A new species of Svistella Gorochov, 1987 from Xizang, China (Orthoptera, Trigonidiidae, Trigonidiinae).

The genus Svistella Gorochov, 1987 includes 10 species from Asia, with nine documented in China. In this study, a new species, Svistellayayun He, sp. nov., is described from Xizang, China. Morphologically, it resembles S.rufonotata (Chopard, 1932) but can be distinguished by a smaller inner tympanum, dark-brown setae on the 5th segment of the maxillary palp, and a rounded apex on the ectoparamere. To validate our morphological inferences and support the description of S.yayunsp. nov. as a new species, we performed a PCA based on bioacoustics parameters and molecular analysis. All Svistella species documented in China are distinguished by integrating their songs and DNA barcoding.

Comparative study of two models predicting the risk of deep vein thrombosis progression in spinal trauma patients after operation.

OBJECTIVE: Patients with preoperative deep vein thrombosis (DVT) exhibit a notable incidence of postoperative deep vein thrombosis progression (DVTp), which bears a potential for silent, severe consequences. Consequently, the development of a predictive model for the risk of postoperative DVTp among spinal trauma patients is important. METHODS: Data of 161 spinal traumatic patients with preoperative DVT, who underwent spine surgery after admission, were collected from our hospital between January 2016 and December 2022. The least absolute shrinkage and selection operator (LASSO) combined with multivariable logistic regression analysis was applied to select variables for the development of the predictive logistic regression models. One logistic regression model was formulated simply with the Caprini risk score (Model A), while the other model incorporated not only the previously screened variables but also the age variable (Model B). The model's capability was evaluated using sensitivity, specificity, positive predictive value, negative predictive value, accuracy, F1 score, and receiver operating characteristic (ROC) curve. Nomograms simplified and visually presented Model B for the clinicians and patients to understand the predictive model. The decision curve was used to analyze the clinical value of Model B. RESULTS: A total of 161 DVT patients were enrolled in this study. Postoperative DVTp occurred in 48 spinal trauma patients, accounting for 29.81% of the total patient enrolled. Model A inadequately predicted postoperative DVTp in spinal trauma patients, with ROC AUC values of 0.595 for the training dataset and 0.593 for the test dataset. Through the application of LASSO regression and multivariable logistic regression, a screening process was conducted for seven risk factors: D-dimer, blood platelet, hyperlipidemia, blood group, preoperative anticoagulant, spinal cord injury, lower extremity varicosities. Model B demonstrated superior and consistent predictive performance, with ROC AUC values of 0.809 for the training dataset and 0.773 for the test dataset. According to the calibration curves and decision curve analysis, Model B could accurately predict the probability of postoperative DVTp after spine surgery. The nomograms enhanced the interpretability of Model B in charts and graphs. CONCLUSIONS: In summary, we established a logistic regression model for the accurate predicting of postoperative deep vein thrombosis progression in spinal trauma patients, utilizing D-dimer, blood platelet, hyperlipidemia, blood group, preoperative anticoagulant, spinal cord injury, lower extremity varicosities, and age as predictive factors. The proposed model outperformed a logistic regression model based simply on CRS. The proposed model has the potential to aid frontline clinicians and patients in identifying and intervening in postoperative DVTp among traumatic patients undergoing spinal surgery.

Microbial community and gene dynamics response to high concentrations of gadolinium and sulfamethoxazole in biological nitrogen removal system.

The impact of high antibiotic and heavy metal pollution levels on biological nitrogen removal in wastewater treatment plants (WWTPs) remains poorly understood, posing a global concern regarding the issue spread of antibiotic resistance induced by these contaminants. Herein, we investigated the effects of gadolinium (Gd) and sulfamethoxazole (SMX), commonly found in medical wastewater, on biological nitrogen removal systems and microbial characteristics, and the fate of antibiotic resistance genes (ARGs), metal resistance genes (MRGs), and mobile genetic elements (MGEs). Our findings indicated that high SMX and Gd(III) concentrations adversely affected nitrification and denitrification, with Gd(III) exerting a strong inhibitory effect on microbial activity. Metagenomic analysis revealed that high SMX and Gd(III) concentrations could reduce microbial diversity, with Thauera and Pseudomonas emerging as dominant genera across all samples. While the relative abundance of most ARGs decreased under single Gd(III) stress, MRGs increased, and nitrification functional genes were inhibited. Conversely, combined SMX and Gd(III) pollution increased the relative abundance of intl1. Correlation analysis revealed that most genera could host ARGs and MRGs, indicating co-selection and competition between these resistance genes. However, most denitrifying functional genes exhibited a positive correlation with MRGs. Overall, our study provides novel insights into the impact of high concentrations of antibiotics and heavy metal pollution in WWTPs, and laying the groundwork for the spread and proliferation of resistance genes under combined SMX and Gd pollution.

