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In this work, Chitosan-grafted-chlorogenic acid (CS-g-CA) was prepared by the carbodiimide method. The purpose of this study was to investigate the antibacterial and anti-biofilm activity of CS-g-CA against Staphylococcus aureus (S. aureus). The minimum inhibitory concentration (MIC) of CS-g-CA against S. aureus was identified as 0.625 mg/mL. S. aureus treated with 1/2 × MIC of CS-g-CA had a longer logarithmic growth phase than that of the CK group, while 1 × MIC and 2 × MIC inhibited the growth of bacteria. The damaging effect of CS-g-CA on bacterial cells was analyzed by measuring the activity of cellular antioxidant enzymes (Catalase (CAT) and Glutathione peroxidase (GSH-Px)) and intracellular enzymes (alkaline phosphatase (AKPase) and adenosine triphosphatase (ATPase)). The results of DNA gel electrophoresis illustrated that CS-g-CA disrupted the normal metabolism of bacteria. Scanning electron microscopy (SEM) results showed that S. aureus shrank and died under CS-g-CA treatment. 1 × MIC of CS-g-CA can significantly inhibit the formation of biofilms, and 1/2 × MIC of CS-g-CA control the swimming speed of S. aureus. In addition, 77.53% mature biofilm and 60.62% extracellular polysaccharide (EPS) in the mature biofilm of S. aureus were eradicated by CS-g-CA at 2 × MIC. Confocal laser scanning microscopy (CLSM) observation further confirmed these results. Therefore, CS-g-CA was an antimicrobial and antibiofilm agent to control S. aureus, which can effectively controlling the growth of S. aureus in food, thereby preventing the occurrence of food-borne diseases.

IntroductionPheochromocytomas and paragangliomas (PCC/PGL) are rare neuroendocrine tumors and can secrete catecholamine. Previous studies have found that SDHB immunohistochemistry (IHC) can predict SDHB germline gene mutation, and SDHB mutation is closely associated with tumor progression and metastasis. This study aimed to clarify the potential effect of SDHB IHC as a predictive marker for tumor progression in PCC/PGL patients.MethodsWe included PCC/PGL patients diagnosed in Ruijin Hospital, Shanghai Jiao Tong University School of Medicine from 2002 to 2014 for retrospective analysis and discovered that SDHB (-) staining patients had poorer prognoses. Then we examined SDHB protein expression by IHC on all tumors in the prospective series, which was composed of patients from 2015 to 2020 in our center.ResultsIn the retrospective series, the median follow-up was 167 months, and during follow-up, 14.4% (38/264) patients developed metastasis or recurrence, and 8.0% (22/274) patients died. Retrospective analysis revealed that 66.7% (6/9) of participants in the SDHB (-) group and 15.7% (40/255) of those in the SDHB (+) group developed progressive tumors (OR: 10.75, 95% CI: 2.72-52.60, P=0.001), and SDHB (-) was independently associated with poor outcomes after adjusting by other clinicopathological parameters (OR: 11.68, 95% CI: 2.58-64.45, P=0.002). SDHB (-) patients had shorter disease-free survival (DFS) and overall survival (OS) (PConclusionsOur findings demonstrated patients with SDHB (-) tumors had a higher possibility of poor outcomes, and SDHB IHC can be regarded as an independent biomarker of prognosis in PCC/PGL.

