Hexagonal-Ge Nanostructures with Direct-Bandgap Emissions in a Si-Based Light-Emitting Metasurface.

Si-based emitters have been of great interest as an ideal light source for monolithic optical-electronic integrated circuits (MOEICs) on Si substrates. However, the general Si-based material is a diamond structure of cubic lattice with an indirect band gap, which cannot emit light efficiently. Here, hexagonal-Ge (H-Ge) nanostructures within a light-emitting metasurface consisting of a cubic-SiGe nanodisk array are reported. The H-Ge nanostructure is naturally formed within the cubic-Ge epitaxially grown on Si (001) substrates due to the strain-induced nanoscale crystal structure transformation assisted by far-from-equilibrium growth conditions. The direct-bandgap features of H-Ge nanostructures are observed and discussed, including a rather strong and linearly power-dependent photoluminescence (PL) peak around 1562 nm at room temperature and temperature-insensitive PL spectrum near room temperature. Given the direct-bandgap nature, the heterostructure of H-Ge/C-Ge, and the compatibility with the sophisticated Si technology, the H-Ge nanostructure has great potential for innovative light sources and other functional devices, particularly in Si-based MOEICs.

Lipid Tales: Optimizing Arylomycin Membrane Anchors.

Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts, no new antibiotic class with activity against Gram-negative bacteria has been approved in over 50 years. LepB inhibitors (LepBi) based on the arylomycin class of natural products are a novel class of antibiotics and function by inhibiting the bacterial type I signal peptidase (SPase) in Gram-negative bacteria. One critical aspect of LepBi development involves optimization of the membrane-anchored lipophilic portion of the molecule. We therefore developed an approach that assesses the effect of this portion on the complicated equilibria of plasma protein binding, crossing the outer membrane of Gram-negative bacteria and anchoring in the bacterial inner membrane to facilitate SPase binding. Our findings provide important insights into the development of antibacterial agents where the target is associated with the inner membrane of Gram-negative bacteria.

Congenital diaphragmatic hernia.

A fetus was found to have a right diaphragmatic hernia during a prenatal ultrasonography examination late in the second trimester. A "green channel" with multi department dynamic monitoring was instituted, at 40 + 4 weeks, with the infant under general anesthesia, hernia repair was later successfully performed. After the operation, the infant's vital signs were stable and their condition remained good during follow-up.

Building Machine Learning Small Molecule Melting Points and Solubility Models Using CCDC Melting Points Dataset.

Predicting solubility of small molecules is a very difficult undertaking due to the lack of reliable and consistent experimental solubility data. It is well known that for a molecule in a crystal lattice to be dissolved, it must, first, dissociate from the lattice and then, second, be solvated. The melting point of a compound is proportional to the lattice energy, and the octanol-water partition coefficient (log P) is a measure of the compound's solvation efficiency. The CCDC's melting point dataset of almost one hundred thousand compounds was utilized to create widely applicable machine learning models of small molecule melting points. Using the general solubility equation, the aqueous thermodynamic solubilities of the same compounds can be predicted. The global model could be easily localized by adding additional melting point measurements for a chemical series of interest.

High-efficiency Ge-based waveguide photodetector integrated with a grating coupler on silicon-on-insulator.

We propose the design of a composite device structure with germanium-based (Ge-based) waveguide photodetectors integrated with grating couplers on a silicon-on-insulator platform. The finite-difference time-domain method is used to establish simulation models and optimize the design of the waveguide detector and grating coupler. For the grating coupler, by adjusting the size parameters to the optimal value and combining the advantages of the nonuniform grating and the Bragg reflector structure, the peak coupling efficiency reaches 85% at 1550 nm and 75.5% at 2000 nm, which is, respectively, 31.3% and 14.6% higher than that of uniform grating. For the waveguide detector, a germanium-tin (GeSn) alloy was introduced to replace Ge as the active absorption layer at 1550 and 2000 nm, which not only broadened the detection range and significantly improved the light absorption of the detector but also realized the near-complete light absorption of the GeSn alloy when the device length was 10 µm. These results make it possible to miniaturize the device structure of Ge-based waveguide photodetectors.

