Ultra-high thermal stability InAs/GaAs quantum dot lasers grown on on-axis Si (001) with a record-high continuous-wave operating temperature of 150 °C.

Direct epitaxial growth of group III-V light sources with excellently thermal performance on silicon photonics chips promises low-cost, low-power-consumption, high-performance photonic integrated circuits. Here, we report on the achievement of ultra-high thermal stability 1.3 µm InAs/GaAs quantum dot (QD) lasers directly grown on an on-axis Si (001) with a record-high continuous-wave (CW) operating temperature of 150 °C. A GaAs buffer layer with a low threading dislocation density (TDD) of 4.3 × 106 cm-2 was first deposited using an optimized three-step growth method by molecular beam epitaxy. Then, an eight-layer QD laser structure with p-type modulation doping to enhance the temperature stability of the device was subsequently grown on the low TDD Si-based GaAs buffer layer. It is shown that the QD laser exhibits the ultra-high temperature stability with a characteristic temperature T0=∞ and T1=∞ in the wide temperature range of 10-75 °C and 10-140 °C, respectively. Moreover, a maximum CW operating temperature of up to 150 °C and a pulsed operating temperature of up to 160 °C are achieved for the QD laser. In addition, the QD laser shows a high CW saturation power of 50 mW at 85 °C and 19 mW at 125 °C, respectively.

Significantly enhanced performance of InAs/GaAs quantum dot lasers on Si(001) via spatially separated co-doping.

We report the significantly enhanced performance of InAs/GaAs quantum dot (QD) lasers on Si(001) by spatially separated co-doping, including n-doping in the QDs and p-doping in the barrier layers simultaneously. The QD lasers are a ridge waveguide of 6 × 1000 µm2 containing five InAs QD layers. Compared with p-doped alone laser, the co-doped laser exhibits a large reduction in threshold current of 30.3% and an increase in maximum output power of 25.5% at room temperature. In the range of 15°C-115°C (under 1% pulse mode), the co-doped laser shows better temperature stability with higher characteristic temperatures of threshold current (T0) and slope efficiency (T1). Furthermore, the co-doped laser can maintain stable continuous-wave ground-state lasing up to a high temperature of 115°C. These results prove the great potential of co-doping technique for enhancing silicon-based QD laser performances towards lower power consumption, higher temperature stability, and higher operating temperature, to boost the development of high-performance silicon photonic chips.

Low-loss c-axis oriented Zn0.72Mg0.28O nonlinear planar optical waveguides on silicon.

A material platform of highly c-axis oriented Zn1-xMgxO thin films is developed for nonlinear planar waveguides and electro-optic modulators on Si. Mg content in the film greatly influences the quality of film growth. The second harmonic generation measurement and Maker-fringe analysis reveal that the second-order nonlinear susceptibility tensor element χ33 of the annealed Zn0.72Mg0.28O is approximately 4.2 times larger than that of ZnO. The propagation loss of 633 nm wavelength light in the annealed air/Zn0.72Mg0.28O/SiO2 slab waveguide is 0.68 ± 0.09 dB/cm and 0.48 ± 0.03 dB/cm for the TE0 and TM0 modes, respectively. These results suggest the great potential of the c-axis oriented Zn0.72Mg0.28O nonlinear planar waveguides for applications in on-chip optical interconnects.

Role of lactate and lactate metabolism in liver diseases (Review).

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post­translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism­related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non­alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Shape and Composition Evolution in an Alloy Core-Shell Nanowire Heterostructure Induced by Adatom Diffusion.

A core-shell nanowire heterostructure is an important building block for nanowire-based optoelectronic devices. In this paper, the shape and composition evolution induced by adatom diffusion is investigated by constructing a growth model for alloy core-shell nanowire heterostructures, taking diffusion, adsorption, desorption and incorporation of adatoms into consideration. With moving boundaries accounting for sidewall growth, the transient diffusion equations are numerically solved by the finite element method. The adatom diffusions introduce the position-dependent and time-dependent adatom concentrations of components A and B. The newly grown alloy nanowire shell depends on the incorporation rates, resulting in both shape and composition evolution during growth. The results show that the morphology of nanowire shell strongly depends on the flux impingement angle. With the increase in this impingement angle, the position of the largest shell thickness on sidewall moves down to the bottom of nanowire and meanwhile, the contact angle between shell and substrate increases to an obtuse angle. Coupled with the shell shapes, the composition profiles are shown as non-uniform along both the nanowire and the shell growth directions, which can be attributed to the adatom diffusion of components A and B. The impacts of parameters on the shape and composition evolution are systematically investigated, including diffusion length, adatom lifetime and corresponding ratios between components. This kinetic model is expected to interpret the contribution of adatom diffusion in growing alloy group-IV and group III-V core-shell nanowire heterostructures.

