Conformational Dynamics of Insulin

We have exploited a prandial insulin analog to elucidate the underlying structure and dynamics of insulin as a monomer in solution. A model was provided by insulin lispro (the active component of Humalog®; Eli Lilly and Co.). Whereas NMR-based modeling recapitulated structural relationships of insulin crystals (T-state protomers), dynamic anomalies were revealed by amide-proton exchange kinetics in D2O. Surprisingly, the majority of hydrogen bonds observed in crystal structures are only transiently maintained in solution, including key T-state-specific inter-chain contacts. Long-lived hydrogen bonds (as defined by global exchange kinetics) exist only at a subset of four α-helical sites (two per chain) flanking an internal disulfide bridge (cystine A20–B19); these sites map within the proposed folding nucleus of proinsulin. The anomalous flexibility of insulin otherwise spans its active surface and may facilitate receptor binding. Because conformational fluctuations promote the degradation of pharmaceutical formulations, we envisage that “dynamic re-engineering” of insulin may enable design of ultra-stable formulations for humanitarian use in the developing world

3-D calibration method and algorithm for freehand image of phased array ultrasonic testing

Phased array ultrasonic testing (UT) is an advanced technique applying ultrasound wave vibration theory to detect the flaw in tested materials by imaging. In this research, computer 3-D visualization of the flaw through calibrating the ultrasonic phased array image is proposed. 3-D calibration for ultrasonic phased array image is a procedure to calculate the spatial transformation matrix, spatial relationship between the US image plane and the tracker attached to the UT probe. The calibration method depends on a cross-string phantom and the corresponding algorithm. The phantom with a set of crosses guiding the operator quickly to find the scanning plane. The ten string crosses in the scanning plane provide the coordinates and spatial vectors for the calibration algorithm, thus the calibration algorithm can be realized based on the least-squares fitting method of the homologous points matching. Select the points having different distances and angles with the reference point to calculate the matrix and average them as the final result. The results show that the scanning plane positioning time is no more than 5 s. The precision and the accuracy results are the same as that is obtained through the other published methods in the medical 3-D ultrasound image calibration. The results make the 3-D flaw model reconstruction possible in phased array ultrasonic NDT. It will reduce the difficulties in the flaw recognizing and localization

The Gap Seal's Influences on the Leakage and Clamping of Multi-way Directional Valves

Defects coming from processing and assembly inevitably bring geometric and concentricity error to the fitting gap between valve core and frame. To overcome this problem, grooving was proven to be the most simple and effective method to reduce the hydraulic clamping force, and widely used on cylinder valve cores. Theoretically unbalanced forces kept going smaller with the increase of pressure equalizing grooves. When groove width increased, linearly the gap leakage extended. When the width was relatively small leakage was gradually reduced when depth increased. When the width was 1 mm, 1.5 mm or 2 mm, and the depth to width ratio was less than 1, leakage got worse with the increment of depth

Eastern Cooperative Oncology Group, β2-microglobulin, hemoglobin, and lactate dehydrogenase can predict early grade ≥ 3 infection in patients with newly diagnosed multiple myeloma: A real-world multicenter study

IntroductionThis research explored the clinical application of grade ≥ 3 infection predictive models for the newly diagnosed multiple myeloma (NDMM) population.MethodsIt evaluated 306 patients with NDMM based on three different predictive models. The relationship between the grade ≥ 3 infection rates in NDMM and the scores was analyzed retrospectively. The cumulative incidence of early grade ≥ 3 infection was estimated using the Kaplan–Meier method and log-rank test to assess the statistical significance of the difference. To compare the predictive performance in the prediction of infection, the Receiver Operating Characteristic Curve (ROC) curve was used to show the area under the curve (AUC), and DeLong’s test was used to analyze the difference in AUC.ResultsThe incidence of grade ≥ 3 infection within the first 4 months of NDMM was 40.20%. Concerning the FIRST score (predictors: ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase), GEM-PETHEMA score (predictors: albumin, male sex, ECOG, and non-IgA type MM), and Infection Risk model of Multiple Myeloma (IRMM) score (predictors: ECOG, serum β2-microglobulin, globulin, and hemoglobin), the probability of early grade ≥ 3 infection in the different groups showed statistically significant differences (low-risk vs. high-risk: 25.81% vs. 50.00%, p < 0.001; low-risk vs. moderate-risk vs. high-risk: 35.93% vs. 41.28% vs. 60.00%, p= 0.045; low-risk vs. moderate-risk vs. high-risk: 20.00% vs. 43.75% vs. 52.04%, p < 0.001). Statistical differences existed in the probability of early grade ≥ 3 infection among the different groups by the FIRST and IRMM scores but no statistical differences in the GEM-PETHEMA score (p < 0.001, p< 0.001, and p = 0.090, respectively). The FIRST score showed good discrimination and simple calculation with highest AUC. Further subgroup analysis showed that the FIRST score could still apply for patients treated with bortezomib-based regimen and frail patients.DiscussionOur findings indicate that the FIRST score (consisting of ECOG, β2-microglobulin, hemoglobin, and lactate dehydrogenase) is a simple and robust infection stratification tool for patients with NDMM and could be used in routine clinical work