Remodeling tumor immunosuppression with molecularly imprinted nanoparticles to enhance immunogenic cell death for cancer immunotherapy.

Insufficient tumor accumulation and distribution of immunogenic cell death (ICD) inducer as well as low antitumor immunity severely restrict the therapeutic efficacy of tumor immunotherapy. Tumor associated fibroblasts (TAFs) are important in tumor extracellular matrix (ECM) remodeling and immune evasion. Reprogramming tumor immunosuppressive microenvironment via TAFs regulation might present a promising way for enhanced ICD effect and complete tumor elimination. In this study, TAFs derived tryptase imprinted nanoparticles (DMSN@MIPs) are developed to modulate TAFs and improve tumor immunotherapy effect of doxorubicin liposomes (DOX/LIP). Tryptase (TPS), secreted by mast cells, are found to support tumor growth via transcriptionally activating TAFs to an activated state with increased expression of fibroblast activation marker α-smooth muscle actin (α-SMA). DMSN@MIPs canbe used as artificial antibodies, which effectively neutralize TPS, reduce TAFs activation, promote intra-tumor penetration of DOX/LIP and enhance ICD effect induced by DOX/LIP. In addition, the combined administration system remodels immunosuppressive microenvironment, which not only significantly up-regulates immune cells (DC cells, CD8+T cells, NK cells), but also significantly down-regulates immunosuppressive cells (Treg cells, MDSCs cells). Our results support the DMSN@MIPs canbe a promising approach to improve ICD efficacy in cancer immunotherapy.

Are the recently described fossil Mole Crickets of Myanmar amber real gryllotalpids? (Orthoptera: Gryllotalpidae & Gryllidae).

We report five new Myanmar amber specimens attributable to "Mole Cricket" †Pherodactylus rectanguli n. comb., hitherto regarded as a Mole Cricket (Orthoptera: Grylloptalpidae). The new material includes two adult males, two adult females, and one nymph. The specimens are redescribed, and additional new characters are provided for their delimitation and corresponding species identification. We carry out a comparison between these new specimens with other taxa of mole crickets from Myanmar amber and extant true crickets. The result indicates that some species merely represent different nymphal development stages or adults of †Pherodactylus rectanguli n. comb., however, they were misidentified as different species. We also treated genera †Tresdigitus n. syn. and †Chunxiania n. syn. as synonyms of genus †Pherodactylus Poinar, Su & Brown, 2020, and treat †Tresdigitus gracilis Jiang, Xu, Jarzembowski & Xiao, 2022 n. syn. and †Chunxiania fania n. syn. as synonyms of †Pherodactylus rectanguli n. comb. †Burmagryllotalpa longa is valid, because its shape of the pronotum curved without lateral carinae. The morphological convergences and specializations of subterranean dwelling species are discussed. The robust fore tibia and long apical spurs of †P. micromorphus, †P. rectanguli n. comb. and †B. longa are insufficient evidence for an assignment to the family Gryllotalpidae. Instead, we suggest place them into the subfamily Gryllinae (Gryllidae), tribe Sclerogryllini, and group them into their own subtribe Pherodactylina n. subtr.. A key to the identification of recent and fossil Sclerogryllini is also provided. Their taxonomy and morphology are discussed.

Substrate Stiffness Regulates the Proliferation and Apoptosis of Periodontal Ligament Cells through Integrin-Linked Kinase ILK.