The Qingyihuaji decoction (QYHJ) is composed of seven herbs: Scutellaria barbata D.Don (Banzhilian, HSB), Gynostemma pentaphyllum (Thunb.) Makino (Jiaogulan, GP), Oldenlandia diffusa (Willd.) Roxb. (Baihuasheshecao, HDH), Ganoderma lucidum (Leyss. ex Fr.) Karst. (Lingzhi, GL), Myristica fragrans Houtt. (Doukou, AK), and Amorphophallus kiusianus (Makino) Makino (Sheliugu, RA), and Coix lacryma-jobi var. ma-yuen (Rom.Caill.) Stapf (Yiyiren, CL). QYHJ has been reported to exhibit clinical efficacy in the treatment of pancreatic adenocarcinoma (PAAD). However, the molecular mechanism remains unclear.This study explores the therapeutic mechanism of QYHJ in the treatment of PAAD using network pharmacology to identify related targets and pathways in vivo and in vitro.The bioactive compounds of QYHJ were retrieved and screened using the ADME network pharmacology approach, followed by compound-target prediction and overlapping genes between PAAD oncogenes and QYHJ target genes. The compound-target-pathway network was established using The KEGG pathway, GO analysis, and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) analysis to identify potential action pathways. The effects of QYHJ on PAAD were evaluated in vivo and in vitro, and the predicted targets and potential pathways related to QYHJ in PAAD treatment were evaluated using qRT-PCR and immunoblotting.A total of 68 bioactive compounds of QYHJ fulfilled the ADME screening criterion, and their respective 242 target genes were retrieved. The compound-target-disease network identified 11 possible target genes. The KEGG pathway analysis showed significant enrichment of pathways in cancers, involving regulating cancer-related pathways of inflammation, oxidative stress, and apoptosis. Furthermore, QYHJ inhibited PAAD growth in vivo; suppressed cell proliferation, invasion, and migration of PAAD; and induced cellular apoptosis in vitro. The qRT-PCR results showed that QYHJ suppressed the mRNA expression of ICAM1, VCAM1, and Bcl2, and increased that of HMOX1 and NQO1. Immunoblotting revealed changes in the PI3K/AKT/mTOR, Keap1/Nrf2/HO-1/NQO1, and Bcl2/Bax pathways upon QYHJ treatment.QYHJ can suppress PAAD growth and progression through various mechanisms, including anti-inflammation and apoptosis-induction.

Fractures are widely distributed in coal, and studying the seepage characteristics of fluids in Y-shaped fractures is of great significance for unconventional natural gas extraction and prevention of gas disasters. In this paper, based on the W-M fractal function, a Y-shaped fracture model with different roughness is established. The different seepage characteristics caused by rough morphology characteristics and roughness difference of the Y-shaped fracture is systematically studied, and the influence of fracture roughness on fracture seepage characteristics and fracture roughness difference on fracture fluid competitive diversion capacity are discussed. The results show that the fracture roughness is an important factor affecting the seepage characteristics of the fracture. When the fractal dimension of the fracture is identical, the outlet flow rate, velocity and Re all increase with the increase of the inlet pressure, and the flow regime is unchanged. The increase in the fracture roughness will lead to significant momentum loss and enhance the flow resistance of the fracture. In addition, the roughness difference between the branch fractures of the Y-shaped fracture is the key factor to control the fluid competitive diversion phenomenon. The larger the roughness difference between the two branch fractures, the greater difference in flow velocity, and the more significant change in flow rate proportion. As the inlet pressure increases, the two branch fractures Re gradually increases and Eu decreases, which smooth branch fracture Re grows faster, its Eu is much smaller than rough branch fracture Eu, and the smooth branch fracture competitive diversion capacity is enhanced. These results can provide new insights for the exploitation of underground fluid resources.

The mechanics of the microenvironment, particularly the extracellular matrix, dictate cellular functions, including cell survival, apoptosis, proliferation, differentiation and many types of morphogenesis, through mechanosensing and mechanotransduction. All these processes depend on the temporal balance in cellular metabolism; however, the mechanisms by which cell metabolism is controlled and adapted to changes in the mechanical environment are not completely clear. Here, we report that mechanical stiffness mediates triglyceride (TG) metabolism in chondrocyte model. Cellular TG contents were first shown to be coupled to mechanical stiffness. Specifically, the synthesis and lipolysis of TGs were mechanically regulated by fatty acid-binding protein 3 (FABP3) and cytochrome p450 1b1 (cyp1b1), respectively. The shift from synthesis to lipolysis was mediated by the regulatory FZD7-c-Myc-PPARα/PGC1 signaling axis. The final metabolomic analysis confirmed that the products identified were from TG metabolism. This study reveals crosstalk between microenvironment mechanics and lipid metabolism and identifies the key roles of mediators in this process.