Diverse field-effect characteristics and negative differential transconductance in a graphene/WS2/Au phototransistor with a Ge back gate.

We propose an infrared-sensitive negative differential transconductance (NDT) phototransistor based on a graphene/WS2/Au double junction with a SiO2/Ge gate. By changing the drain bias, diverse field-effect characteristics can be achieved. Typical p-type and n-type behavior is obtained under negative and positive drain bias, respectively. And NDT behavior is observed in the transfer curves under positive drain bias. It is believed to originate from competition between the top and bottom channel currents in stepped layers of WS2 at different gate voltages. Moreover, this phototransistor shows a gate-modulated rectification ratio of 0.03 to 88.3. In optoelectronic experiments, the phototransistor exhibits a responsivity of 2.76 A/W under visible light at 532 nm. By contrast, an interesting negative responsivity of -29.5 µA/W is obtained and the NDT vanishes under illumination by infrared light at 1550 nm. A complementary inverter based on two proposed devices of the same structure is constructed. The maximum voltage gain of the complementary inverter reaches 0.79 at a supply voltage of 1.5 V. These results demonstrate a new method of realizing next-generation two- and three-dimensional electronic and optoelectronic multifunctional devices.

Adverse events of bevacizumab for triple negative breast cancer and HER-2 negative metastatic breast cancer: A meta-analysis.

Background: Triple-negative breast cancer (TNBC) and HER-2 negative metastatic breast cancer (HER-2 negative MBC) are intractable to various treatment schemes. Bevacizumab as a novel anti-VEGF drug, its safety for these two high-risk breast cancers remains controversial. Therefore, we conducted this meta-analysis to assess the safety of Bevacizumab for TNBC and HER-2 negative MBC. Methods: We searched Medline, Embase, Web of science and Cochrane databases updated to 1 Oct 2022 for relevant randomized controlled trials (RCTs). In all, 18 RCTs articles with 12,664 female patients were included. We used any grade Adverse Events (AEs) and grade ≥3 AEs to assess the AEs of Bevacizumab. Results: Our study demonstrated that the application of Bevacizumab was associated with increased incidence of grade ≥3 AEs (RR = 1.37, 95% CI 1.30-1.45, Rate: 52.59% vs. 41.32%). Any grade AEs (RR = 1.06, 95% CI 1.04-1.08, Rate: 64.55% vs. 70.59%) did not show a significant statistical difference in both overall results and among the subgroups. In subgroup analysis, HER-2 negative MBC (RR = 1.57, 95% CI 1.41-1.75, Rate: 39.49% vs. 25.6%), dosage over 15 mg/3w (RR = 1.44, 95% CI 1.07-1.92, Rate: 28.67% vs. 19.93%) and endocrine therapy (ET) (RR = 2.32, 95% CI 1.73-3.12, Rate: 31.17% vs. 13.42%) were associated with higher risk of grade ≥3 AEs. Of all graded ≥3 AEs, proteinuria (RR = 9.22, 95%CI 4.49-18.93, Rate: 4.22% vs. 0.38%), mucosal inflammation (RR = 8.12, 95%CI 2.46-26.77, Rate: 3.49% vs. 0.43%), palmar-plantar erythrodysesthesia syndrome (RR = 6.95, 95%CI 2.47-19.57, Rate: 6.01% vs. 0.87%), increased Alanine aminotransferase (ALT) (RR = 6.95, 95%CI 1.59-30.38, Rate: 3.13% vs. 0.24%) and hypertension (RR = 4.94, 95%CI 3.84-6.35, Rate: 9.44% vs. 2.02%) had the top five risk ratios. Conclusion: The addition of Bevacizumab for TNBC and HER-2 negative MBC patients showed an increased incidence of AEs especially for grade ≥3 AEs. The risk of developing different AEs varies mostly dependent on the type of breast cancer and combined therapy. Systematic Review Registration: [https://www.crd.york.ac.uk/PROSPERO/#recordDetails], identifier [CRD42022354743].

