Interplay of Drop Shedding Mechanisms on High Wettability Contrast Biphilic Stripe-Patterned Surfaces.

To improve the rate of DWC, numerous studies have adjusted the distribution of drops through biphilic surface patterning and wettability gradients to control the nucleation and drop shedding rates on the condensing surface, yet the connection between drop shedding mechanisms and surface wettability patterning remains unclear. Moreover, wettability patterning places geometric bounds on the governing forces (i.e., gravity, capillary, and inertia), which drive the droplet shedding mechanisms. Thus, the subsequent influence of droplet distribution along the DWC regions on the shedding mechanisms may not be known a priori. In this study, the area fraction, ADWC, of the DWC and also the DWC region width, LN, were varied between 10 and 50% and 0.5-1.5 mm, respectively, to probe the dominant droplet shedding mechanisms on a high wettability contrast surface (i.e., the contact angle on the DWC was 159 ± 3.4° and the hysteresis 9 ± 3.6°, whereas the FWC was nearly perfectly wetting). Humid air was introduced inside a custom-built chamber with the upright steady-state condensation imaged by both real-time and high-speed imaging techniques. We found that the droplet shedding mechanisms changed with increasing LN where the sliding drop radii are reduced with LN while the jumping drop radii remained unchanged with LN. The maximum drop size for shedding also decreased by 13%, which we attribute to the secondary droplet inertia, which helps gravity overcome the capillary retention force. Lastly, although many studies have probed DWC enhancements via surface wettability patterning, an optimal combination of ADWC and LN provided in this study significantly aids in the improvement of future DWC-based condensers and water collector applications.

[Puerarin alleviates lipopolysaccharide-induced acute kidney injury in mice by modulating the SIRT1/NF-κB pathway].

OBJECTIVE: To investigate the role of the SIRT1/NF-κB pathway in mediating the effect of puerarin against lipopolysaccharide (LPS)-induced acute kidney injury (AKI). METHODS: Fifteen BALB/C mice were randomized into control group, LPS group and puerarin treatment group, and in the latter two groups, the mice were given an intraperitoneal injection of LPS (5 mg/kg), followed by daily injection of normal saline for 3 days or injection of puerarin (25 mg/kg) given 1 h later and then on a daily basis for 3 days. On day 5 after modeling, the kidney tissues were taken for histological observation and detection of cell apoptosis. The renal function indexes including urea nitrogen (BUN), serum creatinine (Scr) and kidney injury molecule 1 (KIM-1) and the levels of tumor necrosis factor (TNF-α) and interleukin 1ß (IL-1ß) were measured, and the expressions of SIRT1 and NF-κB-p65(acetyl K310) in the renal tissues were detected. RESULTS: Intraperitoneal injection of LPS caused obvious glomerular capillary dilatation, hyperemia, renal interstitial edema, and renal tubular epithelial cell swelling and deformation in the mice. The mouse models of LPS-induced AKI also showed significantly increased renal tubular injury score and renal cell apoptosis (P < 0.01) with increased serum levels of BUN, Scr, KIM-1, TNF-α and IL-1ß (P < 0.01), enhanced renal expressions of TNF-α, IL-1ß and NF-κB p65(acetyl K310) (P < 0.01) and lowered renal expression of SIRT1 (P < 0.05). Treatment with puerarin effectively alleviated LPS-induced renal interstitial edema and renal tubular epithelial cell shedding, lowered renal tubular injury score (P < 0.01) and renal cell apoptosis rate (P < 0.01), and decreased serum levels of BUN, Scr, KIM, TNF-α and IL-1ß (P < 0.01). Puerarin treatment significantly reduced TNF-α, IL-1ß and NF-κB p65 (acetyl K310) expression in the renal tissue (P < 0.05) and increased SIRT1 expression by 17% (P < 0.05) in the mouse models. CONCLUSION: Puerarin can effectively alleviate LPS-induced AKI in mice possibly by modulating the SIRT1/NF-κB signaling pathway.

