Evaluation of illness severity of neonate infectious pneumonia and neurobehavioral development through ultrasonography under adaption algorithm.

OBJECTIVES: To explore the diagnostic effect of ultrasound imaging on the illness severity, and to analyze neurobehavioral development of neonates with Infectious Pneumonia (IPN), Self- Adaptation (SD), and Spatial Smoothing (SS) technologies were adopted to build SDSS. Then, the WFFSF algorithm based on Wiener Filtering (WF) and Feature Space Fusion (FSF) and the SNRP-FSF algorithm based on Signal-to-noise ratio post-filtering (SNRP) and FSF were introduced for comparison. METHODS: One hundred and thirty-two neonates were divided into group without respiratory failure (S1) and respiratory failure group (S2). The study was conducted from March 2018 to July 2020. According to scoring systems for neonatal critically illness, they were divided into non-severe group (W1), severe group (W2), and extremely-severe group (W3). According to the Scale of Child Development Center of China (CDCC), they were divided into a normal neurobehavioral developmental group (P1) and an abnormal neurobehavioral developmental group (P2). RESULTS: The normalized mean square distance l and normalized mean absolute distance f of SDSS algorithm were significantly lower than that of WFFSF algorithm and SNRP-FSF algorithm, and the peak signal-to-noise ratio (PSNR) was significantly higher than that of WFFSF algorithm and SNRP-FSF algorithm (P<0.05). The lung ultrasound score (40.62±7.22%) of S1 was greatly higher than S2 group (28.47±6.29%) (P<0.05); the lung ultrasound score (39.13±8.25) in W1 was greatly higher than W2 (27.28±6.39) and W3 groups (14.33±7.03); neonates in group W2 had higher lung ultrasound scores than W3 (P<0.05), and lung ultrasound scores in P1 (42.57±8.58) was greatly higher than that the P2 group (26.49±6.09). CONCLUSION: In contrast with traditional algorithms, the SDSS algorithm based on AD has a better reconstruction effect on neonatal IPN ultrasound images. The lung ultrasound score can clearly indicate the severity of the disease and neurobehavioral development of neonate IPN, and the lung ultrasound score is negatively correlated with the severity of the child's disease and the abnormality of neurobehavioral development.

Targeting STAT3 by a small molecule suppresses pancreatic cancer progression.

Pancreatic cancer is lethal in over 90% of cases since it is resistant to current therapeutic strategies. The key role of STAT3 in promoting pancreatic cancer progression has been proven, but effective interventions that suppress STAT3 activities are limited. The development of novel anticancer agents that directly target STAT3 may have potential clinical benefits for pancreatic cancer treatment. Here, we report a new small-molecule inhibitor (N4) with potent antitumor bioactivity, which inhibits multiple oncogenic processes in pancreatic cancer. N4 blocked STAT3 and phospho-tyrosine (pTyr) peptide interactions in fluorescence polarization (FP) assay, specifically abolished phosphor-STAT3 (Tyr705), and suppressed expression of STAT3 downstream genes. The mechanism involved the direct binding of N4 to the STAT3 SH2 domain, thereby, the STAT3 dimerization, STAT3-EGFR, and STAT3-NF-κB cross-talk were efficiently inhibited. In animal models of pancreatic cancer, N4 was well tolerated, suppressed tumor growth and metastasis, and significantly prolonged survival of tumor-bearing mice. Our results offer a preclinical proof of concept for N4 as a candidate therapeutic compound for pancreatic cancer.

Interesting new Chinese species of Leptoceridae and Odontoceridae (Insecta: Trichoptera) from several recent collecting efforts.

In contravention of Article 16.4.2 of the International Code of Zoological Nomenclature (International Trust for Zoological Nomenclature 1999), the repository for the holotypes of these species was not mentioned by Yang et al. (2020), such that the names proposed for these species are presently nomina nuda.

Interesting new Chinese species of Leptoceridae and Odontoceridae (Insecta: Trichoptera) from several recent collecting efforts.