Self-Powered Bidirectional Photoresponse in High-Detectivity WSe2 Phototransistor with Asymmetrical van der Waals Stacking for Retinal Neurons Emulation.

An artificial retina system shows a promising potential to achieve fast response, low power consumption, and high integration density for vision sensing systems. Optoelectronic sensors, which can emulate the neurobiological functionalities of retinal neurons, are crucial in the artificial retina systems. Here, we propose a WSe2 phototransistor with asymmetrical van der Waals (vdWs) stacking that can be used as an optoelectronic sensor in artificial retina systems. Through the utilization of the gate-tunable self-powered bidirectional photoresponse of this phototransistor, the neurobiological functionalities of both bipolar cells and cone cells, as well as the hierarchical connectivity between these two types of retinal neurons, are successfully mimicked by a single device. This self-powered bidirectional photoresponse is attributed to the asymmetrical vdWs stacking structure, which enables the transition from an n-p to p+-p homojunction in the WSe2 channel under different polarities of gate bias. Moreover, the detectivity and ON/OFF ratio of this phototransistor reach as high as 1.8 × 1013 Jones and 5.3 × 104, respectively, and a rise/fall time <80 µs is achieved, as well, which reveals good photodetection performance. The proof of this device provides a pathway for the future development of neuromorphic vision devices and systems.

Influence of metal-semiconductor junction on the performances of mixed-dimensional MoS2/Ge heterostructure avalanche photodetector.

The two-dimensional/three-dimensional van der Waals heterostructures provide novel optoelectronic properties for the next-generation of information devices. Herein, MoS2/Ge heterojunction avalanche photodetectors are readily obtained. The device with an Ag electrode at MoS2 side exhibits more stable rectification characteristics than that with an Au electrode. The rectification radio greater than 103 and a significant avalanche breakdown are observed in the device. The responsivity of 170 and 4 A/W and the maximum gain of 320 and 13 are obtained under 532 and 1550 nm illumination, respectively. Such photoelectric properties are attributed to the carrier multiplication at a Ge/MoS2 junction due to an avalanche breakdown. The mechanism is confirmed by the Sentaurus TCAD-simulated I-V characteristics.

Exstrophy-Epispadias Complex With Isolated Ectopic Bowel Segment: A Case Series and Literature Review.

OBJECTIVE: To present a case series of the exstrophy-epispadias complex (EEC) with isolated ectopic bowel segment (IEBS) with the literature review, highlighting the clinical findings and treatments. MATERIALS AND METHODS: We present 3 cases of bladder exstrophy (BE) with IEBS in our institute and reviewed the literature in PubMed with the terms "("bladder exstrophy" OR "epispadias") AND ("visceral sequestration" OR "sequestered" OR "ectopic bowel")." RESULTS: There were 2 males and 1 female. The IEBS was detected by physical examination in 2 cases and by ultrasonography in another one. All cases were BE accompanying with lower abdominal mass which adhered to the bladder wall but was separated from the digestive system. All cases underwent the IEBS excision and BE repair simultaneously. Pathological result of IEBS suggested the histological structures of colon. There were totally 13 cases of EEC with IEBS reported in the literature, including 2 (15%) epispadias, 9 (69%) covered BE, 1 (8%) duplicate BE and 1 (8%) classic bladder exstrophy. Although their clinical manifestations were various, IEBS excision were safely conducted in all cases. CONCLUSION: EEC with IEBS is an extremely rare congenital malformation. Physical and imaging examinations are important for diagnoses. Surgical excision is safe and effective for managing IEBS.

Efficacy and Safety of Capecitabine for Triple-Negative Breast Cancer: A Meta-Analysis.

