by 11%-12% in agricultural and urban habitats. Compared with natural habitats, taxonomic and phylogenetic β-diversity increased by 11% and 6% in urban habitats, respectively, but exhibited no systematic change in agricultural habitats. We detected a 22% decline in taxonomic γ-diversity and a 17% decline in phylogenetic γ-diversity in agricultural habitats, but γ-diversity of urban habitats was not significantly different from natural habitats. These findings highlight the threat of agricultural expansions to large-scale bee diversity due to systematic γ-diversity decline. In addition, while both urbanization and agriculture lead to consistent declines in α-diversity, their impacts on β- or γ-diversity vary, highlighting the need to study the effects of land use change at multiple scales., (© 2025 John Wiley & Sons Ltd.)

Competing Interests: Conflict of interest: The authors declare no competing interests.

Background: Liver fibrosis is a dynamic process marked by the accumulation of extracellular matrix due to hepatic stellate cells (HSCs) activation. Ginsenoside compound K (CK), a rare derivative of its parent ginsenosides, is known to significantly ameliorate metabolic disorders., Purpose: The aim of this study was to elucidate the protective effects of CK against liver fibrosis with a focus on metabolic regulation., Methods: We established liver fibrosis models in mice using carbon tetrachloride (CCl 4 ) challenge, bile duct ligation, or a methionine-choline deficient diet, with continuous oral administration of CK at specified doses and intervals. Simultaneously, we examined the impact of CK on metabolic regulation in cultured HSCs and investigated the associated mechanisms., Results: CK was found to alleviate liver injury and curb fibrotic responses in mouse models, as well as decrease elevated levels of liver enzyme. Metabolomic analysis in vitro highlighted the crucial roles of pyruvate and glutamine metabolism in metabolic remodeling. Immunohistochemical staining indicated significantly elevated expressions of lactate dehydrogenase A (LDHA) (p = 0.014) and glutaminase 1 (GLS1) (p = 0.024) in liver cirrhosis patients. Comparable alterations were noted in the liver of model mice and in cultured HSCs. Molecular docking and bio-layer interferometry demonstrated that CK interacts with and inhibits the activities of LDHA and GLS1. As expected, CK attenuated glycolysis and glutaminolysis, reducing HSC growth dependently on lactate and α-ketoglutarate (α-KG). Upon HSC activation, metabolism is reprogrammed with Myc as a key regulator, transcriptionally controlling LDHA, GLS1, and glutamine transporters SLC1A5 and SLC38A5. CK inhibited Myc induction, integrating glycolysis and glutaminolysis regulation to counteract the fibrotic response., Conclusion: CK inhibited LDHA and GLS1 activities, thereby inhibiting hepatic fibrosis. These findings offer new insights into the role of ginsenosides in liver protection, especially regarding metabolic disorders., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

Aggression and mating of male mice are strongly associated with Esr1-expressing neurons in the bed nucleus of the stria terminalis (BNSTpr) and hypothalamus in the vomeronasal pathway. By projecting to the downstream hypothalamus, the upstream BNSTpr Esr1 gates mating and aggression of male mice and maternal behavior of female mice. The medial preoptic area (MPOA) and ventrolateral subdivision of the ventromedial hypothalamus (VMHvl) are two subdivisions of the hypothalamus downstream. In addition to receiving projections from upstream BNSTpr, there is also a mutual projection between MPOA and VMHvl. In the process of transforming sex information into mating and aggression, Esr1-expressing neurons in BNSTpr, MPOA, and VMHvl act as messengers of information, finally producing inhibitory or excitatory projection. These projections are different in direction, but they all work together to control the behavior selection that is most conducive to defense and reproduction when male mice encounter female or male mice. Here, we summarized the property and the function of connections between these Esr1-expressing neurons in BNSTpr, MPOA, and VMHvl that encode mating and aggression and highlight the importance and benefits of inhibitory projection of Esr1-expressing cells in mating and aggression., Competing Interests: The authors declare no competing financial interests., (Copyright © 2024 Wang et al.)

A transdermal drug delivery cream, which is non-invasive and painless, containing a liposome-encapsulated Ru(II) complex (LipoRu) is created for the treatment of skin cancer. This formulation capitalizes on the synergistic antitumor effects of two-photon excited photodynamic therapy (PDT), photothermal therapy (PTT), and chemotherapy. LipoRu exhibits effective tumor accumulation, efficient cellular uptake, pH-sensitive and infrared-accelerated release, and dual localization to the nucleus and mitochondria. The released Ru(II) complexes within cells exert multiple antitumor mechanisms, such as DNA topoisomerase and RNA polymerase inhibition, Type I and II PDT, PTT, DNA photodamage, and apoptosis and ferroptosis induction. The biodistribution and therapeutic efficacy of LipoRu in vivo are systematically compared via three distinct administration routes: intratumoral injection, intravenous injection, and transdermal delivery through topical cream application. The positive therapeutic effects of the LipoRu cream fabricated here in subcutaneous tumor-bearing mice offer optimistic potential for the painless and non-invasive treatment of both early-stage and advanced skin cancers, as well as superficially located solid tumors., (© 2024 Wiley‐VCH GmbH.)

Six polypyridyl Ru(II) complexes were designed for single-molecule photodynamic and sonodynamic therapy (PDT/SDT) synergistic multimodal anticancer toward cisplatin-resistant NSCLC. They demonstrated lowest 3ES with distinct intraligand transition nature, which is beneficial for singlet oxygen generation. Remarkable quantum yields of both singlet oxygen and superoxide anion under either 808 nm laser irradiation or ultrasonic treatment and could induce apoptosis and ferroptosis of A549R cells. Cytotoxicity experiments clearly demonstrated a synergistic effect between PDT and SDT. The relationship between the structures of these complexes and their cellular biological mechanisms has been explored in detail. Using a single-molecule sensitizer to achieve synergistic PDT/SDT may provide valuable insights for the treatment of drug-resistant tumors that located deeply and in hypoxic microenvironment., (© 2024 Wiley-VCH GmbH.)

With the intention of advancing our research on diverse C-20 derivatives of camptothecin (CPT), 38 CPT derivatives bearing sulphonamide and sulfonylurea chemical scaffolds and different substituent groups have been designed, synthesised and evaluated in vitro for cytotoxicity against four tumour cell lines, A-549 (lung carcinoma), KB (nasopharyngeal carcinoma), MDA-MB-231 (triple-negative breast cancer) and KBvin (an MDR KB subiline). As a result, all the synthesised compounds showed promising in vitro cytotoxic activity against the four cancer cell lines tested, and were more potent than irinotecan. Importantly, compounds 12b , 12f , 12j and 13 l possessed better antiproliferative activity against all tested tumour cell lines with IC 50 values of 0.0118 - 0.5478 μM, and resulted approximately 3 to 4 times more cytotoxic than topotecan against multidrug-resistant KBvin subline. Convincing evidences are achieved that incorporation of sulphonamide and sulfonylurea motifs into position-20 of camptothecin confers markedly enhanced cytotoxic activity against cancer cell lines.