The hallmark of orthodontic tooth movement (OTM) is time-consuming during clinical treatments. The acceleration of OTM through modulating proliferation and apoptosis of periodontal ligament cells (PDLCs) possesses the potential application in clinical treatments. Here, we established an in vitro model with a graded increase in substrate stiffness to investigate the underlying mechanism of proliferation and apoptosis of PDLCs. The role of the integrin-linked kinase (ILK) in response to substrate stiffness was investigated by the depletion model of PDLCs. We found that the proliferation and apoptosis of PDLCs show a stiffness-dependent property with stiffer substrates favoring increased bias at the transcript level. Depleting integrin-linked kinase diluted the correlation between PDLCs behaviors and substrate stiffness. Our results suggest that ILK plays a significant role in modulating PDLC proliferation and apoptosis and can serve as a potential target for accelerating OTM.

Hyoid bone position in subjects with different facial growth patterns of different dental ages.

OBJECTIVE: To explore the correlation between hyoid bone (HB) positions and facial growth patterns (facial patterns) in Chinese adults; to identify any significant difference in HB position among subjects with different facial patterns in various dental ages. METHODS: Lateral cephalometric radiographs of 197 Chinese subjects were divided into nine groups based on their dental ages and facial patterns. Seven measurements were used to define HB position. Regression, correlation analyses, and one-way ANOVA were carried out. RESULTS: Significant correlations were found between facial patterns and anteroposterior HB positions. The HB was more anterior in the horizontal group after mixed dentition and further away from the mandibular plane in the vertical group of adults. Vertical HB positions were insignificantly different in any stage. CONCLUSION: HB position and facial patterns were correlated. There were significantly different HB positions among people with different facial patterns in various dental ages.

Effect of Hand Hygiene Intervention in Community Kindergartens: A Quasi-Experimental Study.

This study aimed to evaluate the effect of hand hygiene interventions on the overall hand hygiene (HH) status of teaching instruction of hand hygiene in kindergartens, given the vulnerability of kindergarten children and their high risk due to infectious diseases and the current COVID-19 epidemic. We investigated the HH status of teachers from two kindergartens in the same community. The participants were recruited from 28 classes in both kindergartens. After completing the baseline survey, the intervention program consisted of three components: lectures on infectious diseases, lectures on HH, and seven-step hand washing techniques conducted in two kindergartens. The intervention program effectively increased teachers' perceived disease susceptibility (p < 0.05), reduced the total bacterial colonization of children's hands (p < 0.001), and improved the HH environment (p < 0.01). We recommend that health authorities or kindergartens adopt this HH intervention program to effectively improve the HH status in kindergartens and allow for preventive responses to the COVID-19 epidemic or other emerging infectious diseases.

A new species of whip spider, Sarax sinensis sp. nov., from Fujian, China (Arachnida: Amblypygi: Charinidae).

To date, only two whip spider species have been recorded in China. We describe a new species, Sarax sinensis sp. nov., from Fujian, China. This species is morphologically similar to S. ioanniticus (Kritscher, 1959), S. israelensis (Miranda et al., 2016), and S. seychellarum (Kraepelin, 1898), but can be distinguished by the combination of the following characters: 35 segments in leg I tarsus, eight teeth on cheliceral claw, and four dorsal and ventral spines respectively on pedipalp femur. To examine the evolutionary history of S. sinensis sp. nov., we sequenced 12S, 16S, and COI gene regions of our specimens and inferred its phylogenetic position. The inferred phylogenetic trees placed the new species within Sarax, with its closest relative being distributed across the western Asia. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).

CRISPR/Cas9-mediated mutation in auxin efflux carrier OsPIN9 confers chilling tolerance by modulating reactive oxygen species homeostasis in rice.