Background: Complete uterine rupture (CUR) is a rare but severe obstetric complication. We explored the characteristics of CUR and compared the maternal and perinatal outcomes of different types of CUR. Methods: This was a hospital-based multicenter retrospective cohort study. We consecutively enrolled women with surgically confirmed CUR from 22 tertiary hospitals in China between January 1, 2004 and January1, 2019. CUR patients were divided into CS (cesarean section)-scarred, non-CS-scarred and unscarred groups. Characteristics and outcomes of CUR patients were compared appropriately. Findings: There were 201 women with CUR. CS-scarred CUR was the most common type (130, 64.7%), followed by unscarred CUR (47, 23.4%) and non-CS-scarred CUR (24, 12%). CUR resulted in 4 maternal deaths (2%).An increase in severe postpartum hemorrhage was observed in the following order: CS-scarred CUR < non-CS-scarred CUR< unscarred CUR. There were 210 fetuses and newborns including 9 twins. The fetal and perinatal mortality rates were 31% and 24.3% respectively. 25 of the newborns had severe neonatal asphyxia, and 74 newborns required NICU admission. 13 infants were diagnosed with hypoxic ischemic encephalopathy. Increases in fetal death, perinatal death and NICU admission were observed in the following order: CS-scarred CUR < non-CS-scarred CUR < unscarred CUR. Interpretation: The maternal and perinatal mortality rates are slightly higher in China than in Western countries. Unscarred CUR and non-CS-scarred CUR are associated with higher risks of adverse maternal and perinatal outcomes than CS-scarred CUR. Identification of the rupture type is helpful for clinical decision-making. Funding: CAMS initiative for Innovative Medicine (CAMS-12 M; 2017-12M-1-002) Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This study used only medical records data, and it was approved by the institutional review board of PUMCH.

I study the effect of mutual funds’ securities lending activities on their participation in proxy voting using hand-collected fund securities lending data. Consistent with Shleifer and Vishny’s (1986) argument that a shareholder’s willingness to monitor a firm decreases as the cost of monitoring increases, I find that mutual funds that lend securities are less likely to vote in the shareholder meetings of their portfolio firms. The negative effect is weaker if a fund holds a larger stake in the stock, especially poorly performing stocks, suggesting that lending funds are more likely to give up securities lending income and recall stocks to vote when the potential gains from voting are greater. This negative effect of securities lending on voting participation is also weaker if other funds in the same fund family are active voters. Although securities lending impedes fund voting on average, I find that it increases fund voting, due to a “lock-in” effect, in a subset of fund families in which funds are restricted from selling upon short-selling signals and vote more actively.

Background: Diagnosis of thyroid-stimulating hormone (TSH)-secreting pituitary adenomas (TSHoma) before surgery remains a challenge, especially microadenomas. We aimed to establish a short-term somatostatin analogues (SSA) test to differentiate TSHoma from resistance of thyroid hormone (RTH). Methods: We first evaluated the sensitivity and specificity of SSA test in a retrospective cohort (TSHoma, N=32; RTH, N=20). We then applied the SSA test in a perspective SITSH cohort without THRB gene mutation (pituitary microadenoma, N=10; negative pituitary imaging, N=7). Findings: In the retrospective cohort, both TSHoma and RTH patients showed a decrease of TSH at the start of the SSA test, but the velocity of TSH slowly decreased in RTH patients after 2 h. The suppression ratio of TSH at 24 h versus 2 h and 0 h in TSHoma patients was remarkably greater than in RTH patients. The 24 h versus 2 h suppression ratio showed the best diagnostic accuracy at a cut-point of 44·46%, with sensitivity as 95·00%, specificity as 93·75%. In the perspective cohort, 10/17 patients diagnosed as TSHoma with mean TSH suppression ratio of 68·91%, in which seven patients with microadenoma received pituitary surgery and achieved euthyroid with positive TSH staining in the resected tissues. Interestingly, two patients with negative pituitary imaging showed TSH suppression ratio greater than 44·46% and developed microadenomas at follow-up. Interpretation: A short-term SSA test provides an alternative diagnostic approach for TSHoma, especially microadenoma. It may also diagnose TSHoma in very early stage before positive findings in pituitary imaging. Funding Statement: This study was sponsored by the grants from National Science Foundation of China (81570702, 81400772, 81700686). Foundation of Health and Family planning Commission of Shanghai (20174Y0204). National International Science Cooperation Foundation (2015DFA30560). The National Key Research and Development Program of China (2016YFC0901503). Declaration of Interests: The authors state: "No conflicts of interest to declare." Ethics Approval Statement: The board of medical ethics of Ruijin Hospital approved the study, and all patients provided informed written consent.