Introduction: Elevated glucagon levels are a characteristic feature of type 2 diabetes. This abnormal increase in glucagon can lead to an accelerated rate of gluconeogenesis. Glucagon also stimulates hepatic metabolism of amino acids, particularly promoting the formation of urea. The specific role of carbamoyl phosphate synthetase 1 (CPS1), a rate-limiting enzyme in the urea cycle, in the development versus the persistence of glucagon-induced hyperglycemia has not been previously established. Methods: The study employed both in vivo and in vitro approaches to assess the impact of CPS1 modulation on glucagon response. CPS1 was knockdown or overexpression to evaluate its influence on hepatic gluconeogenesis. In addition, an in-silico strategy was employed to identify a potential CPS1 inhibitor. Results: Knockdown of CPS1 significantly reduced the glucagon response both in vivo and in vitro . Conversely, overexpression of CPS1 resulted in an overactive hepatic gluconeogenic response. Mechanistically, CPS1 induced the release of calcium ions from the endoplasmic reticulum, which in turn triggered the phosphorylation of CaMKII. The activation of CaMKII then facilitated the dephosphorylation and nuclear translocation of FOXO1, culminating in the enhancement of hepatic gluconeogenesis. Furthermore, cynarin, a natural CPS1 inhibitor derived from the artichoke plant, had the capacity to attenuate the hepatic glucagon response in a CPS1-dependent manner. Discussion: CPS1 played a pivotal role in mediating glucagon-induced hepatic gluconeogenesis. The discovery of cynarin as a natural inhibitor of CPS1 suggested its potential as a therapeutic agent for diabetes treatment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Sun, Wu, Wei, Zhu, Wu, Zhou, Qi and Liu.)

Competing Interests: Conflicts of Interest: Yu P, None; Hu BY, None; He Y, None; Jing L, None; Fan HY, None; Shu J, None; Zeng LZ, None.

A planar conjugated ligand functionalized with bithiophene and its Ru(II), Os(II), and Ir(III) complexes have been constructed as single-molecule platform for synergistic photodynamic, photothermal, and chemotherapy. The complexes have significant two-photon absorption at 808 nm and remarkable singlet oxygen and superoxide anion production in aqueous solution and cells when exposed to 808 nm infrared irradiation. The most potent Ru(II) complex Ru7 enters tumor cells via the rare macropinocytosis, locates in both nuclei and mitochondria, and regulates DNA-related chemotherapeutic mechanisms intranuclearly including DNA topoisomerase and RNA polymerase inhibition and their synergistic effects with photoactivated apoptosis, ferroptosis and DNA cleavage. Ru7 exhibits high efficacy in vivo for malignant melanoma and cisplatin-resistant non-small cell lung cancer tumors, with a 100 % survival rate of mice, low toxicity to normal cells and low residual rate. Such an infrared two-photon activatable metal complex may contribute to a new generation of single-molecule-based integrated diagnosis and treatment platform to address drug resistance in clinical practice and phototherapy for large, deeply located solid tumors., (© 2024 Wiley-VCH GmbH.)

Background: The Bostrichidae is a small family of Coleoptera, with up to 600 described species all over the world. Almost 90 species of the family have been recorded in China at present and several new species of powder-post beetles have been described in recent years. Since the 1940s, the family Bostrichidae has become a neglected group in the taxonomy research of the Chinese mainland compared with its extensive territorial and super complex ecological diversity. Thus, there is need for more field specimen collection and in-depth taxonomic study., New Information: In this study, two powder-post beetles species Trogoxylonspinifrons (Lesne, 1910) and Mintheabivestita Lesne, 1937, are recorded for the first time from China. New provincial distribution records of another 18 Bostrichidae also listed., (Yi-Feng Zhang, Ying Wang, Wei Lin, Ling-Zeng Meng.)

Glaucoma is a common and complex neurodegenerative disease characterized by progressive loss of retinal ganglion cells (RGCs) and axons. Currently, there is no effective method to address the cause of RGCs degeneration. However, studies on neuroprotective strategies for optic neuropathy have increased in recent years. Cell replacement and neuroprotection are major strategies for treating glaucoma and optic neuropathy. Regenerative medicine research into the repair of optic nerve damage using stem cells has received considerable attention. Stem cells possess the potential for multidirectional differentiation abilities and are capable of producing RGC-friendly microenvironments through paracrine effects. This article reviews a thorough researches of recent advances and approaches in stem cell repair of optic nerve injury, raising the controversies and unresolved issues surrounding the future of stem cells., Competing Interests: Conflicts of Interest: Hu BY, None; Xin M, None; Chen M, None; Yu P, None; Zeng LZ, None., (International Journal of Ophthalmology Press.)

Background: Tongue diagnosis is a crucial traditional Chinese medicine (TCM) inspection method for TCM syndrome differentiation and treatment., Objective: The primary research focus was on tongue image characteristic parameters of patients with non-small cell lung cancer (NSCLC). Analysis of the tongue image parameters of various pathological stages of NSCLC provides technical support for establishing an integrated Chinese and Western auxiliary diagnosis and efficacy evaluation medicine system for lung cancer that integrates tongue image features., Methods: Tongue image characteristics of 309 patients with NSCLC and 206 controls were collected and analyzed clinically. The T-test or rank sum test and logistic regression analysis were applied to analyze the characteristics of tongue image indicators of different pathological stages of NSCLC., Results: There were differences in tongue image characteristics in the NSCLC group compared to the control group. The tongue quality and brightness of the tongue coating in the NSCLC group increased, the red component was reduced, the tongue coating thickened, and the yellow component increased compared to the healthy control group. A comparison of tongue image indexes of NSCLC in different pathological stages showed that stage IV had lower TB-b and higher TB-a than stage I. In addition, stage IV had lower TB-b than stage II + III, showing an increase in the blue and red components of the tongue in stage IV and the appearance of cyanotic tongue features., Conclusion: The tongue image characteristics of NSCLC patients differed from those of the control group. Tongue imaging indicators can reflect the characteristics of tongue images of patients with NSCLC. The tongue image characteristics of patients with stage IV lung cancer are bluish and purple compared with those with stage I, II, and III. It is suggested that the tongue's image characteristics can be used as a reference for the pathological classification of NSCLC and judgment of the disease process.