Background: Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer with limited treatment options and poor prognosis. Capecitabine, as a novel adjuvant chemotherapy for TNBCs, remains controversial. Therefore, we conducted this meta-analysis to assess the efficacy and safety of capecitabine for early-stage TNBCs combined with neo-/adjuvant chemotherapy. Methods: We searched Medline, Embase, Web of Science, and Cochrane databases updated on Mar 18, 2022 for relevant RCTs. In all, 11 RCTs with 5,175 patients were included. We used hazard ratios (HRs) and odds ratios (ORs) to assess the differences between disease-free survival (DFS), overall survival (OS), and adverse events. Results: Our study demonstrated significance differences in both DFS and OS (DFS: HR=0.77; 95% CI 0.68-0.86; OS: HR=0.73, 95% CI 0.63-0.85). In subgroup analysis, the lower dosage group showed higher DFS (HR=0.79, 95% CI 0.69-0.91), higher frequency (HR=0.72, 95%CI 0.62-0.83), and adjuvant chemotherapy (HR=0.74, 95% CI 0.65-0.84). However, capecitabine was also associated with a higher risk of diarrhea (OR=3.10, 95% CI 2.32-4.15), hand-foot syndrome (OR=25.79, 95% CI 15.32-43.42), and leukopenia (OR=2.08, 95% CI 1.13-3.84). Conclusion: The addition of capecitabine to early-stage TNBC patients receiving standard adjuvant chemotherapy showed significant DFS and OS improvement with tolerable adverse events. The lower dosage and higher frequency of capecitabine combined with adjuvant chemotherapy demonstrated a better survival outcome.

High-performance unbiased Ge metal-semiconductor-metal photodetector covered with asymmetric HfSe2 contact geometries.

A Ge metal-semiconductor-metal photodetector covered with asymmetric HfSe2 contact geometries has been proposed to realize high-performance unbiased photodetection at 1550 nm. At -1 V bias, the responsivity of this device shows a 71% improvement compared to the device without HfSe2. Moreover, the responsivity and detectivity of this device at zero bias can reach to 71.2 mA/W and 3.27×1010 Jones, respectively. Furthermore, the fall time of this device is 2.2 µs and 53% shorter than the device without HfSe2. This work provides a feasible way to develop unbiased Ge-based photodetectors in the near-IR communications band.

Discovery of Inhibitors of the Lipopolysaccharide Transporter MsbA: From a Screening Hit to Potent Wild-Type Gram-Negative Activity.

The dramatic increase in the prevalence of multi-drug resistant Gram-negative bacterial infections and the simultaneous lack of new classes of antibiotics is projected to result in approximately 10 million deaths per year by 2050. We report on efforts to target the Gram-negative ATP-binding cassette (ABC) transporter MsbA, an essential inner membrane protein that transports lipopolysaccharide from the inner leaflet to the periplasmic face of the inner membrane. We demonstrate the improvement of a high throughput screening hit into compounds with on-target single digit micromolar (µM) minimum inhibitory concentrations against wild-type uropathogenic Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae. A 2.98 Å resolution X-ray crystal structure of MsbA complexed with an inhibitor revealed a novel mechanism for inhibition of an ABC transporter. The identification of a fully encapsulated membrane binding site in Gram-negative bacteria led to unique physicochemical property requirements for wild-type activity.

Infrared broadband enhancement of responsivity in Ge photodetectors decorated with Au nanoparticles.

A broadband, high-performance infrared Ge photodetector decorated with Au nanoparticles (NPs) is proposed. Photoelectronic characterization demonstrated that the responsivity of devices decorated with Au NPs is as high as 3.95 A/W at a wavelength of 1550 nm. Compared with a Ge photodetector without Au NPs, the responsivity of a device decorated with Au NPs is significantly increased, i.e., by more than 10 times in the entire range of infrared communication wavelengths, including the O, E, S, C, L, and U bands. The increase is ascribed to type-II energy-band alignment between Ge covered with Au NPs and bare Ge, instead of the localized surface-plasmon-resonance effect. The type-II energy-band alignment enhances the spatial electron-hole separation and restrains the electron-hole recombination, thus a larger photocurrent is observed. These results reflect the potential of this approach for achieving broadband, high-performance Ge photodetectors operating in the near-infrared communication band.