EFFECT OF ABDOMINAL IRRADIATION IN MICE MODEL OF INFLAMMATORY BOWEL DISEASE.

Inflammatory bowel diseases could be diagnosed in major measure by diagnostic imaging; however, radiation exposure in the intestine may also contribute to the progression of these pathologies. To better understand the impact of radiation in the presence of bowel disease, we administered dextran sodium sulfate (DSS) to C57BL/6 mice to induce colitis and exposed to radiation at abdominal area. We observed that abdominal irradiation (13 Gy) aggravates the DSS-induced decrease in survival rate (0%), body weight (74.54 ± 3.59%) and colon length (4.98 ± 0.14 cm). Additionally, abdominal irradiation markedly increased in colonic inflammation levels (3.16 ± 0.16) compared with that of DSS-induced sham mice. Furthermore, abdominal irradiation also increased the mRNA expression levels of inflammatory genes, such as cyclooxygenase-2 (13.10 folds), interleukin-6 (48.83 folds) and tumor necrosis factor-alpha (42.97 folds). We conclude that abdominal irradiation aggravates the detrimental effects of DSS-induced colitis in mice, which might be a useful guideline for inflammatory bowel disease patients.

Multicenter Phase II Clinical Trial of Gemcitabine and Cisplatin as Neoadjuvant Chemotherapy for Patients With High-Grade Upper Tract Urothelial Carcinoma.

PURPOSE: Neoadjuvant chemotherapy (NAC) has proven survival benefits for patients with invasive urothelial carcinoma of the bladder, yet its role for upper tract urothelial carcinoma (UTUC) remains undefined. We conducted a multicenter, single-arm, phase II trial of NAC with gemcitabine and split-dose cisplatin (GC) for patients with high-risk UTUC before extirpative surgery to evaluate response, survival, and tolerability. METHODS: Eligible patients with defined criteria for high-risk localized UTUC received four cycles of split-dose GC before surgical resection and lymph node dissection. The primary study end point was rate of pathologic response (defined as < ypT2N0). Secondary end points included progression-free survival (PFS), overall survival (OS), and safety and tolerability. RESULTS: Among 57 patients evaluated, 36 (63%) demonstrated pathologic response (95% CI, 49 to 76). A complete pathologic response (ypT0N0) was noted in 11 patients (19%). Fifty-one patients (89%) tolerated at least three complete cycles of split-dose GC, 27 patients (47%) tolerated four complete cycles, and all patients proceeded to surgery. With a median follow up of 3.1 years, 2- and 5-year PFS rates were 89% (95% CI, 81 to 98) and 72% (95% CI, 59 to 87), while 2- and 5-year OS rates were 93% (95% CI, 86 to 100) and 79% (95% CI, 67 to 94), respectively. Pathologic complete and partial responses were associated with improved PFS and OS compared with nonresponders (≥ ypT2N any; 2-year PFS 100% and 95% v 76%, P < .001; 2-year OS 100% and 100% v 80%, P < .001). CONCLUSION: NAC with split-dose GC for high-risk UTUC is a well-tolerated, effective therapy demonstrating evidence of pathologic response that is associated with favorable survival outcomes. Given that these survival outcomes are superior to historical series, these data support the use of NAC as a standard of care for high-risk UTUC, and split-dose GC is a viable option for NAC.

[Feasibility and effectiveness of application of internet-based HIV testing in men who have sex with men].