Background: Atherosclerotic renal artery stenosis (ARAS) is a common disease in the elderly population., Objective: The aim was to develop a contrast-enhanced ultrasound (CEUS)-based model for predicting post-angioplasty improvement in hypertension in patients with severe ARAS., Methods: Thirty-five patients with severe ARAS (⩾ 70%) were included in this study, and 42 renal arteries received percutaneous transluminal renal arterial stenting. An optimal integral formula was developed from pre-interventional color-coded duplex sonography (CCDS) and CEUS parameters using least absolute shrinkage and selection operator (LASSO) regression and receiver operating characteristic (ROC) curve analysis. A model for predicting short-term hypertension improvement was established using the integral formula and clinical risk factors. Bootstrapping was used for internal validation., Results: Two integral formulas, LASSO.CCDS and LASSO.CEUS, were established. ROC curves of the two integral formulas showed that LASSO.CEUS was the better formula for predicting hypertension improvement (AUC 0.816, specificity 78.6%). Univariate and multivariate regression analyses showed that duration of hypertension (OR 0.841, P= 0.027), diabetes (OR = 0.019, P= 0.010), and LASSO.CEUS (OR 7.641, P= 0.052) were predictors of short-term hypertension improvement after interventional therapy. Using LASSO.CEUS combined with clinical risk factors, the following prediction model was established: logit (short-term improvement in hypertension) = 1.879-0.173 × hypertension duration - 3.961 × diabetes + 2.034 × LASSO.CEUS (AUC 0.939)., Conclusions: The model established using CEUS parameters and clinical risk factors could predict hypertension improvement after interventional therapy, but further research and verification are needed.

Aim: To evaluate the clinical significance of checking episcleral venous fluid wave (EVFW) during gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open angle glaucoma (OAG)., Methods: This retrospective case series study comprised 30 patients (45 eyes) with OAG underwent GATT. The location and extent of EVFW were examined and graded after intraoperative compression flushing of the anterior chamber angle during the operation. Patients were followed up for 1y. A complete success for surgery is defined as a postoperative intraocular pressure (IOP) <18 mm Hg without any anti-glaucoma medication. IOP<18 mm Hg with less than two anti-glaucoma medications is defined as qualified success, while the control of IOP requiring three anti-glaucoma medications is considered as unsuccess., Results: The mean IOP was 35.38±7.16 mm Hg before surgery and 15.52±4.22 mm Hg 1y after surgery ( P <0.01). The average number of anti-glaucoma medication was 2.8±1.2 (2-4) preoperation and 0.6±1.3 (0-3) 1y postoperation ( P <0.01). The success rate of the operation was 93.33%. Complete success rate was 66.67%, qualified success rate was 26.67%, and 6.66% of unsuccessful cases required reoperation. EVFW of all cases was grade 2-4, and the percentages of grade 2, 3 and 4 were 33.33%, 40.0% and 26.67%, respectively. The distribution and percentage of EVFW were inferior (36%), nasal (28%), superior (20%), and temporal (16%). The EVFW grade of complete success patients was 3.4±0.6 (3-4), and that of qualified success patients was 2.6±1.0 (2-4). The larger the range of EVFW, the lower the IOP, and the better the IOP reduction effect., Conclusion: During GATT surgery, pressurized irrigation of anterior chamber to check EVFW can reduce the outflow resistance of aqueous humor and increase the effect of postoperative IOP. The range of EVFW is negatively correlated with postoperative IOP. Therefore, EVFW may be a valuable prognostic indicator for the success of GATT surgery., (International Journal of Ophthalmology Press.)

A series of cyclometalated Ir(III) complexes with morpholine and piperazine groups are designed as dual photosensitizers and photothermal agents for more efficient antitumor phototherapy via infrared low-power laser. Their ground and excited state properties, as well as the structural effect on their photophysical and biological properties, are investigated by spectroscopic, electrochemical, and quantum chemical theoretical calculations. They target mitochondria in human melanoma tumor cells and trigger apoptosis related to mitochondrial dysfunction upon irradiation. The Ir(III) complexes, particularly Ir6, demonstrate high phototherapy indexes to melanoma tumor cells and a manifest photothermal effect. Ir6, with minimal hepato-/nephrotoxicity in vitro, significantly inhibits the growth of melanoma tumors in vivo under 808 nm laser irradiation by dual photodynamic therapy and photothermal therapy and can be efficiently eliminated from the body. These results may contribute to the development of highly efficient phototherapeutic drugs for large, deeply buried solid tumors., (© 2023 Wiley-VCH GmbH.)

Immanus Hulcr & Cognato, 2013 is reported from China for the first time, with the description and illustration of a new species, Immanus songi sp. nov., based on an adult female collected with a flight intercept trap from Yunnan province, China. A key to all known species of Immanus is given.

Cyclometalated iridium(III) complexes are of significant importance in the field of antitumor photodynamic therapy (PDT), whether they exist as single molecules or are incorporated into nanomaterials. Nevertheless, a comprehensive examination of the relationship between their molecular structure and PDT effectiveness remains awaited. The influencing factors of two-photon excited PDT can be anticipated to be further multiplied, particularly in relation to intricate nonlinear optical properties. At present, a comprehensive body of research on this topic is lacking, and few discernible patterns have been identified. In this study, through systematic structure regulation, the nitro-substituted styryl group and 1-phenylisoquinoline ligand containing YQ2 was found to be the most potent infrared two-photon excitable photosensitizer in a 4 × 3 combination library of cyclometalated Ir(III) complexes. YQ2 could enter cells via an energy-dependent and caveolae-mediated pathway, bind specifically to mitochondria, produce 1 O 2 in response to 808 nm LPL irradiation, activate caspases, and induce apoptosis. In vitro, YQ2 displayed a remarkable phototherapy index for both malignant melanoma (>885) and non-small-cell lung cancer (>1234) based on these functions and was minimally deleterious to human normal liver and kidney cells. In in vivo antitumor phototherapy, YQ2 inhibited tumor growth by an impressive 85% and could be eliminated from the bodies of mice with a half-life as short as 43 h. This study has the potential to contribute significantly to the development of phototherapeutic drugs that are extremely effective in treating large, profoundly located solid tumors as well as the understanding of the structure-activity relationship of Ir(III)-based PSs in PDT.