Nanoscale growth of a Sn-guided SiGeSn alloy on Si (111) substrates by molecular beam epitaxy.

Here, SiGeSn nanostructures were grown via molecular beam epitaxy on a Si (111) substrate with the assistance of Sn droplets. Owing to the thermal effect and the compressive strain induced by a lattice mismatch, Si and Sn atoms were successfully incorporated into the Ge matrix during the Sn-guided Ge deposition process. A low growth temperature of 350 °C produced a variety of SiGeSn nanostructures of different sizes, attributed to the variation of the initial Sn droplet size. Using energy-dispersive X-ray spectroscopy, the Sn, Si and Ge contents of a defect-free SiGeSn nanoisland were approximately determined to be 0.05, 0.09 and 0.86, respectively. Furthermore, as the growth temperature increased past 600 °C, the growth direction of the nanostructure was changed thermally from out-of-plane to in-plane. Meanwhile, the stacked SiGeSn nanowires grown along the 〈112〉 direction remained defect-free, though some threading dislocations were observed in the smooth SiGeSn nanowires along the 〈110〉 direction. These results offer a novel method to grow Si-based SiGeSn nanostructures while possessing important implications for fabricating further optoelectronic devices.

[Ultrasonographic and clinical features of common testicular germ cell tumors in children].

OBJECTIVE: To study the ultrasonographic manifestations and clinical features of common pediatric testicular germ cell tumors (TGCT) in children. METHODS: We retrospectively analyzed the laboratory, ultrasonographic and clinical data on 92 children with TGCT diagnosed in Shanghai Children's Hospital from March 2013 to January 2019, and investigated the values of the serum alpha-fetoprotein (AFP) level and maximum diameter of tumors in the diagnosis of benign and malignant tumors using the ROC curve. RESULTS: Of the 92 cases of pediatric TGCT, 64 (69.6%) were pathologically confirmed as benign tumors, including 40 cases of teratoma (62.5%), 18 cases of epidermoid cyst (28.1%) and 6 cases of dermoid cyst (9.4%), and the other 28 (30.4%) as malignant neoplasms, including 26 cases of yolk sac tumor (YST, 92.9%) and 2 cases of mixed germ cell tumor (MGCT, 7.1%). Ultrasonography showed that 62.5% of the teratomas were cystic-solid mixed (25/40) and 32.5% solid masses (12/40), that 33.3% of the epidermoid cysts exhibited a typical sign of "onion ring" (6/18) and 22.2% that of capsular calcification (4/18), and that 42.3% of the YSTs displayed isoechoic (11/26), 30.9% hypoechoic (8/26) solid masses without calcium and 26.9% cystic anechoic lesions (7/26). Color Doppler blood flow imaging manifested abundant blood flow signals in most of the YSTs (25/26, 96.2%) but none in either the epidermoid or the dermoid cysts. The area under the ROC curve (AUC) of the serum AFP value was 0.985, with an optimal cutoff value of 124.2 ng/ml, and the sensitivity and specificity of AFP in the diagnosis of benign and malignant tumors were 92.9% and 93.7%, respectively. The AUC of the maximum diameter of the tumors was 0.796, with an optimal cutoff value of 2.7 cm, and the sensitivity and specificity of the maximum diameter of the tumors in the diagnosis of benign and malignant neoplasms were 57.1% and 93.7%, respectively. CONCLUSIONS: Ultrasonographic images have different characteristic manifestations for different pathological types of pediatric TGCT. Pediatric TGCT has a good prognosis and radical orchiectomy should be considered for the treatment of the tumors with serum AFP ≥ 124.2 ng/ml and a diameter ≥ 2.7 cm.