Improved performance of quantum dot solar cells by type-II InAs/GaAsSb structure with moderate Sb composition.

We demonstrate improved performance of quantum dot solar cells (QDSCs) by type-II InAs/GaAsSb structure. With a moderate Sb composition of 18% and high quality QDs, a high efficiency of 17.31% under AM1.5 G illumination is achieved, showing an improvement of 11.25% in efficiency relative to type-I InAs/InGaAs QDSC. This improvement can be attributed to a high fill factor (FF) of 72.37% compared to 63% of the latter because the type-II structure effectively suppresses carrier recombination losses in QDs. As Sb composition increases to 24%, the FF maintains at a high level of 72.67%, but the efficiency drops to 17% because the elevation of valence band (VB) in GaAsSb capping layer further enhances the hole confinement. And the confinement reduces external quantum efficiency (EQE) and short-circuit current density (Jsc). These results prove the potential of improving efficiency of QDSCs by type-II structure.

Optically Rough and Physically Flat Transparent Conductive Substrates with Strong Far-Field Scattering.

Optically rough and physically flat transparent conductive (OR-PF) substrates facilitate the performance improvement of optoelectronic devices and functional glasses via simultaneously enabling high-quality growth of functional layers and effective light management. This paper studies the effect of the interface morphology of the hole array pattern (HAP) and the pillar array pattern (PAP) on the far-field scattering properties of OR-PF substrates fabricated by spin-coating Al-doped ZnO (AZO) on nanoimprint-patterned glasses for improving the performance of superstrate-type thin-film solar cells. Theoretical calculation based on bidirectional scattering distribution function predicts that HAP with a period of 1.5 µm and a diameter of 1.3 µm [HAP(P1.5D1.3)] and the PAP(P1.0D0.5) interface morphology have a haze ratio in transmission (HT) of around 64% and a scatter angle of larger than 34°. The fabricated AZO/HAP(P1.5D1.3) and AZO/PAP(P1.0D0.5) show a flat surface with a σrms of less than 9 nm, a high visible light transmittance of over 86%, a sheet resistance of about 30 Ω/sq, and strong far-field scattering. In particular, AZO/PAP(P1.0D0.5) possesses an average HT of over 11% at the wavelength range of 600-850 nm and an angular intensity distribution of over 1.5% at an azimuthal angle of around 55°, indicating stronger far-field scattering than the conventional pyramid-textured B-doped ZnO (BZO/F). Compared to the flat substrate, AZO/PAP generates an implied Jsc gain of 16.2% in a CH3NH3PbI3 photoactive layer with a thickness of 300 nm under normal incidence at the wavelength range of 550-800 nm. For 60° incidence, AZO/PAP(P1.0D0.5) enables an implied Jsc gain of 2.3% with respect to BZO/F. As applied to the front electrode of CH3NH3PbI3 thin-film solar cells, compared to BZO/F, AZO/PAP(P1.0D0.5) would enable a gain of up to 16.7 and 11.2% in photoelectric conversion efficiency for the 0 and 60° incidence, respectively.

Carbon ion radiotherapy for recurrent ameloblastoma: A case report.

Ameloblastoma is a kind of benign, odontogenic tumor of epithelial origin, and surgery is mainstay treatment method; however, recurrence is common, and usually the treatment for recurrence is still surgery. We report on a patient of recurrent ameloblastoma treated with carbon ion radiation therapy and achieved a good efficacy. A 25-year-old female with relapse of an ameloblastoma was referred to the Wuwei Heavy Ion Center for carbon ion therapy. She had been initially diagnosed with ameloblastoma 8 years ago and underwent operation of right mandible ameloblastoma. After she transferred to our center, she accepted a dose of 60 GyE carbon ion radiation therapy, and the efficacy is good. Carbon ion radiation therapy can be an effective treatment option for ameloblastoma.

Carbon ion radiotherapy for recurrent calf myxoid liposarcoma: a case report.