Objective: To evaluate the feasibility and effectiveness of the application of internet-based HIV testing in men who have sex with men (MSM) in practical application and provide evidence for its application in the future. Methods: MSM who visited the internet-based intervention platform for at least one time from June to December 2020 were selected for the study. The information about platform visit, the number of self-test kits provided, the basic characteristics of the MSM and their satisfactory level were collected. And multivariable logistic regression analyses were conducted to identify the potential factors associated with the reporting of self-test results. Results: By the end of December 31th, 2020, a total of 132 267 platform visits had been recorded, and 3 511 HIV self-test kits had been provided upon the MSM's requests, and 3 237 MSM (92.2%) reported self-test results. The HIV positive rate was 2.4% (69/2 855) and the confirmation rate of positive HIV test results was 86.7% (52/60). The MSM who asked for self-test kits online were mainly aged ≤30 years, had education level of college or above, and found their sexual partners through internet or dating software. Multivariable logistic regression analyses showed that repeat of online HIV self-test kits application (OR=3.50,95%CI:2.10-5.83), guarantee deposit of 50 yuan at application (OR=2.55,95%CI:1.33-4.89), monthly economic income 1-3 000 yuan (OR=1.54,95%CI:1.05-2.28) or no income (OR=1.71,95%CI:1.20-2.42) and online sexual partners finding (OR=1.49,95%CI:1.13-1.95) were associated with higher reporting rate of self-test results. The satisfactory rate the MSM to the service of platform was 99.5% (217/218). Conclusions: The study confirmed the feasibility and effectiveness of internet-based intervention for HIV tests in MSM, which could promote the self-test of HIV in MSM and facilitate the early detection of HIV infection through social media platforms and multi-channel promotion.

Conserved features of TERT promoter duplications reveal an activation mechanism that mimics hotspot mutations in cancer.

Mutations in the TERT promoter represent the genetic underpinnings of tumor cell immortality. Beyond the two most common point mutations, which selectively recruit the ETS factor GABP to activate TERT, the significance of other variants is unknown. In seven cancer types, we identify duplications of wildtype sequence within the core promoter region of TERT that have strikingly similar features including an ETS motif, the duplication length and insertion site. The duplications recruit a GABP tetramer by virtue of the native ETS motif and its precisely spaced duplicated counterpart, activate the promoter and are clonal in a TERT expressing multifocal glioblastoma. We conclude that recurrent TERT promoter duplications are functionally and mechanistically equivalent to the hotspot mutations that confer tumor cell immortality. The shared mechanism of these divergent somatic genetic alterations suggests a strong selective pressure for recruitment of the GABP tetramer to activate TERT.

Convolutional neural network-aided tuber segmentation in tuberous sclerosis complex patients correlates with electroencephalogram.

OBJECTIVE: One of the clinical hallmarks of tuberous sclerosis complex (TSC) is radiologically identified cortical tubers, which are present in most patients. Intractable epilepsy may require surgery, often involving invasive diagnostic procedures such as intracranial electroencephalography (EEG). Identifying the location of the dominant tuber responsible for generating epileptic activities is a critical issue. However, the link between cortical tubers and epileptogenesis is poorly understood. Given this, we hypothesized that tuber voxel intensity may be an indicator of the dominant epileptogenic tuber. Also, via tuber segmentation based on deep learning, we explored whether an automatic quantification of the tuber burden is feasible. METHODS: We annotated tubers from structural magnetic resonance images across 29 TSC subjects, summarized tuber statistics in eight brain lobes, and determined suspected epileptogenic lobes from the same group using EEG monitoring data. Then, logistic regression analyses were performed to demonstrate the linkage between the statistics of cortical tuber and the epileptogenic zones. Furthermore, we tested the ability of a neural network to identify and quantify tuber burden. RESULTS: Logistic regression analyses showed that the volume and count of tubers per lobe, not the mean or variance of tuber voxel intensity, were positively correlated with electrophysiological data. In 47.6% of subjects, the lobe with the largest tuber volume concurred with the epileptic brain activity. A neural network model on the test dataset showed a sensitivity of .83 for localizing individual tubers. The predicted masks from the model correlated highly with the neurologist labels, and thus may be a useful tool for determining tuber burden and searching for the epileptogenic zone. SIGNIFICANCE: We have proven the feasibility of an automatic segmentation of tubers and a derivation of tuber burden across brain lobes. Our method may provide crucial insights regarding the treatment and outcome of TSC patients.

Oscillation Dynamics of Drops on Immiscible Thin Liquid Films.