GexSi1-x virtual-layer enhanced ferromagnetism in self-assembled Mn0.06Ge0.94 quantum dots grown on Si wafers by molecular beam epitaxy.

Self-assembled Mn0.06Ge0.94 quantum dots (QDs) on a Si substrate or GexSi1-x virtual substrate (VS) were grown by molecular beam epitaxy. The GexSi1-x VS of different thicknesses and Ge compositions x were utilized to modulate the ferromagnetic properties of the above QDs. The MnGe QDs on GexSi1-x VS show a significantly enhanced ferromagnetism with a Curie temperature above 220 K. On the basis of the microstructural and magnetization results, the ferromagnetic properties of the QDs on GexSi1-x VS are believed to come from the intrinsic MnGe ferromagnetic phase rather than any intermetallic ferromagnetic compounds of Mn and Ge. At the same time, we found that by increasing the Ge composition x of GexSi1-x VS, the ferromagnetism of QDs grown on VS will markedly increase due to the improvements of hole concentration and Ge composition inside the QDs. These results are fundamentally important in the understanding and especially in the realization of high Curie temperature MnGe diluted magnetic semiconductors.

High-quality GeSn Layer with Sn Composition up to 7% Grown by Low-temperature Magnetron Sputtering for Optoelectronic Application.

In this paper, a high-quality sputtered-GeSn layer on Ge (100) with a Sn composition up to 7% was demonstrated. The crystallinity of the GeSn layer was investigated via high-resolution X-ray diffraction (HR-XRD) and the strain relaxation degree of the GeSn layer was evaluated to be approximately 50%. A novel method was also proposed to evaluate the averaged threading dislocation densities (TDDs) in the GeSn layer, which was obtained from the rocking curve of GeSn layer along the (004) plane. The photoluminescence (PL) measurement result shows the significant optical emission (1870 nm) from the deposited high-quality GeSn layer. To verify whether our deposited GeSn can be used for optoelectronic devices, we fabricated the simple vertical p-i-n diode, and the room temperature current-voltage (I-V) characteristic was obtained. Our work paves the way for future sputtered-GeSn optimization, which is critical for optoelectronic applications.

Optimization of Pan-Pim Kinase Activity and Oral Bioavailability Leading to Diaminopyrazole (GDC-0339) for the Treatment of Multiple Myeloma.

Pim kinases have been targets of interest for a number of therapeutic areas. Evidence of durable single-agent efficacy in human clinical trials validated Pim kinase inhibition as a promising therapeutic approach for multiple myeloma patients. Here, we report the compound optimization leading to GDC-0339 (16), a potent, orally bioavailable, and well tolerated pan-Pim kinase inhibitor that proved efficacious in RPMI8226 and MM.1S human multiple myeloma xenograft mouse models and has been evaluated as an early development candidate.

Disrupting Gram-Negative Bacterial Outer Membrane Biosynthesis through Inhibition of the Lipopolysaccharide Transporter MsbA.

There is a critical need for new antibacterial strategies to counter the growing problem of antibiotic resistance. In Gram-negative bacteria, the outer membrane (OM) provides a protective barrier against antibiotics and other environmental insults. The outer leaflet of the outer membrane is primarily composed of lipopolysaccharide (LPS). Outer membrane biogenesis presents many potentially compelling drug targets as this pathway is absent in higher eukaryotes. Most proteins involved in LPS biosynthesis and transport are essential; however, few compounds have been identified that inhibit these proteins. The inner membrane ABC transporter MsbA carries out the first essential step in the trafficking of LPS to the outer membrane. We conducted a biochemical screen for inhibitors of MsbA and identified a series of quinoline compounds that kill Escherichia coli through inhibition of its ATPase and transport activity, with no loss of activity against clinical multidrug-resistant strains. Identification of these selective inhibitors indicates that MsbA is a viable target for new antibiotics, and the compounds we identified serve as useful tools to further probe the LPS transport pathway in Gram-negative bacteria.