Phytohormone auxin plays a vital role in plant development and responses to environmental stresses. The spatial and temporal distribution of auxin mainly relies on the polar distribution of the PIN-FORMED (PIN) auxin efflux carriers. In this study, we dissected the functions of OsPIN9, a monocot-specific auxin efflux carrier gene, in modulating chilling tolerance in rice. The results showed that OsPIN9 expression was dramatically and rapidly suppressed by chilling stress (4°C) in rice seedlings. The homozygous ospin9 mutants were generated by CRISPR/Cas9 technology and employed for further research. ospin9 mutant roots and shoots were less sensitive to 1-naphthaleneacetic acid (NAA) and N-1-naphthylphthalamic acid (NPA), indicating the disturbance of auxin homeostasis in the ospin9 mutants. The chilling tolerance assay showed that ospin9 mutants were more tolerant to chilling stress than wild-type (WT) plants, as evidenced by increased survival rate, decreased membrane permeability, and reduced lipid peroxidation. However, the expression of well-known C-REPEAT BINDING FACTOR (CBF)/DEHYDRATION-RESPONSIVE ELEMENT-BINDING PROTEIN 1 (DREB)-dependent transcriptional regulatory pathway and Ca2+ signaling genes was significantly induced only under normal conditions, implying that defense responses in ospin9 mutants have probably been triggered in advance under normal conditions. Histochemical staining of reactive oxygen species (ROS) by 3'3-diaminobenzidine (DAB) and nitroblue tetrazolium (NBT) showed that ospin9 mutants accumulated more ROS than WT at the early stage of chilling stress, while less ROS was observed at the later stage of chilling treatment in ospin9 mutants. Consistently, antioxidant enzyme activity, including catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD), improved significantly during the early chilling treatments, while was kept similar to WT at the later stage of chilling treatment, implying that the enhanced chilling tolerance of ospin9 mutants is mainly attributed to the earlier induction of ROS and the improved ROS scavenging ability at the subsequent stages of chilling treatment. In summary, our results strongly suggest that the OsPIN9 gene regulates chilling tolerance by modulating ROS homeostasis in rice.

Goniurosaurus wangshu sp. nov., a new species of Tiger Gecko from Guangdong, China (Squamata: Eublepharidae).

A new species of Tiger Gecko in the genus Goniurosaurus is described from Guangdong, China. This new species, Goniurosaurus wangshu sp. nov. is the fifth species of Goniurosaurus found in karst topography of Guangdong. It is distinguished morphologically from congeners in this region by the combination of thirteen precloacal pores in male; dorsal ground color of head, body, and limbs in adults yellow; and iris orange. To validate our morphological inferences and support the description of Goniurosaurus wangshu sp. nov. as a new species, we sequenced 16S, CMOS, cytb, and RAG1 gene regions and performed molecular phylogenetic analyses. Phylogenetic analysis places the new species within the G. yingdeensis group and highlights the evolutionary distinction between this new species and other described congeners.

Role of integrin­linked kinase in static compressive stress­induced autophagy via phosphatidylinositol 3 kinase in human periodontal ligament cells.

Orthodontic tooth movement (OTM) is achieved by using mechanical stimuli, which lead to the remodeling of periodontal tissues. Previous findings have demonstrated that autophagy may be one of the cell responses to mechanical stress. As a key structure in the integrin pathway, integrin linked­kinase (ILK) may play a role in the transmission of these mechanical signals. In addition, ILK is an important upstream molecule that regulates autophagy, under the influence of phosphatidylinositol 3 kinase (PI3K). Therefore, exploring the effect of mechanical stress on autophagy and the associated role of ILK/PI3K is of utmost significance to understanding the mechanism behind OTM. In the present study, human periodontal ligament cells (hPDLCs) were embedded into a collagen­alginate complex hydrogel for three­dimensional (3D) culturing. Static compressive stress (2.5 g/cm2) was loaded using the uniform weight method for 5, 15, 30, and 60 min. The autophagy of hPDLCs was detected by the expression of Beclin­1 (BECN1) and ATG­5 using RT­qPCR and LC3, respectively, using immunofluorescence. The results showed that the level of autophagy and gene expression of ILK increased significantly under static compressive stress. In ILK­silenced cells, static compressive stress could also upregulate ILK expression and increase the levels of autophagy. After PI3K inhibition, the increase in the autophagy level and the upregulation of ILK expression disappeared. These findings suggest that static compressive stress can induce autophagy in hPDLCs in a rapid, transient process, regulated by ILK and PI3K. Moreover, this static stress can upregulate ILK expression in a PI3K­dependent manner.

Enhancing TNBC Chemo-immunotherapy via combination reprogramming tumor immune microenvironment with Immunogenic Cell Death.