Primary liver cancer is one of the most common malignant cancers of the digestive system that lacks effective chemotherapeutic drugs in clinical settings. Camptothecin (CPT) and its derivatives have been approved for cancer treatment; however, their application is limited by their systemic toxicity. For lead optimization in new drug discovery stages, fluorination is an effective and robust approach to increase the bioavailability and optimize the pharmacokinetics of candidate compounds, thereby improving their efficacy. To obtain new and highly active CPT derivatives, we designed, synthesized, and evaluated two new fluorinated CPT derivatives, 9-fluorocamptothecin (A1) and 7-ethyl-9-fluorocamptothecin (A2), in this study. In vitro, A1 and A2 exhibited more robust anti-tumor activity than topotecan (TPT) in various cancer cells, particularly hepatocellular carcinoma (HCC) cells. In vivo, A1 and A2 exhibited greater anti-tumor activity than TPT in both AKT/Met induced primary HCC mouse models and implanted HepG2 cell xenografts. Acute toxicity tests revealed that A1 and A2 were not lethal and did not cause significant body weight loss at high doses. Moreover, A1 and A2 exhibited no significant toxicity in the mouse liver, heart, lung, spleen, kidney, and hematopoietic systems at therapeutic doses. Mechanistically, A1 and A2 blocked HCC cell proliferation by inhibiting the enzymatic activity of Topo I, subsequently inducing DNA damage, cell cycle arrest, and apoptosis. In summary, our results indicate that fluorination improves the anti-tumor activity of CPT while decreasing its toxicity and highlight the application potential of fluorination products A1 and A2 in clinical settings., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: This study sought to investigate the applicability of different ultrasound (US) thyroid risk stratification systems in diagnosing medullary thyroid carcinoma (MTC) and determining the need for biopsy., Methods: In total, 34 MTC nodules, 54 papillary thyroid carcinoma (PTC) nodules, and 62 benign thyroid nodules were examined in this study. All the diagnoses were histopathologically confirmed postoperatively. All the thyroid nodule sonographic features were recorded and categorized by 2 independent reviewers according to the Thyroid Imaging Reporting and Data System (TIRADS) of the American College of Radiology (ACR), the American Thyroid Association (ATA) guidelines, the European Thyroid Association (EU) TIRADS, the Kwak-TIRADS, and the Chinese TIRADS (C-TIRADS). The sonographic differences and risk stratifications of the MTCs, PTCs, and benign thyroid nodules were analyzed. The diagnostic performance and recommended biopsy rates for each classification system were evaluated., Results: The risk stratifications of MTCs were all higher than the benign thyroid nodules (P<0.01) and lower than PTCs (P<0.01) with each classification system. Hypoechogenicity and malignant marginal features were independent risk factors for identifying malignant thyroid nodules, and the area under the receiver operating characteristic curve (AUC) for identifying MTCs was lower than that for identifying PTCs (0.873 vs . 0.954, respectively). The AUCs, sensitivity, specificity, positive predictive values, negative predictive values, and accuracy values of the 5 systems for MTC were all lower than those for PTC. The best cut-off values for diagnosing MTC were TIRADS (TR) 4 in the ACR-TIRADS, intermediate suspicion in the ATA guidelines, TR 4 in EU-TIRADS, and TR 4b in both the Kwak-TIRADS and the C-TIRADS. The Kwak-TIRADS had the highest recommended biopsy rate for MTCs (97.1%), followed by the ATA guidelines, the EU-TIRADS (88.2%), the C-TIRADS (85.3%), and the ACR-TIRADS (79.4%)., Conclusions: The US-based thyroid malignancy risk stratification systems analyzed in this study were able to satisfactorily identify MTC and recommend biopsy, but the diagnostic performance of these systems for MTC was not as good as that for PTC., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://qims.amegroups.com/article/view/10.21037/qims-22-968/coif). The authors have no conflicts of interest to declare., (2023 Quantitative Imaging in Medicine and Surgery. All rights reserved.)

Aims: In this study, we synthesized a 10-fluorine-substitution derivative of CPT (Camptothecin) YCJ100 and evaluated its antitumor activity and systemic toxicity., Materials and Methods: Determination of in vitro antitumor activity and mechanism of YCJ100 by the MTT assay, Molecular docking, EdU staining, Cell cycle and apoptosis determination, Western blot analysis and Topoisomerase I activity assay. The antitumor effects of YCJ100 were evaluated in primary HCC (hepatocellular carcinoma), ICC (intrahepatic cholangiocarcinoma) mouse models, and pancreatic cancer xenograft models., Key Findings: YCJ100 showed superior cytotoxic activity compared to Topotecan in SW480, SW1990, Hep3B, HepG2, A549, A2780, HeLa, and QBC cells. YCJ100 blocked the cell cycle in the G2/M phase, inhibited cell proliferation and induced apoptosis in HepG2 and SW1990 cells. Mechanistically, YCJ100 inhibited topoisomerase I activity in both a cell-free system and a cellular system, similar to the mechanism of Topotecan. YCJ100 showed significant antitumor activity and was more potent than Topotecan in primary HCC and ICC mouse models, as well as a xenograft mouse model. Additionally, YCJ100 showed only minor toxicity to the mouse hematopoietic system, liver, and kidney. These findings indicate that YCJ100 has high antitumor activity and low systemic toxicity., Significance: Our findings demonstrate that YCJ100, as a Topoisomerase I inhibitor, has in vitro and in vitro antitumor activity. This study provides a new lead compound worthy of further preclinical evaluation and potential clinical development., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier Inc.)

Introduction: Chitosan is the product of the natural polysaccharide chitin removing part of the acetyl group, and exhibits various physiological and bioactive functions. Selenium modification has been proved to further enhance the chitosan bioactivities, and has been a hot topic recently., Methods: The present study aimed to investigate the potential inhibitory mechanism of selenium-modified chitosan (SMC) on HepG2 cells through MTT assays, morphological observation, annexin V-FITC/PI double staining, mitochondrial membrane potential determination, cell-cycle detection, Western blotting, and two-dimensional gel electrophoresis (2-DE)., Results: The results indicated that SMC can induce HepG2 cell apoptosis with the cell cycle arrested in the S and G 2 /M phases and gradual disruption of mitochondrial membrane potential, reduce the expression of Bcl2, and improve the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3. Also, 2-DE results showed that tubulin α 1 B chain, myosin regulatory light chain 12A, calmodulin, UPF0568 protein chromosome 14 open reading frame 166, and the cytochrome C oxidase subunit 5B of HepG2 cells were downregulated in HepG2 cells after SMC treatment., Discussion: These data suggested that HepG2 cells induced apoptosis after SMC treatment via blocking the cell cycle in the S and G 2 /M phases, which might be mediated through the mitochondrial apoptotic pathway. These results could be of benefit to future practical applications of SMC in the food and drug fields., Competing Interests: The authors declare that they have no conflicts of interest in this work., (© 2022 Sun et al.)