It is recognized that the interaction between cells and their physical microenvironment plays a fundamental role in controlling cell behaviours and even in determining cell fate. Any change in the physical properties of the extracellular matrix (ECM), such as its topography, geometry or stiffness, controls this interaction. In the current study, we revealed a novel connection between the cell-matrix interaction and cell-cell communication that is mediated by interface stiffness, and elucidated this process in stem cells from human apical papilla (hSCAPs) in terms of mechanosensing, mechanotransduction and gap junction-mediated cell-cell communication. We first fabricated polydimethylsiloxane (PDMS) substrates with the same topography and geometry but different stiffnesses and found that the cell morphology of the hSCAPs actively changed to adapt to the difference in substrate stiffness, and we also found that the hSCAPs secreted more fibronectin in response to the stiff substrate. The focal adhesion plaques were changed by altering the expression of focal adhesion kinase (FAK) and paxillin. The FAK and paxillin bound to connexin 43 and, as a result, altered the gap junction formation. By a Lucifer yellow transfer assay, we further confirmed that the interface stiffness mediated cell-cell communication in living hSCAPs via changes in gap junction tunnels. The novel mechanics that mediated cell-cell communication through extracellular stiffness that was observed in this study show the great influence of the interaction between cells and their external physical microenvironment and stress the importance of microenvironmental mechanics in organ development and diseases.

This study selected fifth graders from D Primary School as subjects and conducted a 12-week mindfulness education experiment using a pre- and post-test control experiment design. The results can be used to demonstrate that mindfulness education has a significant impact on children’s attention development, emotional balance and development, psychological development and happiness enhancement. These aspects interact with each other to jointly improve the overall development level of children. Therefore, activities of mindfulness education are necessary and should be carried out moderately at school, thus giving full play to the positive role of mindfulness education in child development.

Biomechanics is a fundamental feature of a cell. The manner by which a mechanical feature could affect immune evasion of tumor cells remains an enigma. Here we show that although cytotoxic T lymphocytes (CTL) can effectively destroy stiff differentiated tumor cells, they fail to kill tumor-repopulating cells (TRC), whose softness effectively impedes the pore formation process through perforin released from CTLs. Mechanistically, perforin interacting with nonmuscle myosin heavy chain 9 transmits forces to fewer F-actins in soft TRCs, thus inducing a weak contractile force which is inadquate for pore formation by perforin. Stiffening soft TRCs confers perforin the drilling ability, leading to CTLs killing the TRCs, thus achieving a better tumor immunotherapeutic outcome. More importantly, overcoming the mechanical softness also enhances the killing of human TRCs by human CTLs. These findings provide mechanics-based immunotherapeutic strategies with potential clinical applications.

This paper offers a framework to understand informal financing based on mechanisms to deal with asymmetric information and enforcement. We find that constructive informal financing such as trade credits and family borrowing that relies on information advantages or an altruistic relationship is associated with good firm performance. Underground financing such as money lenders who use violence for enforcement is not. Constructive informal financing is prevalent in regions where access to bank loans is extensive, while its role in supporting firm growth decreases with bank loan availability. International comparisons show that China is not an outlier but rather average in using informal financing.