Tumor-associated fibroblasts (TAFs) play an important role in tumor progression and therapeutic response, especially in the immunosuppressive tumor microenvironment (TME). To remodel immunosuppressive TME of 4T1 tumor, we developed a nano liposome to deliver silybin (SLN, an anti-liver fibrosis Chinese Traditional Medicine). Liposomal silybin (SLN/LIP) possessed a spherical shape with particle sizes of 75.2 nm, high stability, and good accumulation in the tumor site. After treated with SLN/LIP, α-SMA positive TAFs and the deposition of stroma were decreased significantly. SLN/LIP also changed the tumor immune microenvironment through the increase of IFN-γ and IL-12, as well as reduced of TGF-ß, SDF-1, IL6 and TNF-α. Importantly, SLN/LIP enhanced the infiltration of cytotoxic T cells (CTLs) and transformed a "cold" tumor into a "hot" tumor. To achieve the higher antitumor efficacy, an immunogenic cell death (ICD) inducer, liposomal doxorubicin (DOX/LIP) was combined with SLN/LIP. The combination treatment led to trigger immunogenic tumor apoptosis, and enhance antitumor immunity, therefore, improved anti-tumor efficiency, and further prolonged survival duration. The combination of liposomal silybin and liposomal doxorubicin might be a new chemo-immunotherapy approach for triple negative breast cancer (TNBC) tumor treatment.

A new species of whip spider, Weygoldtia hainanensis sp. nov., from Hainan, China (Arachnida: Amblypygi: Charinidae).

To date, only one species of whip spider has been recorded in China. Here, we describe a new species, Weygoldtia hainanensis sp. nov., from Hainan, China. The new species is morphologically similar to W. davidovi (Fage, 1946) and W. consonensis Miranda et al. 2021, but can be distinguished with a combination of the following characters: 26 segments in tibia I, 6-7 teeth on chelicerae, distitibia IV trichobothria sc and sf series each with 10-11 trichobothria. To validate our morphological inferences and support the erection of W. hainanensis sp. nov. as a new species, we sequenced the COI gene region for two individuals and performed molecular phylogenetic analyses. The inferred phylogenetic trees placed the new species within Weygoldtia and highlighted the evolutionary distinction between W. hainanensis sp. nov. and currently described whip spiders. The type specimens are deposited in the Museum of Biology, East China Normal University (ECNU).

Early Clinical Outcomes of Percutaneous Endoscopic Lumbar Discectomy for L4-5 Highly Down-Migrated Disc Herniation: Interlaminar Approach Versus Transforaminal Approach.

OBJECTIVE: This study is a retrospective evaluation of patients with L4-5 highly down-migrated lumbar disc herniation (LDH) operated with interlaminar endoscopic lumbar discectomy (IELD) versus transforaminal endoscopic lumbar discectomy (TELD). METHODS: From January 2015 to December 2018, 77 patients with L4-5 highly down-migrated LDH were divided into 2 groups according to different surgical approaches. There were 40 patients who underwent IELD, and 37 patients who underwent TELD. The operation time, hospital stay, Oswestry Disability Index, clinical outcome according with modified MacNab criteria, Visual Analog Scale (VAS) scores, and complications were compared between the IELD and TELD groups. RESULTS: Seventy-seven patients were included, 40 and 37 patients underwent IELD and TELD, respectively. The IELD and TELD groups both achieved a significant improvement in Oswestry Disability Index, back and leg VAS scores, and clinical outcome postoperation. Mean operating and x-ray times during operation were significantly shorter in the IELD group than in the TELD group (41.8 vs. 50.3, 1.8 vs. 13.7). There were 3 patients who experienced recurrence in the IELD group and 2 in the TELD group. In the TELD group, there were 3 patients who required revision surgery due to incompletely removed disc fragment. All patients in the IELD group were treated successfully. There was no other complication in these cases. CONCLUSIONS: Both IELD and TELD could be a good alternative option for highly down-migrated LDH in L4-L5. IELD may have advantages in operation time and x-ray times during operation compared with TELD.

Folate Modified Long Circulating Nano-Emulsion as a Promising Approach for Improving the Efficiency of Chemotherapy Drugs in Cancer Treatment.