While drop oscillation dynamics has been widely studied for many decades, the influence of a moving contact line on the oscillation modes of drops remains underexplored. Herein, we report the oscillation dynamics of drops on thin liquid films with different viscosities where lower viscosities provide a slipping surface and higher viscosities immobilize the contact line. A gently deposited drop onto an oil film undergoes shape oscillations due to capillarity, where the frequency, amplitude, and apparent contact angle are tracked via a high-speed camera. This study demonstrates that restraining the mobility of the drop contact line by increasing the viscosity of a thin oil film underneath the drop increases the extent of the drop oscillation time as well as affecting the natural frequency of the drop oscillation. The drop oscillation time was defined by the time at which the changes in the drop height dropped to values less than 1% of the equilibrium height. The experimental results for the first longitudinal mode oscillation frequencies as a function of the equilibrium contact angles for the pinning and slipping contact lines were in good agreement with previously reported numerical simulations and model predictions.

Development and validation of an individualized nomogram for predicting the high-volume (> 5) central lymph node metastasis in papillary thyroid microcarcinoma.

PURPOSE: Papillary thyroid microcarcinoma (PTMC) frequently presents a favorable clinical outcome, while aggressive invasiveness can also be found in some of this population. Identifying the risk clinical factors of high-volume (> 5) central lymph node metastasis (CLNM) in PTMC patients could help oncologists make a better-individualized clinical decision. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the Surveillance, Epidemiology, and End Results (SEER) database between Jan 2010 and Dec 2015 and in one medical center affiliated to Chongqing Medical University between Jan 2018 and Oct 2020. Univariate and multivariate logistic regression analyses were used to determine the risk factors for high volume of CLNM in PTMC patients. RESULTS: The male gender (OR = 2.02, 95% CI 1.46-2.81), larger tumor size (> 5 mm, OR = 1.64, 95% CI 1.13-2.38), multifocality (OR = 1.87, 95% CI 1.40-2.51), and extrathyroidal invasion (OR = 3.67; 95% CI 2.64-5.10) were independent risk factors in promoting high-volume of CLNM in PTMC patients. By contrast, elderly age (≥ 55 years) at diagnosis (OR = 0.57, 95% CI 0.40-0.81) and PTMC-follicular variate (OR = 0.60, 95% CI 0.42-0.87) were determined as the protective factors. Based on these indicators, a nomogram was further constructed with a good concordance index (C-index) of 0.702, supported by an external validating cohort with a promising C-index of 0.811. CONCLUSION: A nomogram was successfully established and validated with six clinical indicators. This model could help surgeons to make a better-individualized clinical decision on the management of PTMC patients, especially in terms of whether prophylactic central lymph node dissection and postoperative radiotherapy should be warranted.

The role of stereo-electroencephalography to localize the epileptogenic zone in children with nonlesional brain magnetic resonance imaging.

OBJECTIVE: This study aimed to assess the clinical outcome and outcome predictive factors in pediatric epilepsy patients evaluated with stereo-electroencephalography (SEEG). METHODS: Thirty-eight patients who underwent SEEG implantation at the Pediatric Epilepsy Center in New York Presbyterian Hospital between June 2014 and December 2019 were enrolled for retrospective chart review. Postoperative seizure outcomes were evaluated in patients with at least 12-months follow up. Meta-analysis was conducted via electronic literature search of data reported from 2000 to 2020 to evaluate significant surgical outcome predictors for SEEG evaluation in the pediatric population. RESULTS: In the current case series of 25 postsurgical patients with long-term follow up, 16 patients (64.0%) were seizure free. An additional 7 patients (28.0%) showed significant seizure improvement and 2 patients (8.0%) showed no change in seizure activity. Patients with nonlesional magnetic resonance imaging (MRI) achieved seizure freedom in 50% (5/10) of cases. By comparison, 73% (11/15) of patients with lesional MRI achieved seizure freedom. Out of 12 studies, 158 pediatric patients were identified for inclusion in a meta-analysis of the effectiveness of SEEG. Seizure freedom was reported 54.4% (n = 86/158) of patients at last follow up. Among patients with nonlesional MRI, 45% (n = 24) achieved seizure freedom compared with patients with lesional MRI findings (61.2%, n:= 60) (p = 0.02). The risk for seizure recurrence was 2.15 times higher [95% confidence interval [CI] 1.06-4.37, p = 0.033] in patients diagnosed with nonlesional focal epilepsy compared to those with lesional epilepsy [ 1.49 (95% CI 1.06-2.114, p = 0.021]. CONCLUSION: Evaluation by SEEG implantation in pediatric epilepsy is effective in localizing the epileptogenic zone with favorable outcome. Presence of a non-lesional brain MRI was associated with lower chances of seizure freedom. Further research is warranted to improve the efficacy of SEEG in localizing the epileptogenic zone in pediatric patients with non-lesional brain MRI.