Nine new species of caddisflies are described from southeastern and central China, including 7 species of Leptoceridae: Ceraclea (Ceraclea) megalophyllon Yang Morse sp. n., C. (Athripsodina) aerumnula Yang Morse sp. n., C. (Ath.) lamellata Yang Hu sp. n., Oecetis (Oecetis) discedens Yang Morse sp. n., Oe. (Pleurograpta) spinellosa Yang Hu sp. n., Setodes charax Yang Morse sp. n., and S. scutatus Yang Morse sp. n. Two species of Odontoceridae also are included: Phraepsyche acuminata Yang Morse sp. n. and Psilotreta longicornis Yang Morse sp. n. The male genitalia of all species and female genitalia of C. megalophylla, C. lamellata, Oecetis discedens, and Oe. spinellosa are figured.

Reversal of Age-Related Changes in Cortical Sound-Azimuth Selectivity with Training.

The compromised abilities to understand speech and localize sounds are two hallmark deficits in aged individuals. Earlier studies have shown that age-related deficits in cortical neural timing, which is clearly associated with speech perception, can be partially reversed with auditory training. However, whether training can reverse aged-related cortical changes in the domain of spatial processing has never been studied. In this study, we examined cortical spatial processing in ~21-month-old rats that were trained on a sound-azimuth discrimination task. We found that animals that experienced 1 month of training displayed sharper cortical sound-azimuth tuning when compared to the age-matched untrained controls. This training-induced remodeling in spatial tuning was paralleled by increases of cortical parvalbumin-labeled inhibitory interneurons. However, no measurable changes in cortical spatial processing were recorded in age-matched animals that were passively exposed to training sounds with no task demands. These results that demonstrate the effects of training on cortical spatial domain processing in the rodent model further support the notion that age-related changes in central neural process are, due to their plastic nature, reversible. Moreover, the results offer the encouraging possibility that behavioral training might be used to attenuate declines in auditory perception, which are commonly observed in older individuals.

A novel BMI-1 inhibitor QW24 for the treatment of stem-like colorectal cancer.

BACKGROUND: Cancer-initiating cell (CIC), a functionally homogeneous stem-like cell population, is resonsible for driving the tumor maintenance and metastasis, and is a source of chemotherapy and radiation-therapy resistance within tumors. Targeting CICs self-renewal has been proposed as a therapeutic goal and an effective approach to control tumor growth. BMI-1, a critical regulator of self-renewal in the maintenance of CICs, is identified as a potential target for colorectal cancer therapy. METHODS: Colorectal cancer stem-like cell lines HCT116 and HT29 were used for screening more than 500 synthetic compounds by sulforhodamine B (SRB) cell proliferation assay. The candidate compound was studied in vitro by SRB cell proliferation assay, western blotting, cell colony formation assay, quantitative real-time PCR, flow cytometry analysis, and transwell migration assay. Sphere formation assay and limiting dilution analysis (LDA) were performed for measuring the effect of compound on stemness properties. In vivo subcutaneous tumor growth xenograft model and liver metastasis model were performed to test the efficacy of the compound treatment. Student's t test was applied for statistical analysis. RESULTS: We report the development and characterization of a small molecule inhibitor QW24 against BMI-1. QW24 potently down-regulates BMI-1 protein level through autophagy-lysosome degradation pathway without affecting the BMI-1 mRNA level. Moreover, QW24 significantly inhibits the self-renewal of colorectal CICs in stem-like colorectal cancer cell lines, resulting in the abrogation of their proliferation and metastasis. Notably, QW24 significantly suppresses the colorectal tumor growth without obvious toxicity in the subcutaneous xenograft model, as well as decreases the tumor metastasis and increases mice survival in the liver metastasis model. Moreover, QW24 exerts a better efficiency than the previously reported BMI-1 inhibitor PTC-209. CONCLUSIONS: Our preclinical data show that QW24 exerts potent anti-tumor activity by down-regulating BMI-1 and abrogating colorectal CICs self-renewal without obvious toxicity in vivo, suggesting that QW24 could potentially be used as an effective therapeutic agent for clinical colorectal cancer treatment.