Background: To observe alterations of fundus microcirculation and retinal thickness in adolescent myopic patients with astigmatism after toric and spherical orthokeratology using optical coherence tomography angiography (OCTA), to explore the effects of orthokeratology on the retinal thickness and choroidal blood flow., Methods: A total of 48 patients were enrolled and divided into two group (toric orthokeratology (T) group and spherical orthokeratology (S) group) according to the type of lens design. OCTA was used to measure the superficial and deep retinal vessel densities at the macular region, radial peripapillary capillary (RPC) density, foveal avascular zone (FAZ) area, and choriocapillaris (ChC) perfusion area before and after orthokeratology for 3 months. The data were statistically analyzed by SPSS 19.0 software., Results: Compared with before orthokeratology, the superficial vessel density in the fovea and parafovea in the T group significantly increased, and the deep vessel density in the whole area and fovea were significantly elevated after 3 months (P < 0.05). The superficial vessel density was significantly higher only in the parafovea in the S group after 3 months than that before orthokeratology (P < 0.05), deep vessel density in the whole area and parafovea after 3 months was significantly higher than that before orthokeratology (P < 0.05). RPC density in the two groups increased after 3 months of orthokeratology in the whole area and inside the disc area (P < 0.05). Three months after toric orthokeratology, FAZ area in the T group was significantly reduced by 0.05 (- 0.41 to + 0.08) mm 2 , while ChC perfusion area was enlarged by 0.06 ± 0.12 mm 2 . FAZ area in the S group significantly decreased by 0.01 (- 0.19 to + 0.01) mm 2 , whereas ChC perfusion area increased by 0.06 (- 0.07 to + 0.50) mm 2 . Retinal thickness in the two groups increased after 3 months of orthokeratology in the whole area and parafoveal area (P < 0.05)., Conclusion: Orthokeratology improved retinal blood flow in macular area and RPC while controlling myopia. The changes in FAZ and ChC perfusion areas did not significantly differ between toric and spherical orthokeratology., (© 2022. The Author(s).)

The ethanol precipitation method has been widely-used for Dendrobium officinale polysaccharides preparation. However, the alcohol-soluble fractions have always been ignored, which causes significant wastes of resources and energies. In this study, the extraction, physicochemical properties, and immune regulation activity of an edible D. officinale polysaccharide (DOPs) isolated from the supernatant after 75% ethanol precipitation were systematically investigated. The structural characteristics determination results showed that DOPs was mainly composed of glucose and mannose at a molar ratio of 1.00:5.78 with an average molecular weight of 4.56 × 10 3 Da, which was made up of α-(1,3)-Glc p as the main skeleton, and the α-(1,4)-Glc p and β-(1,4)-Man p as the branches. Subsequently, the cyclophosphamide (CTX)-induced immunosuppressive mice model was established, and the results demonstrated that DOPs could dose-dependently protect the immune organs against CTX damage, improve the immune cells activities, and promote the immune-related cytokines (IL-2, IFN-γ and TNF-α) secretions. Furthermore, DOPs treatment also effectively enhanced the antioxidant enzymes levels (SOD, GSH-Px) in sera and livers, therefore weakening the oxidative damage of CTX-treated mice. Considering these above data, DOPs presented great potential to be explored as a natural antioxidant and supplement for functional foods.

NLRP3 inflammasome activation plays a key role in a variety of inflammatory diseases as IBD. Here a series of pterostilbene derivatives were designed and synthesized based on previous SAR, leading to discovery of new effective NLRP3 inflammasome inhibitors with metabolic stability. Among them, the most effective compound 27 showed high inhibitory efficacy (against IL-1 β: IC 50  = 1.23 μM) and almost no toxicity (against L02: IC 50  > 100 μM). Further mechanism studies have shown that compound 27 directly targets the NLRP3 and affects the assembly of inflammasomes to inhibit the activation of NLRP3 inflammasomes. More importantly, in vitro experiments show that compound 27 has a significant therapeutic effect on DSS-induced colitis in mice with good metabolic stability to liver microsomes (t 1/2  = 138.6 min). This research encourages the further development of more effective NLRP3 inflammasome inhibitors based on this chemical scaffold., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Indoleamine 2,3-dioxygenase 1 (IDO1) plays a predominant role in cancer immunotherapy which catalyzes the initial and rate limiting steps of the kynurenine pathway as a key enzyme. To explore novel IDO1 inhibitors, five derivatives of erlotinib-linked 1,2,3-triazole compounds were designed by using a structure-based drug design strategy. Drug-target interactions (DTI) were predicted by DeePurpose, an easy-to-use deep learning library that contains more than 50 algorithms. The DTI prediction results suggested that the designed molecules have potential inhibitory activities for IDO1. Chemical syntheses and bioassays showed that the compounds exhibited remarkable inhibitory activities against IDO1, among them, compound e was the most potent with an IC 50 value of 0.32 ± 0.07 μM in the Hela cell assay. The docking model and ADME analysis exhibited that the effective interactions of these compounds with heme iron and better drug-likeness ensured the IDO1 inhibitory activities. The studies suggested that compound e was a novel and interesting IDO1 inhibitor for further development., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Xu, Gong, Zhu, Yao, Peng, Sun, Yang and Mao.)

Background: Separation of biotic and abiotic impacts on species diversity distribution patterns across a significant climatic gradient is a challenge in the study of diversity maintenance mechanisms. The basic task is to reconcile scale-dependent effects of abiotic and biotic processes on species distribution models. Here, we used a hierarchical modeling method to detect the host specificities of bark beetles (Scolytinae and Platypodinae) with their dependent tree communities across a steep climatic gradient, which was embedded within a relatively homogenous spatial niche., Results: Species turnover of both trees and bark beetles have an opposite pattern along the climatic proxy (represented by the elevation gradients) at the regional scale, but not at local spatial scales. This pattern confirmed the hypothesis wherein emphasis was on influences of macro-climate on local biotic interactions between trees and hosted bark beetle communities, whereas local biotic relations, represented by host specificity dependence, were regionally conserved., Conclusions: At a confined spatial scale, cross-taxa comparisons of β-diversity highlighted the importance of simultaneous impacts from both extrinsic factors related to geography and environment, and intrinsic factors related to organism characteristics. The effects of tree abundance and phylogeny diversity on bark beetle diversity were, to a large extent, indirect, operating via changes in bark beetle abundance through spatial and temporal dynamics of resources distribution. Tree host dependence, which was considered and represented by host specificities, plays a minor role on the hosted beetle community in this concealed wood decomposing interacting system., (© 2022. The Author(s).)

The powder post beetles (Coleoptera: Bostrichidae) (except Lyctinae) of Yunnan Province in Southwest China are reviewed for the first time. Keys to twenty-six genera and fifty-two species from the Yunnan region are provided. One new genus and seven new species are described: Dinoderus (Dinoderastes) hongheensis sp. nov., Dinoderus (Dinoderastes) nanxiheensis sp. nov., Gracilenta yingjiangensis gen. nov., sp. nov., Calonistes vittatus sp. nov., Calophagus colombiana sp. nov., Xylodrypta guochuanii sp. nov. and Xylodrypta zhenghei sp. nov.. Fourteen species are recorded in China for the first time. The bostrichid fauna of Yunnan is compared with those of the neighbouring bio-geographically related Southeast Asian and Himalayan regions. The fauna has a close affinity with that of tropical Southeast Asia and a much weaker relationship with the Palearctic region. The differences with the Himalayas may reflect the separate evolutionary and complex geological history of the two areas.