Drop Bouncing Dynamics on Ultrathin Films.

For drops to contact various surfaces, the removal of the interstitial fluid is the prerequisite to contact. While the conventional understanding is for drops to irreversibly spread on a film made of the same substance, we describe the dynamics of drops initiating contact yet carrying enough momentum to completely lift off of the substrate which we label as contact bouncing. We report new experimental results of the dynamics between drops impacting thin films described by the ratio of the liquid film hL to the drop with diameter D0 for the range of 0.004 < hL/D0 < 0.08. Using high-speed interferometry, we visualize the interfacial gas layer spatiotemporal signatures across the various film thicknesses and Weber numbers. We find that while increasing the deformability of the thin films enhances the gas entrainment phenomenon at early times, it also increases the rate of the gas purging rate, increasing the chance of contact just prior to the gas film retraction and drop lift off sequence. Drops which contact the liquid film during the retraction stage are able to bounce with <5% volume loss.

Fracture recurrence in hip fracture with menopausal hormone therapy versus risedronate: a clinical trial.

OBJECTIVES: An open-label, randomized trial was conducted to examine the effects of risedronate versus menopausal hormone therapy (MHT) in postmenopausal women with recent hip fracture. METHODS: Among 1165 eligible women, 281 were recruited and randomly assigned to receive oral risedronate (35 mg/week) or percutaneous estradiol gel (1.5 mg/day) plus oral micronized progesterone (100 mg/day) for 4 years. The primary end point was recurrent fracture and the secondary end points were mortality and bone mineral density (BMD). RESULTS: Kaplan-Meier analyses showed no significant differences in fracture recurrence and mortality between the two groups. The incidence of any new fracture per 100 person-years (PY) was 8.63 in the risedronate group and 12.86 in the MHT group (p = 0.180); that of clinical fracture was 4.75 and 6.99, respectively (p = 0.265); and that of asymptomatic vertebral fracture was 4.87 and 5.58, respectively (p = 0.764). The respective incidence of death per 100 PY was 3.58 and 4.40 (p = 0.503). BMD increased comparably at the lumbar spine in both groups. BMD at the total hip did not change in the risedronate group, but increased significantly by 2.8% in the MHT group. CONCLUSIONS: MHT might not differ from risedronate in the prevention of secondary fractures and death among postmenopausal women with recent hip fracture.

Construction and validation of a nomogram for predicting cervical lymph node metastasis in classic papillary thyroid carcinoma.

PURPOSE: Patients with papillary thyroid carcinoma (PTC) frequently present a relatively poor prognosis when they coexist with cervical lymph node metastasis (LNM). Moreover, it remains controversial whether prophylactic lymph node dissection (LND) should be performed for patients without clinically lymph node metastasis. Thus, we hereby develop a nomogram for predicting the cervical LNM (including central and lateral LNM) in patients with PTC. METHODS: We retrospectively reviewed the clinical characteristics of adult patients with PTC in the surveillance, epidemiology, and end results (SEER) database between 2010 and 2015 and in our Department of Breast and Thyroid Surgery in the Second Affiliated Hospital of Chongqing Medical University between 2019 and 2020. RESULT: A total of 21,972 patients in the SEER database and 747 patients in our department who met the inclusion criteria were enrolled in this study. Ultimately, six clinical features including age, gender, race, extrathyroidal invasion, multifocality, and tumor size were identified to be associated with cervical LNM in patients with PTC, which were screened to develop a nomogram. This model had satisfied discrimination with a concordance index (C-index) of 0.733, supported by both internal and external validation with a C-index of 0.731 and 0.716, respectively. A decision curve analysis was subsequently made to evaluate the feasibility of this nomogram for predicting cervical LNM. Besides, a positive correlation between nomogram score and the average number of lymph node metastases was observed in all groups. CONCLUSION: This visualized multipopulational-based nomogram model was successfully established. We determined that various clinical characteristics were significantly associated with cervical LNM, which would be better helping clinicians make individualized clinical decisions for PTC patients.