PURPOSE: In order to improve the therapeutic efficiency of the chemotherapeutic drug paclitaxel in tumors, a folate-based Paclitaxel nanoemulsion (FNEs) was developed for tumor targeted treatment. METHODS: In this study, we designed a folate-targeted nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) based on the traditional nanoemulsion using the principle of long-circulation targeting receptor mediated. The nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) was fabricated using high-pressure homogenization with a microfluidizer. RESULTS: The nanoemulsion (folate/PEG-DSPE/nanoemulsion, FNEs) can improve the delivery efficiency of nanocarriers at the tumor site by virtue of the high expression of folate receptors on the tumor surface. Malvern Nanoseries device and transmission electron microscopy (TEM) analyses showed that the nanoemulsions were spherical with an average diameter of 140 nm. The nanoemulsions can effectively carry paclitaxel (PTX) with an encapsulation rate of about 95%. And in vitro experiments have shown that it can efficiently increase the uptake of PTX in 4 T1 breast cancer cells and FNEs had a targeting capability hundredfold higher than that of PTX-loaded nanoemulsions (PTX-NEs) without folate. In vivo experiments have shown that the pharmacokinetic parameters of FNEs were better than those of other PTX groups and FNEs can significantly enhance circulation time in the body of the subcutaneously implanted 4 T1 breast cancer in mice, increase the accumulation of chemotherapy drugs at tumor sites and effectively inhibit tumor growth with lower system toxicity. CONCLUSIONS: This study can effectively improve the therapeutic efficiency of chemotherapy drugs for tumors, and provide an useful reference for solving the problem of low efficacy of chemotherapy drugs in clinical treatment of tumors. Graphical Abstract Schematic representation of Folic acid/PEG-DSPE/nano-emulsion (FNEs) specifically target tumor cells and enhanced anti-tumor effects.

Prediction on treatment improvement in depression with resting state connectivity: A coordinate-based meta-analysis.

BACKGROUND: Previous neuroimaging studies revealed abnormal resting-state functional connectivity between distributed brain areas in patients with major depressive disorder. Those abnormalities were normalized after treatment. Moreover, the functional connectivity could predict clinical response to those treatments. However, there has currently been no meta-analysis to verify these findings. METHODS: The current study aimed to investigate how the resting-state connectivity patterns predict antidepressant response to various treatments across depressive studies by using coordinate-based meta-analysis named activation likelihood estimation. The relevant articles were obtained by searching on PubMed and Web of Science. RESULTS: Following exclusion criteria of inappropriate studies, seventeen papers with 392 individual depressive patients were included. Those articles contained repetitive transcranial magnetic stimulation (rTMS) treatment, pharmacotherapy, cognitive behavioral therapy (CBT), electroconvulsive therapy (ECT) and transcutaneous vagus nerve stimulation in patients with depression. Meta-analysis revealed that clinical response to all treatments could be predicted by baseline default mode network connectivity in patients with depression. The rTMS treatment had larger effect size compared to other treatment strategies. Furthermore, subgroup meta-analysis showed that the baseline connectivity of perigenual anterior cingulate cortex (pgACC) and ventral medial prefrontal cortex could predict symptoms improvement of rTMS treatment. LIMITATIONS: More resting-state connectivity studies of CBT and ECT treatment are needed. CONCLUSIONS: This study highlighted crucial role of DMN, especially the pgACC, in understanding the underlying treatment mechanism of depression.

shRNA knockdown of integrin-linked kinase on hPDLCs migration, proliferation, and apoptosis under cyclic tensile stress.

OBJECTIVE: To investigate the roles of integrin-linked kinase (ILK) in mediating the cell migration, proliferation, and apoptosis of human periodontal ligament cells (hPDLCs) in response to cyclic tensile stress. METHODS: Primary hPDLCs were obtained through the enzyme digestion and tissue culture method. Short hairpin ILK-expressing hPDLCs were constructed using a recombinant lentiviral vector that specifically targeted ILK gene expression. The silencing of the ILK gene was identified by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. The hPDLCs were seeded on a flexible substrate and loaded with cyclic tensile stress at 0.5 Hz for 0, 2, 4, and 8 hr, consecutively, with the Flexcell Tension System. The response of cell migration was tested by the scratch assay. Cell proliferation was characterized by optical density (OD) value of cell counting kit-8 (CCK-8) test and Ki67 mRNA expression of qRT-PCR. Cell apoptosis was determined by flow cytometry and Caspase-3 mRNA expression of qRT-PCR. RESULTS: Knocking down ILK substantially reduces migration and proliferation as well as regulates the sensitivity of hPDLCs to apoptosis under cyclic tensile stress. CONCLUSIONS: ILK can promote the proliferation and migration as well as inhibit apoptosis of hPDLCs under cyclic tensile stress.