Studies have shown that the abnormal activation of the NLRP3 inflammasome is involved in a variety of inflammatory-based diseases. In this study, a high content screening model targeting the activation of inflammasome was first established and pterostilbene was discovered as the active scaffold. Based on this finding, total of 50 pterostilbene derivatives were then designed and synthesized. Among them, compound 47 was found to be the best one for inhibiting cell pyroptosis [inhibitory rate (IR) = 73.09% at 10 μM], showing low toxicity and high efficiency [against interleukin-1β (IL-1β): half-maximal inhibitory concentration (IC 50 ) = 0.56 μM]. Further studies showed that compound 47 affected the assembly of the NLRP3 inflammasomes by targeting NLRP3. The in vivo biological activity showed that this compound significantly alleviated dextran sodium sulfate (DSS)-induced colitis in mice. In general, our study provided a novel lead compound directly targeting the NLRP3 protein, which is worthy of further research and structural optimization.

Phycosphere hosts the boundary of unique holobionts harboring dynamic algae-bacteria interactions. During our investigating the microbial consortia composition of phycosphere microbiota (PM) derived from diverse harmful algal blooms (HAB) dinoflagellates, a novel rod-shaped, motile and faint yellow-pigmented bacterium, designated as strain LZ-6  T , was isolated from HAB Alexandrium catenella LZT09 which produces high levels paralytic shellfish poisoning toxins. Phylogenetic analysis based on 16S rRNA gene and two housekeeping genes, rpoA and pheS sequences showed that the novel isolate shared the highest gene similarity with Marinobacter shengliensis CGMCC 1.12758  T (99.6%) with the similarity values of 99.6%, 99.9% and 98.5%, respectively. Further phylogenomic calculations of average nucleotide identity (ANI), average amino acid identity (AAI) and digital DNA-DNA hybridization (dDDH) values between strains LZ-6  T and the type strain of M. shengliensis were 95.9%, 96.4% and 68.5%, respectively. However, combined phenotypic and chemotaxonomic characterizations revealed that the new isolate was obviously different from the type strain of M. shengliensis. The obtained taxonomic evidences supported that strain LZ-6  T represents a novel subspecies of M. shengliensis, for which the name is proposed, Marinobacter shengliensis subsp. alexandrii subsp. nov. with the type strain LZ-6  T (= CCTCC AB 2018388T T  = KCTC 72197  T ). This proposal automatically creates Marinobacter shengliensis subsp. shengliensis for which the type strain is SL013A34A2 T (= LMG 27740  T  = CGMCC 1.12758  T ).

In order to discover and develop drug-like anti-inflammatory agents against arthritis, based on "Hit" we found earlier and to overcome drawbacks of toxicity, twelve series of total 89 novel pyrimidine, pyrazolo[4,3-d]pyrimidine and thieno[3,2-d]pyrimidine derivatives were designed, synthesized and screened for their anti-inflammatory activity against NO and toxicity for normal liver cells (LO2). Relationships of balance toxicity and activity have been summarized through multi-steps, and title compounds 22o, 22l were found to show lower toxicity (against LO2: IC 50  = 2934, 2301 μM, respectively) and potent effect against NO release (IR = 98.3, 97.67%, at 10 μM, respectively). Furthermore, compound 22o showed potent iNOS inhibitory activity with value of IC 50 is 0.96 μM and could interfere stability and formation of the active dimeric iNOS. It's anti-inflammatory activity in vivo was assessed by AIA rat model. Furthermore, the results of metabolic stability, CYP, PK study in vivo, acute toxicity study and subacute toxicity assessment indicated this compound had good drug-like properties for treatment., Competing Interests: Declaration of competing interest All authors have contributed to the work, have read the manuscript and have agreed to be listed as authors. The submitted manuscript has not been published elsewhere and nor is it currently under review by another publication. No potential conflict of interest relevant to this article.., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Longhorn beetles are extremely rich wood-boring insects possessing larvae that feed on the xylem of trees and/or lianas, which have detrimental effects on plants; in turn, the hosting plants may play a fundamental role in shaping the longhorn beetle community assemblage. However, factors determining the community assemblage of wood-boring longhorn beetles, particularly along the multiple spatial scales is still in need of further exploration. In this study, we designed an experiment across several spatial scales (from local to macro scales) from tropical to temperate climate gradients in Yunnan province, southwest China to examine to what extend the attributes of host-specificity is shaping the community assemblage along different spatial scales. This study concludes that (1) the wood-boring longhorn beetles showed attributes of host-specificity to a certain degree at the community level, (2) biotic (host plant specificity) and abiotic (climatic gradients) factors jointly shaped community composition of this species along the multiple spatial scales, (3) biotic interactions have a prominent effect on the community composition of this species at local-scale while macroclimatic gradients impose the major control on it at macro-scale. Thus, this study highlights the significance of host specificity in affecting the wood-boring longhorn beetle community assemblage, particularly at local scales.

Background: High myopia (HM) is a risk factor for several pathological structural changes in retinal and choroidal thickness or vessel. To date, changes in retinal and choroidal microvasculature circulations in HM have yielded inconsistent results., Objectives: The objective of this article was to evaluate alterations in retinal and choroidal thickness, and capillary microvasculature using optical coherence tomography angiography (OCTA) in HM., Methods: PubMed, Embase, and the Cochrane Library databases were searched for relevant published studies. Primary outcomes were foveal avascular zone, vessel density, retinal nerve fiber layer (RNFL) thickness, foveal thickness, sub-foveal choroidal thickness, and chorio-capillary density. Alterations in outcomes were evaluated by standardized mean difference with a 95% confidence interval., Results: Eleven eligible articles were included for the meta-analysis. The whole superficial and deep vessel densities of macular and parapapillary superficial vessel density were lower in HM than in control eyes. The thickness of parafoveal RNFL, parapapillary RNFL, and sub-foveal choroid was significantly lower in HM eyes. Also, chorio-capillary density was shown to be lower in HM eyes., Conclusions: The retinal and choroidal vessel network change may be related to the axial elongation in the progression of myopia. Furthermore, OCTA is an effective and noninvasive technology for monitoring the progress of myopia eyes., (© 2021 The Author(s). Published by S. Karger AG, Basel.)

Phthalide is a promising chemical scaffold and has been proved to show potent anti-inflammatory efficacy. In this study, three series, total of 31 novel phthalide derivatives were designed and synthesized, their anti-inflammatory activities were screened in vitro and in vivo. The anti-inflammatory activity of all the compounds were screened on LPS induced NO production to evaluating their inhibitory effects. Structure-activity relationship has been concluded, and finally 3-((4-((4-fluorobenzyl)oxy)phenyl)(hydroxy)methyl)-5,7-dimethoxyisobenzofuran-1 (3H)-one (compound 9o) was found to be the active one with low toxicity, which showed 95.23% inhibitory rate at 10 μM with IC 50 value of 0.76 μM against LPS-induced NO over expression. Preliminary mechanism studies indicated that compound 9o activated Nrf2/HO-1 signaling pathway via accumulation ROS and blocks the NF-κB/MAPK signaling pathway. The in vivo anti-inflammatory activity shown that compound 9o had obvious therapeutic effect against the adjuvant-induced rat arthritis model., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Masson SAS. All rights reserved.)