Sequencing of PD-1/L1 Inhibitors and Carboplatin Based Chemotherapy for Cisplatin Ineligible Metastatic Urothelial Carcinoma.

PURPOSE: Current first line treatment options in patients with metastatic urothelial carcinoma unfit to receive cisplatin containing chemotherapy include PD-1/L1 inhibitors and carboplatin containing chemotherapy. However, the optimal sequencing of these therapies remains unclear. MATERIALS AND METHODS: We conducted a multicenter retrospective analysis. Consecutive cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line carboplatin containing chemotherapy followed sequentially by second line PD-1/L1 inhibitor, or the reverse order, were included. Patient demographics, objective response, time to treatment failure for first line and second line therapy, interval between end of first line and initiation of second line treatment (Interval1L-2L) and overall survival were collected. Multivariate analysis was conducted to examine the association of sequencing on overall survival. RESULTS: In this multicenter retrospective study we identified 146 cisplatin ineligible patients with metastatic urothelial carcinoma treated with first line PD-1/L1 inhibitor therapy followed by second line carboplatin containing chemotherapy (group 1, 43) or the reverse sequence (group 2, 103). In the overall cohort median age was 72, 76% were men and 18% had liver metastasis. In both groups objective response rates were higher with carboplatin containing chemotherapy (45.6% first line, 44.2% second line) compared to PD-1/L1 inhibitors (9.3% first line, 21.3% second line). On multivariate analysis treatment sequence was not associated with overall survival (HR 1.05, p=0.85). Site of metastasis was the only factor significantly associated with overall survival (p=0.002). CONCLUSIONS: In this biomarker unselected cohort of cisplatin ineligible patients with metastatic urothelial carcinoma, PD-1/L1 inhibitor followed by carboplatin containing chemotherapy and the reverse sequence had comparable overall survival.

The effect of myocardial injury on the clinical course of snake envenomation in South Korea.

CONTENT: This study investigated the incidence, progression and clinical course of myocardial injury-related snake envenomation in South Korea. In addition, this study evaluated whether antivenom guidelines are appropriate to control envenomation in patients with myocardial injury. METHODS: The study included 198 patients who received antivenom after a snakebite, and they were divided into two groups according to evidence of myocardial injury (defined as elevated troponin I or ischemic change on electrocardiogram) at presentation. Data including serial troponin I, echocardiogram/coronary angiogram findings, the clinical course, and treatment were collected and analyzed. RESULTS: The incidence of myocardial injury at presentation was 15.2%. The troponin I level was 0.11 (0.07-0.56) ng/ml at presentation and tended to decrease over 24 h. Echocardiograms revealed neither regional wall motion abnormalities nor left ventricular dysfunction in 15 of 17 patients, while two patients showed signs of coronary artery stenosis on echocardiograms and coronary angiograms. However, compared with patients without myocardial injury, patients with myocardial injury had a higher frequency of systemic envenomation complications, including bleeding, respiratory failure, hypotension, acute kidney injury, thrombocytopenia and venom-induced consumption coagulopathy (VICC). The patients with myocardial injury at presentation needed significantly more frequent and larger doses of antivenom than indicated by the initial severity of envenomation. Multivariate analysis showed that myocardial injury was associated with the need for additional antivenom administration after initial administration. DISCUSSION AND CONCLUSION: Myocardial injury is not uncommon after snake envenomation in Korea. Although myocardial injury itself seems to be benign, the clinical course of patients with myocardial injury is complicated, and myocardial injury is associated with the need for additional antivenom administration. The optimal use of antivenom to control envenomation in patents with myocardial injury after snake envenomation in South Korea should be established.