Synthesis of Cyanoenone-Modified Diterpenoid Analogs as Novel Bmi-1-Mediated Antitumor Agents.

Bmi-1 is overexpressed in colorectal cancer (CRC) and served as a novel therapeutic target for the treatment of CRC. A series of novel cyanoenone-modified diterpenoid analogs was synthesized and investigated for their antiproliferative activity against CRC cells. The results showed that most of these compounds exhibited potent antiproliferative and Bmi-1 inhibitory activity. Among them, the most active compound 33 (SH498) showed more potent antiproliferative activity than the positive control compound PTC-209. These synthetic diterpenoid analogs were less toxic for normal human fibroblasts (HAF) than for CRC cells. Especially 33, its selectivity index (SI) between HAF and tumor cells was 7.3-13.1, which was much better than PTC-209. The polycomb repressive complex 1 (PRC1) complex, transwell migration, colony formation, cancer stem cell proliferation, and apoptosis assays of 33 were performed on CRC cell lines. The in vivo antitumor effect of 33 was also observed in HCT116 tumor-bearing mice.

Cholesterol Modification of Smoothened Is Required for Hedgehog Signaling.

Hedgehog (Hh) has been known as the only cholesterol-modified morphogen playing pivotal roles in development and tumorigenesis. A major unsolved question is how Hh signaling regulates the activity of Smoothened (SMO). Here, we performed an unbiased biochemical screen and identified that SMO was covalently modified by cholesterol on the Asp95 (D95) residue through an ester bond. This modification was inhibited by Patched-1 (Ptch1) but enhanced by Hh. The SMO(D95N) mutation, which could not be cholesterol modified, was refractory to Hh-stimulated ciliary localization and failed to activate downstream signaling. Furthermore, homozygous SmoD99N/D99N (the equivalent residue in mouse) knockin mice were embryonic lethal with severe cardiac defects, phenocopying the Smo-/- mice. Together, the results of our study suggest that Hh signaling transduces to SMO through modulating its cholesterylation and provides a therapeutic opportunity to treat Hh-pathway-related cancers by targeting SMO cholesterylation.

New species of microcaddisflies from China (Trichoptera: Hydroptilidae).

Five new species of hydroptilids in four genera are described from China, including three new species in Hydroptilinae: Agraylea dactylina n. sp., Allotrichia rhynchophyllum n. sp., and Microptila hamatilis n. sp.; and two new species in Stactobiinae: Stactobiella mutica n. sp. and Stactobiella parallelica n. sp. New records are given for Stactobiella biramosa Martynov 1929 and Pseudoxyethira thingana (Oláh) 1989. Genera Agraylea, Allotrichia, Stactobiella, and Microptila are new to Chinese fauna.

Synthesis of novel diterpenoid analogs with in-vivo antitumor activity.

A lead compound 7 has antitumor effect, which was discovered by screening our small synthetic natural product-like compound (NPL) library. Based on the lead compound, a series of novel tricyclic diterpene analogs were synthesized and investigated for their activity against the growth of various tumor cell lines using the sulforhodamine B (SRB) assay. To our delight, most aromatic amide compounds exhibited more potent antitumor activity than the lead compound. The most active compound 19 (QW30) showed an average IC50 0.33 µM, which was 15-fold more potent than the lead compound. Most of the compounds with potent antitumor activity displayed less toxic on normal human fibroblasts (HAF) in comparison with the tumor cell lines. Especially 19, its selectivity indexes (SI) between HAF and cancer cell lines was 17.3 times better than the positive control compound podophyllotoxin. The apoptosis, colony formation and transwell migration assays of 7 and 19 were performed on T47D cell line. The in-vivo antitumor effect of 19 was also observed in T47D tumor-bearing mice without obvious toxicity.

Design, synthesis and biological evaluation of tricyclic diterpene derivatives as novel neuroprotective agents against ischemic brain injury.