Strains J15B81-2 T and J15B91 T were isolated from a sediment sample collected from the South China Sea. Cells of both strains were observed to be rod-shaped, non-gliding, Gram-stain-negative, yellow-pigmented, facultatively anaerobic, catalase-positive, oxidase-negative and showing optimum growth at 30 °C. Strains J15B81-2 T and J15B91 T could tolerate up to 9 and 10  % (w/v) NaCl concentration and grow at pH 6.5-9.5 and 6.0-9.0, respectively. The strains shared 97.4 % 16S rRNA gene sequence similarity to each other but were identified as two distinct species based on 81.1-85.8 % ANIb and 31.5 % dDDH values calculated using whole genome sequences. Strains J15B81-2 T and J15B91 T shared highest 16S rRNA gene sequence similarity to Salinimicrobium xinjiangense CGMCC 1.12522 T (98.4 %) and Salinimicrobium sediminis CGMCC 1.12641 T (98.0 %), respectively. Among species with validly published names, S. sediminis CGMCC 1.12641 T shared close genetic relatedness with strains J15B81-2 T [85.1-85.3% average nucleotide identity based on blastBlast+ (ANIb) and 30.6 % digital DNA-DNA hybridization (dDDH)] and J15B91 T (76.6-79.1 % ANIb and 21.5 % dDDH). The major fatty acid of strains J15B81-2 T and J15B91 T were identified as iso-C 15 : 0 and iso-C 16 : 0 , respectively, and the major polar lipids of the two strains consisted of phosphatidylethanolamine, one unidentified phospholipid, one unidentified aminolipid and one unidentified lipid. The strains contained MK-6 as their predominant menaquinone. The genomic G+C contents of strains J15B81-2 T and J15B91 T were determined to be 41.7 and 41.8 mol %, respectively. Both strains are considered to represent two novel species of the genus Salinimicrobium and the names Salinimicrobium nanhaiense sp. nov. and Salinimicrobium oceani sp. nov. are proposed for strains J15B81-2 T (=KCTC 72867 T =MCCC 1H00410 T ) and J15B91 T (=KCTC 72869 T =MCCC 1H00411 T ), respectively.

There is a bidirectional relationship between inflammatory bowel disease (IBD) and depression/anxiety. Emerging evidences indicate that the liver may be involved in microbiota-gut-brain axis. This experiment focused on the role of melatonin in regulating the gut microbiota and explores its mechanism on dextran sulphate sodium- (DSS-) induced neuroinflammation and liver injury. Long-term DSS-treatment increased lipopolysaccharide (LPS), proinflammation cytokines IL-1 β and TNF- α , and gut leak in rats, breaking blood-brain barrier and overactivated astrocytes and microglia. Ultimately, the rats showed depression-like behavior, including reduction of sucrose preference and central time in open field test and elevation of immobility time in a forced swimming test. Oral administration with melatonin alleviated neuroinflammation and depression-like behaviors. However, melatonin supplementation did not decrease the level of LPS but increase short-chain fatty acid (SCFA) production to protect DSS-induced neuroinflammation. Additionally, western blotting analysis suggested that signaling pathways farnesoid X receptor-fibroblast growth factor 15 (FXR-FGF 15) in gut and apoptosis signal-regulating kinase 1 (ASK1) in the liver overactivated in DSS-treated rats, indicating liver metabolic disorder. Supplementation with melatonin markedly inhibited the activation of these two signaling pathways and its downstream p38. As for the gut microbiota, we found that immune response- and SCFA production-related microbiota, like Lactobacillus and Clostridium significantly increased, while bile salt hydrolase activity-related microbiota, like Streptococcus and Enterococcus , significantly decreased after melatonin supplementation. These altered microbiota were consistent with the alleviation of neuroinflammation and metabolic disorder. Taken together, our findings suggest melatonin contributes to reshape gut microbiota and improves inflammatory processes in the hippocampus (HPC) and metabolic disorders in the liver of DSS rats., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wei-jie Lv et al.)

Nanozymes have been widely applied in bio-assays in the field of biotechnology and biomedicines. However, the physicochemical basis of nanozyme catalytic activity remains elusive. To test whether nanozymes exhibit an inactivation effect similar to that of natural enzymes, we used guanidine chloride (GuHCl) to disturb the iron oxide nanozyme (IONzyme) and observed that GuHCl induced IONzyme aggregation and that the peroxidase-like activity of IONzyme significantly decreased in the presence of GuHCl. However, the aggregation appeared to be unrelated to the quick process of inactivation, as GuHCl acted as a reversible inhibitor of IONzyme instead of a solo denaturant. Inhibition kinetic analysis showed that GuHCl binds to IONzyme competitively with H 2 O 2 but non-competitively with tetramethylbenzidine. In addition, electron spin resonance spectroscopy showed that increasing GuHCl level of GuHCl induced a correlated pattern of changes in the activity and the state of the unpaired electrons of the IONzymes. This result indicates that GuHCl probably directly interacts with the iron atoms of IONzyme and affects the electron density of iron, which may then induce IONzyme inactivation. These findings not only contribute to understanding the essence of nanozyme catalytic activity but also suggest a practically feasible method to regulate the catalytic activity of IONzyme., (Copyright © 2020 Mo, Yu, Gao, Liu, Wei and He.)

Some important pro-inflammatory cytokines such as interleukin-6, tumor necrosis factor-α and nitric oxide are thought to play key roles in the destruction of cartilage and bone tissue in joints affected by rheumatoid arthritis. In the present study, a series of new myricetin-pentadienone hybrids were designed and synthesized. Majority of them effectively inhibited the expressions liposaccharide-induced secretion of IL-6, TNF-α and NO in RAW264.7. The most prominent compound 5o could significantly decrease production of above inflammatory factors with IC 50 values of 5.22 µM, 8.22 µM and 9.31 µM, respectively. Preliminary mechanism studies indicated that it could inhibit the expression of thioredoxin reductase, resulting in inhibiting of cell signaling pathway nuclear factor (N-κB) and mitogen-activated protein kinases. Significantly, compound 5o was found to effectively inhibit Freund's complete adjuvant induced rat adjuvant arthritis in vivo., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Delayed greening of young leaves is a ubiquitous and visually striking phenomenon in the tropics. Here, we investigated the potential ecological functions of red coloration patterns in young leaves. To detect any protective function of the red coloration on the young leaves, leaf damage by insect herbivores was recorded in the field. To determine capacity for chemical defense, the concentrations of tannins and anthocyanins were measured in both young and mature leaves. To test the hypothesis that anthocyanins function as photo-protective molecules, chlorophyll content, maximum photochemical efficiency of PSII ( F v / F m ), non-photochemical quenching ( NPQ ), and effective quantum yield of PSII ( Φ PSII ) were measured in the field. Phylogenetic relationships were analyzed to test the relationary significance of the occurrence of redness in young leaves. Compared to the coloration in non-red leaves, young red leaves had significant higher anthocyanins and tannins content and lower herbivore damages. Young, red leaves had the lowest F v / F m values, which were significantly lower than those of non-red leaves. NPQ values in young red leaves were comparable to those of other groups. Although young red leaves had high Φ PSII , these values were significantly lower than those of the other three groups. The results suggest that the red coloration of young leaves protects them from insect herbivory primary by chemical defense through high concentrations of tannins and anthocyanins. Additionally, low F v / F m values in young red leaves indicate that anthocyanins might not be functioning as light attenuators to compensate for insufficient photo-protection mediated by NPQ . And finally, red coloration in young leaves is predominantly a result of adaptation to heavy herbivory stress but without significant intrinsic phylogenetic relationship of plant species., (Copyright © 2020 Gong, Liu, Wang, Chen, Martin and Meng.)