Tumor Microenvironment Stimuli-Responsive Nanoparticles for Programmed Anticancer Drug Delivery.

It is well-known that large size nanoparticles stay for a long time in the circulation system, but show poor tissue penetration and low cellular uptake. In order to reconcile the conflicting needs for extended circulation time, extensive tumor tissue penetration, and enhanced cellular uptake for nanodrug delivery systems, we designed DOX-containing hypersensitive nanoparticles that responded to the tumor microenvironment for programmed DOX delivery. A supersensitive polymer material, poly(2-ethyl-2-oxazoline)-poly(methacryloyl sulfadimethoxine), was synthesized (PEOz-b-PSD, pKa = 6.96). At the physiological environment, PEOz-b-PSD and polyamidoamine/DOX (PAMAM/DOX) can form nanoparticles, PEOz-b-PSD/PAMAM/DOX (PEPSD/PAM/DOX), via electrostatic adsorption. The PEPSD/PAM/DOX has an intact structure, which can prolong circulation time. While in the tumor environment, the PEOz-b-PSD was rapidly protonated and showed charge reversal, leading the detachment of PEOz-b-PSD from the nanoparticles; then the large size nanoparticles with a negative charge (PEPSD/PAM/DOX) instantaneously turn into positively charged ultrafine nanoparticles. The sudden inversion of size and charge can effectively improve tumor accumulation and internal penetration. After entering tumor cells, nanoparticles can release drugs quickly through the action of a PAMAM proton sponge, resulting in enhanced tumor inhibition. Our results proved that the programmed nanoparticles could remarkably enhance the in vivo antitumor efficacy and reduce cardiotoxicity of DOX. This study designed ultrasensitive nanoparticles in the tumor microenvironment, which appear to be beneficial for enhancing the treatment efficacy of DOX in solid tumors.

Astrocytic YAP Promotes the Formation of Glia Scars and Neural Regeneration after Spinal Cord Injury.

Yes-associated protein (YAP) transcriptional coactivator is negatively regulated by the Hippo pathway and functions in controlling the size of multiple organs, such as liver during development. However, it is not clear whether YAP signaling participates in the process of the formation of glia scars after spinal cord injury (SCI). In this study, we found that YAP was upregulated and activated in astrocytes of C57BL/6 male mice after SCI in a Hippo pathway-dependent manner. Conditional knockout (KO) of yap in astrocytes significantly inhibited astrocytic proliferation, impaired the formation of glial scars, inhibited the axonal regeneration, and impaired the behavioral recovery of C57BL/6 male mice after SCI. Mechanistically, the bFGF was upregulated after SCI and induced the activation of YAP through RhoA pathways, thereby promoting the formation of glial scars. Additionally, YAP promoted bFGF-induced proliferation by negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Finally, bFGF or XMU-MP-1 (an inhibitor of Hippo kinase MST1/2 to activate YAP) injection indeed activated YAP signaling and promoted the formation of glial scars and the functional recovery of mice after SCI. These findings suggest that YAP promotes the formation of glial scars and neural regeneration of mice after SCI, and that the bFGF-RhoA-YAP-p27Kip1 pathway positively regulates astrocytic proliferation after SCI.SIGNIFICANCE STATEMENT Glial scars play critical roles in neuronal regeneration of CNS injury diseases, such as spinal cord injury (SCI). Here, we provide evidence for the function of Yes-associated protein (YAP) in the formation of glial scars after SCI through regulation of astrocyte proliferation. As a downstream of bFGF (which is upregulated after SCI), YAP promotes the proliferation of astrocytes through negatively controlling nuclear distribution of p27Kip1 mediated by CRM1. Activation of YAP by bFGF or XMU-MP-1 injection promotes the formation of glial scar and the functional recovery of mice after SCI. These results suggest that the bFGF-RhoA-YAP-p27Kip1 axis for the formation of glial scars may be a potential therapeutic strategy for SCI patients.