We survey the growing academic literature using Abel Noser data, including 55 publications thus far. We analyze publication patterns to explore how the availability of a specialized microstructure dataset propagates across different areas within finance and into other disciplines such as accounting. Of note, we identify corporate finance and accounting as the most under-researched areas that offer promising opportunities for future academic research using the data. To provide guidance for researchers interested in using Abel Noser data, we analyze institutional trading using transaction-level data spanning more than 12 years and covering 233 million transactions with $37 trillion traded. We provide background information on the origin and history of the data, offer suggestions for cleaning and using the data, and discuss (dis)advantages of Abel Noser compared to other data sources for institutional trading. We also document two simple facts: 1) institutional trade sizes decline dramatically over time, rendering trade size-based inferences of institutional trades problematic; 2) we estimate that Abel Noser data cover 12% of CRSP volume over our sample period and 15% for 1999–2005, significantly higher than the estimate in Puckett and Yan (2011) for 1999–2005: 8%, a widely quoted number in the literature. This background should prove useful for researchers seeking to address a number of as yet unexplored issues, especially in corporate finance and accounting research.

We examine the propagation of governance mechanisms across firms held by the same institutional activist blockholders (IABs). We find that a firm is more likely to adopt clawback provisions when more of other firms held by the same IABs have adopted clawback — an effect we call traveling governance. This effect is stronger when the level and duration of common ownership by IABs are higher, and when IABs have more past activism experiences. This traveling governance effect is distinct from peer-effects stemming from common industry, common location, or board interlocks. Our results are not driven by endogenous selection by IABs. Further, our placebo tests show that this traveling governance is absent for firms held by the same passive institutional blockholders and firms that share common IABs only in the past. Finally, we find that traveling governance substitutes internal board governance, but complements external governance by the product market. Overall, our findings suggest that IABs act as effective gatekeepers to monitor their portfolio firms through an indirect and potentially less costly mechanism.

We analyze the impact of the staggered adoption of state-level constituency statutes on corporate social responsibility (CSR), and the value implication of adjusting CSR engagement in response to the adoption of constituency statutes. The constituency statutes allow firms to consider interests of non-shareholder stakeholders and provide firms with discretion as to how stakeholder interests are considered. We find that firms respond to the adoption of constituency statutes by increasing CSR engagement. Besides, the positive impact of constituency statutes on CSR engagement is more pronounced for firms that distribute more cash to shareholders. In addition, we find that increased CSR engagement after the adoption of constituency statutes leads to increases in firm valuation, especially for firms that have a poorer information environment. This indicates that CSR engagement can mitigate the conflict between shareholders and stakeholders by promoting the interests of both parties. Taken together, our paper highlights the efficacy of stakeholder orientation in CSR and provides supporting evidence for the shareholder wealth maximization perspective of CSR.

We analyze the role of common equity blockholders in fostering the formation of strategic alliances, establish a positive causal effect of strategic alliances on corporate innovation, and analyze the channels through which strategic alliances foster innovation. Our findings may be summarized as follows. First, there is a positive relation between the fraction of a firm's industry peers with which it shares common blockholders and the number of strategic alliances that it enters into. Second, there is a positive relation between the RD and second, by using an instrumental variables approach. Fifth, we establish that an important channel through which strategic alliances foster greater innovation is through the more efficient redeployment of human capital (inventors) across alliance partners.

Stocks that initiate dividends tend to co-move more with other dividend paying stocks and co-move less with stocks that are non-dividend payers. These changes in return comovement do not come from variations in firm fundamentals or characteristics. Instead, comovement in stock returns and trading activities are related to investor preference for dividends. Mutual funds that prefer dividends hold more of the dividend initiators and flows to these funds move the prices of dividends payers in tandem. Our findings support a clientele-based explanation for return comovement, which becomes stronger following periods of high dividend sentiment.

I find that mutual funds that invest heavily in publicly traded family firms (pro-FF funds) outperform other funds. Trading by funds, which overweigh family firms, predicts family firms’ future stock returns and earnings announcement surprises. Consistent with an informed fund hypothesis, pro-FF funds’ outperformance is greater when family firms they hold are harder to value or less liquid. I find that pro-FF funds acquire an information advantage by investing in family firms located geographically closer to them. Mutual funds realizes a positive aggregate return on family firms. Overall, this study shows that investing in family firms benefits mutual funds.