Purpose: Studies have shown the association between tongue color and diseases. To help clinicians make more objective and accurate decisions quickly, we take unsupervised learning to deal with the basic clustering of tongue color in a 2D way., Methods: A total of 595 typical tongue images were analyzed. The 3D information extracted from the image was transformed into 2D information by principal component analysis (PCA). K-Means was applied for clustering into four diagnostic groups. The results were evaluated by clustering accuracy (CA), Jaccard similarity coefficient (JSC), and adjusted rand index (ARI)., Results: The new 2D information totally retained 89.63% original information in the L*a*b* color space. And our methods successfully classified tongue images into four clusters and the CA, ARI, and JSC were 89.04%, 0.721, and 0.890, respectively., Conclusions: The 2D information of tongue color can be used for clustering and to improve the visualization. K-Means combined with PCA could be used for tongue color classification and diagnosis. Methods in the paper might provide reference for the other research based on image diagnosis technology.

A minor alteration in structure of a previously reported synthetic K+ channel via replacing the electron-withdrawing group with an electron-donating group leads to enhancement in activity by 160% and in selectivity by >50%. As a result, the new K+ channel 10F5, despite having a simple structure, exhibits a high K+/Na+ selectivity of 14.0.

Epigallocatechin gallate (EGCG) is a natural phenolic compound found in many plants, especially in green tea, which is a popular and restorative beverage with many claimed health benefits such as antioxidant, anti-cancer, anti-microbial, anti-diabetic, and anti-obesity activities. Despite its great curative potential, the poor bioavailability of EGCG restricts its clinical applcation. However, nanoformulations of EGCG are emerging as new alternatives to traditional formulations. This review focuses on the nanochemopreventive applications of various EGCG nanoparticles such as lipid-based, polymer-based, carbohydrate-based, protein-based, and metal-based nanoparticles. EGCG hybridized with these nanocarriers is capable of achieving advanced functions such as targeted release, active targeting, and enhanced penetration, ultimately increasing the bioavailability of EGCG. In addition, this review also summarizes the challenges for the use of EGCG in therapeutic applications, and suggests future directions for progress.

Four series of total 35 new pyrazolo[4,3- d ]pyrimidine compounds were designed, synthesized and evaluated for their inhibitory activity against LPS-induced NO production in RAW264.7 macrophages. Among them, compound 4e was found to be the most potent inhibitor, which decreased the production of cytokines in vitro , such as NO, IL-6 and TNF-α, with IC 50 values of 2.64, 4.38 and 5.63 μM, respectively. Further studies showed that compound 4e inhibited cytokines secretion of macrophages through suppressing TLR4/p38 signaling pathway. Additionally, compound 4e showed in vivo anti-inflammatory activity in LPS-induced model of acute lung injury. These data suggested that compound 4e may be a promising lead structure for the treatment of ALI.

A series of novel 4-ferrocenylchroman-2-one derivatives were designed and synthesised to discover potent anti-inflammatory agents for treatment of arthritis. All the target compounds had been screened for their anti-inflammatory activity by evaluating the inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Among them, 4-ferrocenyl-3,4-dihydro-2H-benzo[ g ]chromen-2-one ( 3h ) was found to be the most potent compound in inhibiting the productions of NO with low toxicity. This compound also exhibited significant inhibition of the productions of IL-6 and TNF-α in RAW 264.7 macrophages. Preliminary mechanism studies indicated that compound 3h could inhibit the activation of LPS-induced NF-κB and MAPKs signalling pathways. The in vivo anti-inflammatory effect of this compound was determined in the rat adjuvant-induced arthritis model.

In order to discover novel anti-inflammatory agents, total thirty-seven new resveratrol-based flavonol derivatives were designed and synthesized. All compounds have been screened for their anti-inflammatory activity by evaluating their inhibition effect of LPS-induced NO production in RAW 264.7 macrophages. Their toxicity was also assessed in vitro. Structure-activity relationships (SARs) have been concluded, and finally 2-(2,4-dimethoxy-6-(4-methoxystyryl)phenyl)-3-hydroxy-4H-chromen-4-one was found to be the most active scaffold with low toxicity. This compound could significantly decrease productions of NO, IL-6 and TNF-α with IC 50 values of 1.35, 1.12 and 1.92 μM, respectively in RAW 264.7 macrophages. Preliminary mechanism studies indicated that it could inhibit the expression of TLR4 protein, resulting in activation of the NF-ĸB cell signaling pathway. The in vivo anti-inflammatory activity of this compound could reduce pulmonary inflammation by mouse model of LPS-induced acute lung injury (ALI). We believe these findings would further support studies of rational design of more efficient acute lung injury regulatory inhibitors., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Objective: To investigate the molecular characteristics and intracellular growth ability of Legionella pneumophila (L. pneumophila) strains from 1989 to 2016 in Sichuan Province, China., Methods: Seventy-nine isolates of L. pneumophila were collected from environmental and clinical sources, including cooling towers, hot springs, bath water, fountains, and patients, and identified with 16S rRNA gene analysis and serum agglutination assay. The isolates were then typed by Sequence-Based Typing (SBT), and Genotyping of forty-two LP1 strains were analyzed by means of multiple-locus VNTR analysis with 8 loci (MLVA-8). All strains were further analyzed for two virulence genes: Legionella vir homologue (lvh) and repeats in structural toxin (rtxA). The intracellular growth ability of 33 selected isolates was determined by examining their interaction with J774 cells., Results: All isolates were identified to L. pneumophila including 11 serogroups, among which the main serogroup were LP1, accounting for 54.43%. Thirty-three different sequence types (STs) from five main clonal groups and five singletons were identified, along with 8 different MLVA patterns. Both the lvh and rtxA loci were found in all 79 strains. Thirty isolates showed high intracellular growth ability in J774 cells., Conclusion: L. pneumophila is a potential threat to public health, and effective control and prevention strategies are urgently needed., (Copyright © 2019 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.)