[Study on chemical constituents from Euphorbia thymifolia].

This work was launched to study on the chemical constituents from Euphorbia thymifolia. Thirteen compounds were isolated from the 95% ethanol extract of the aerial parts of E. thymifolia by column chromatographies on silica gel, Sephadex LH-20, MCI, and ODS, and preparative HPLC, including two thymol derivatives(1-2), four alkaloids(3-6), five isocoumarins(7-11), together with two ellagic acids(12-13). All the compounds are listed as follows:(Z)-8,9-dehydro-9,10-diisobutyryloxythymol(1), 8-hydro-xy-9,10-diisobutyryloxythymol(2), N-(N-benzoyl-L-phenylalanyl)-L-phenylalanol(3), aurantiamide acetate(4), 1-carboethoxy-ß-carboline(5), isoechinulin A(6), ethyl brevifolincarboxylate(7), euphorhirtin B(8), 4,5-didehydro chebulic acid triethyl ester(9), euphorhirtin G(10), pomegranatate(11), 3,3',4'-tri-O-methylellagic acid(12), 3,3'-di-O-methylellagic acid(13). Compound 1 is a new compound. Except for compound 4, the others were isolated from this plant for the first time. All the compounds were screened for anti-neuroinflammatory activity in vitro, and compounds 1-3 and 7 showed significant activity with IC_(50) values of 0.19,12.93,7.29,25.4 µmol·L~(-1).

Locking Plates versus Locking Intramedullary Nails Fixation of Proximal Humeral Fractures Involving the Humeral Shaft: A Retrospective Cohort Study.

BACKGROUND For proximal humeral fractures (PHFs), locking intramedullary nails and locking plates have been widely used. However, few reports have been published on the therapy of complex PHFs accompanying humeral shaft fractures. Therefore, we performed this research to analyze the effectiveness of locking intramedullary nails and locking plates in the management of proximal humeral fractures involving the humeral shaft. MATERIAL AND METHODS We retrospectively reviewed 40 cases diagnosed with proximal humeral fractures involving the humeral shaft fixed with either locking intramedullary nails or locking plates with at least of 2 years' follow-up. Clinical data were obtained from the medical records. Follow-up data included the Constant-Murley score, American Shoulder and Elbow Surgeons score (ASES), visual analog scale score (VAS), and the relative strength of the supraspinatus and deltoid muscles. RESULTS In total, 19 locking plate patients and 21 locking intramedullary nail patients were analyzed. The average follow-up period was 35 months in the locking plate group and 34 months in the locking intramedullary nail group. There were obvious differences in the intraoperative blood loss, time of operation, and the length of operative incision between the 2 groups (p<0.05). There were no significant differences between the groups in Constant-Murley score, ASES, VAS, or the relative strength of supraspinatus and deltoid muscles. CONCLUSIONS For PHFs involving the humeral shaft, both locking plates and locking intramedullary nails can achieve satisfactory functional results in the long-term follow-up assessment. The locking intramedullary nail group was superior with regards to intraoperative blood loss, time of operation, and length of incision.

4D printing of self-folding and cell-encapsulating 3D microstructures as scaffolds for tissue-engineering applications.