Strategies for intraoperative management of the trigeminal nerve and long-term follow-up outcomes in patients with trigeminal neuralgia secondary to an intracranial epidermoid cyst

BackgroundEpidermoid cysts (ECs) are one of the most common causes of secondary trigeminal neuralgia (TGN). However, most previous studies have primarily focused on whether complete tumor resection was achieved, and few studies have discussed the primary goal of pain relief.ObjectiveThe present study provides intraoperative strategies for trigeminal nerve (TN) management in patients with TGN secondary to an EC and observed long-term follow-up outcomes.MethodsA total of 69 patients with TGN secondary to an EC at our hospitals were included (January 2011–June 2021). The same surgical team performed all surgeries using a retrosigmoid approach. After EC removal, different methods for TN management were used, including microvascular decompression (MVD), sharp capsulectomy, nerve combing and embedded cholesterol crystal excision. The epidemiological, clinical, and surgical data were extracted.ResultsThe total EC removal rate was 92.8% (64/69). All patients achieved initial pain relief postoperatively, and 12 patients (17.4%) experienced varying degrees of hemifacial hypesthesia, which was relieved within 3–6 months. Three patients (4.3%) reported partial pain recurrence within a median follow-up period of 5.5 (0.5–10.5) years, which was relieved completely after low-dose carbamazepine administration.ConclusionThe primary goal of surgical tumor removal for patients with TGN secondary to an EC is relief of the main symptom of tormenting pain. The selection of an appropriate strategy for TN, including MVD, sharp capsulectomy, nerve combing or embedded cholesterol crystal excision, should depend on the patient's situation

Rare earth elements in oysters and mussels collected from the Chinese coast: Bioaccumulation and human health risks

Rare earth elements (REEs) are increasingly used in various industries worldwide, resulting in their release into aquatic ecosystems. We evaluated the distribution and bioaccumulation of 14 REEs in marine sediments and biotas along the Chinese coasts. The total concentration of REEs (ΣREEs) in sediments was 41.65-170.94 mg/kg. The concentrations of ΣREEs were 1.97-4.77 and 0.62-4.96 mg/kg dry mass (DM) for oysters and mussels. The concentration of total light REEs (ΣLREEs) was higher than the concentration of total heavy REEs (ΣHREEs) at all samples. The bioaccumulation factor (BAF) of ΣLREEs was higher than ΣHREEs and BAF of ΣREE was 0.34-1.49 and 0.25-1.10 for oysters and mussels. The positive correlation between sediments and biotas was higher in mussels than oysters, showing a good potential for being environmental indicators for REEs. The risk of REEs to humans via oysters and mussels consumption could be negligible based on the estimated daily intake

PMMA/PDMS valves and pumps for disposable microfluidics

Poly(methyl methacrylate) (PMMA) is gaining in popularity in microfluidic devices because of its low cost, excellent optical transparency, attractive mechanical/chemical properties, and simple fabrication procedures. It has been used to fabricate micromixers, PCR reactors, CE and many other microdevices. Here we present the design, fabrication, characterization and application of pneumatic microvalves and micropumps based on PMMA. Valves and pumps are fabricated by sandwiching a PDMS membrane between PMMA fluidic channel and manifold wafers. Valve closing or opening can be controlled by adjusting the pressure in a displacement chamber on the pneumatic layer via a computer regulated solenoid. The valve provides up to 15.4 mu L s(-1) at 60 kPa fluid pressure and seals reliably against forward fluid pressure as high as 60 kPa. A PMMA diaphragm pump can be assembled by simply connecting three valves in series. By varying valve volume or opening time, pumping rates ranging from nL to mL per second can be accurately achieved. The PMMA based valves and pumps were further tested in a disposable automatic nucleic acid extraction microchip to extract DNA from human whole blood. The DNA extraction efficiency was about 25% and the 260 nm/280 nm UV absorption ratio for extracted DNA was 1.72. Because of its advantages of inexpensive, facile fabrication, robust and easy integration, the PMMA valve and pump will find their wide application for fluidic manipulation in portable and disposable microfluidic devices.NSFC [20805038, 20620130427]; MOE [200803841013]; 973 Program of China [2007CB935603, 2010CB732402]; XMU ; NIH [P01 CA077664