Lead compound 7 has neuroprotective effects, and it was discovered by screening a small synthetic natural product-like (NPL) library. Based on the lead, a series of tricyclic diterpene derivatives was designed and synthesized, and their neuroprotective effects were further evaluated against glutamate-, oxygen and glucose deprivation (OGD)- and nutrient deprivation-induced neuronal injury using cell-based assays. To our delight, most of these synthetic compounds exhibited increased neuroprotective effects and blood-brain barrier (BBB) permeability without cellular toxicity. The most potent compound, compound 30, showed significantly improved neuroprotection against neuronal injury in primary neurons. Furthermore, compound 30 exhibited remarkable neuroprotection in transient middle cerebral artery occlusion (tMCAO) rats by reducing their infarct sizes and neurological deficit scores. A mechanistic exploration using in vitro and in vivo experiments showed that the neuroprotection of these compounds was at least partly mediated by improving the levels of glutathione (GSH), superoxide dismutase (SOD) and heme oxygenase-1 (HO-1) protein. Therefore, these tricyclic diterpene derivatives could be used as promising leads for the development of a new type of neuroprotective agents against ischemic brain injury.

The genus Nyctiophylax Brauer in China (Trichoptera, Polycentropodidae).

Currently, 8 species of the genus Nyctiophylax Brauer are known from China. Examination of material collected from Guangdong, Guangxi, Jiangxi and Sichuan Provinces during 2004-2005 has revealed 4 new species and 2 new records of this genus, bringing the number of Chinese Nyctiophylax species to 14. Newly described species include: Nyctiophylax (Paranyctiophylax) crinalis n. sp., N. (P.) dactylatus n. sp., N. (P.) orbicularis n. sp., and N. (P.) macrorrhinus n. sp. Nyctiophylax (Paranyctiophylax) sagax Mey and N. (N.) amphonion Malicky & Chantaramongkol are newly recorded for the Chinese fauna, which are re-illustrated and re-described for clear comparisons. The additional collection sites for the previously described species are provided. 

New species of Plectrocnemia and Nyctiophylax (Trichoptera, Polycentropodidae) from China.

Four new species of genus Plectrocnemia and 4 new species of genus Nyctiophylax are described, namely: Plectrocnemia verticalissp. n.; Plectrocnemia acuminatasp. n.; Plectrocnemia cryptoparameresp. n.; Plectrocnemia qianshanensissp. n.; Nyctiophylax (Nyctiophylax) senticosussp. n.; Nyctiophylax (Paranyctiophylax) gracilissp. n.; Nyctiophylax (Paranyctiophylax) pungenssp. n.; and Nyctiophylax (Paranyctiophylax) auriculatussp. n.

[Stream health assessment using a benthic-index of biotic integrity in Xitiaoxi Stream, Zhejiang Province, China].

Stream macro-invertebrate assemblages were collected from 64 stream sites in Xitiaoxi Stream, Anji County, Zhejiang Province, China. Thirty-six candidate metrics were evaluated stepwise by distributing range analysis, discriminatory power analysis, and Pearson's correlation analysis. The B-IBI was composed of seven metrics: total taxa, EPT taxa, Coleoptera %, three dominant taxa, Hydropsychidae (Trichoptera) %, filterers %, and Biotic Index (BI). The ratio scoring method was used to transform the value of each metric into a uniform score. A variability coefficient method and an entropy method were used to calculate the weight value of each metric of the B-IBI. The measurement accuracy of the health criteria for the B-IBI derived from all sample data was better than that from only reference data. The entropy method had a higher accuracy (92.9%) than the sum total score method (85.7%) and the variability coefficient method (78.5%) in discriminating stressed and reference sites. The B-IBI health criteria for Xitiaoxi Stream were: B-IBI > 0.69 = healthy, 0.52 - 0.68 = sub-healthy, 0.35-0.51 = good-fair, 0.18-0.34 = fair, B-IBI < 0.17 = poor. The Pearson's correlation analysis between B-IBI and chemical-physical variables showed that the B-IBI strongly corresponded with the habitat quality index (r = 0.62, p < 0.01), water temperature (r = -0.64, p < 0.01), and altitude (r = 0.64, p < 0.01). Our results suggest that the B-IBI is a good indicator in stream health assessment and should be used in water resource management in China.