Technology of tissue-engineering advanced rapidly in the last decade and motivated numerous studies in cell-engineering and biofabrication. Three-dimensional (3D) tissue-engineering scaffolds play a critical role in this field, as the scaffolds provide the biomimetic microenvironments that could stimulate desired cell behaviors for regeneration. However, despite many achievements, the fabrication of 3D scaffold remains challenging due to the difficulty of encapsulating cells in 3D scaffolds, controlling cell-cell organization in 3D, and being adapted by users unfamiliar with 3D biofabrication. In this study, we circumvent these obstacles by creating a four-dimensional (4D) inkjet-printing platform. This platform produces micropatterns that self-fold into a 3D scaffold. Seeding live cells uniformly onto the micropatterns before self-folding leads to cell-encapsulating 3D scaffolds with layer-wise cell-cell organization. Photo-crosslinkable biomaterial-inks of distinct swelling rates were synthesized from gelatin, and the biomaterial-inks were patterned by a customized high-precision inkjet-printer into bilayer micropatterns that were capable of self-folding into 3D microstructures. A mathematical model was developed to help design self-folding and to aid the understanding of the self-folding mechanism. Human umbilical vein endothelial cells (HUVECs) were embedded in self-folded microtubes to mimic microvessels. HUVECs in the microtube spread, proliferated, showed high cell viability, and engrafted on the microtube's inner wall mimicking the native endothelial cells. For physician and biologist end-users, this 4D printing method provides an easy-to-use platform that supports standard two-dimensional cell-seeding protocol while enabling the users to customize 3D cellularized scaffold as desired. This work demonstrated 4D printing as a promising tool for tissue-engineering applications.

Pharmaceutical-Grade Rigosertib Is a Microtubule-Destabilizing Agent.

We recently used CRISPRi/a-based chemical-genetic screens and cell biological, biochemical, and structural assays to determine that rigosertib, an anti-cancer agent in phase III clinical trials, kills cancer cells by destabilizing microtubules. Reddy and co-workers (Baker et al., 2020, this issue of Molecular Cell) suggest that a contaminating degradation product in commercial formulations of rigosertib is responsible for the microtubule-destabilizing activity. Here, we demonstrate that cells treated with pharmaceutical-grade rigosertib (>99.9% purity) or commercially obtained rigosertib have qualitatively indistinguishable phenotypes across multiple assays. The two formulations have indistinguishable chemical-genetic interactions with genes that modulate microtubule stability, both destabilize microtubules in cells and in vitro, and expression of a rationally designed tubulin mutant with a mutation in the rigosertib binding site (L240F TUBB) allows cells to proliferate in the presence of either formulation. Importantly, the specificity of the L240F TUBB mutant for microtubule-destabilizing agents has been confirmed independently. Thus, rigosertib kills cancer cells by destabilizing microtubules, in agreement with our original findings.

Renoprotective Effect of a Dipeptidyl Peptidase-4 Inhibitor on Aging Mice.

Dipeptidyl peptidase 4 (DPP-4) inhibitors exert pleiotropic effects beyond glycemic control. We investigated the renoprotective effects of DPP-4 inhibitors on aging mice mediated by the renin-angiotensin system (RAS). C57BL/6 mice were divided into three groups: the two-month-old mice (YM group), the eighteen-month-old mice (AM group) and the eighteen-month-old, linagliptin-treated mice (AM + LIN group). Renal function was improved, based on serum creatinine and cystatin-C levels (p < 0.05 compared with the AM group for both parameters). Fibrotic areas and the levels of proteins related to fibrosis improved in the AM + LIN group (p < 0.001 compared with the AM group for all parameters). In the AM + LIN group, the DPP-4-positive area and activity and expressions of DPP-4 were decreased (p < 0.05 compared with the AM group for all parameters). The levels of proteins related to the RAS, including prorenin receptor, angiotensin-converting enzyme, angiotensin II and angiotensin 1 receptor, were decreased in the AM + LIN group (p < 0.05, p < 0.01, p < 0.05, and p < 0.01 compared with the AM group, respectively). NADPH oxidase 2 and NADPH oxidase 4 levels decreased in the AM + LIN group (p < 0.001 compared with the AM group for both proteins), whereas the levels of endothelial nitric oxide synthase (eNOS) phosphorylated at serine1177 and superoxide dismutase 1 were increased (p < 0.01 compared with the AM group for both proteins). DPP-4 inhibitors may exert renoprotective effects via prorenin receptor/angiotensin-converting enzyme/angiotensin II/angiotensin 1 receptor axis.