Liposarcoma (LPS) is the most common soft tissue sarcoma. Myxoid LPS (MLPS) is the second most common subtype of LPS and accounts for 25% to 50% of all LPSs. Like most other soft tissue sarcomas, the mainstay of treatment for LPS is inevitably surgery. Multidisciplinary approaches, including surgery, chemotherapy, and radiotherapy, have been successful in the treatment of LPS during the last three decades. Even so, recurrence of LPS remains challenging. Carbon ion beams produce increased energy deposition at the end of their range to form a Bragg peak while minimizing irradiation damage to surrounding tissues, which facilitates more precise dosage and localization than that achieved with photon beams. Furthermore, carbon ion beams have high relative biologic effectiveness. We herein describe a patient who developed recurrent MLPS in the right calf after two surgeries and underwent carbon ion radiotherapy (CIRT), achieving complete disappearance of the tumor. The patient developed Grade 1 radiation dermatitis 30 days after CIRT, but no other acute toxicities were observed. The tumor had completely disappeared by 120 days after CIRT, and the patient remained disease-free for 27 months after CIRT. The CARE guidelines were followed in the reporting of this case.

Carbon ion radiotherapy for synchronous choroidal melanoma and lung cancer: A case report.

BACKGROUND: Despite being the most common intraocular malignancy among adults, choroidal melanoma is a rare cancer type, even more so when accompanied by lung cancer. We report a patient with synchronous choroid melanoma and lung cancer treated with carbon ion radiotherapy (CIRT). CASE SUMMARY: A 41-year-old woman was transferred to our center with a diagnosis of choroidal melanoma in her right eye. During the examination, we found a right lung tumor that was histologically diagnosed as lung cancer. The patient was treated with CIRT for both malignant neoplasms. The CIRT dose was 70 photon equivalent doses (GyE) in five fractions for the right eye choroidal melanoma and 72 GyE in 16 fractions for the right lung cancer. At 3 mo after CIRT, the choroidal melanoma completely disappeared, as did the right lung cancer 7 mo after; the patient was in complete remission. CONCLUSION: CIRT may be an effective treatment for double primary lung cancer and choroid melanoma.

Carbon ion radiotherapy for bladder cancer: A case report.

BACKGROUND: Radical cystectomy is considered the first choice for the treatment of muscle-invasive bladder cancer. However, for some patients who have lost the indications for surgery, external beam radiotherapy is a non-invasive and effective treatment. CASE SUMMARY: A 76-year-old patient with bladder cancer who had serious comorbidities and could not tolerate surgery or chemotherapy came to the Wuwei Heavy Ion Center. He received carbon ion radiotherapy (CIRT) with a whole-bladder dose of 44 GyE and tumor boost of 20 GyE. When he finished CIRT, his bladder cancer-related hematuria completely disappeared, and computed tomography examination showed that the tumor had obviously decreased in size. At the 3-mo follow-up, the tumor disappeared, and there were no acute or late adverse events. CIRT was well tolerated in this patient. CONCLUSION: CIRT may allow for avoiding resection and was well tolerated with curative outcomes.

Bystander effect and abscopal effect in recurrent thymic carcinoma treated with carbon-ion radiation therapy: A case report.

BACKGROUND: Although the bystander effect and abscopal effect are familiar in medicine, they are relatively rare in clinical practice. Herein, we report the case of a patient who demonstrated an obvious bystander effect and abscopal effect response following carbon-ion irradiation for recurrent thymic carcinoma. CASE SUMMARY: A 44-year-old female presented with shortness of breath. Eleven years prior, she was diagnosed with athymic tumor located in the anterosuperior mediastinum. She underwent extensive tumor resection, and the postoperative pathologic diagnosis was thymic carcinoma. She was administered 50 Gy/25 Fx of postoperative radiation. In 2019, she was diagnosed with a recurrence of thymic carcinoma, with multiple recurrent nodules and masses in the left thoracic chest and peritoneal cavity, the largest of which was in the diaphragm pleura proximal to the pericardium, with a size of 6.7 cm × 5.3 cm × 4.8 cm. She received carbon-ion radiotherapy. After carbon-ion radiotherapy treatment, the treated masses and the untreated masses were observed to have noticeably shrunk on the day of carbon-ion radiotherapy completion and on follow-up imaging. We followed the CARE Guidelines for consensus-based clinical case reporting guideline development and completed the CARE Checklist of information to report this case. CONCLUSION: This report is the first of obvious abscopal and bystander effects following carbon-ion irradiation in a human patient, and further research is needed to better elucidate the mechanisms of bystander and abscopal effects.

Discovery of First-In-Class Potent and Selective Tropomyosin Receptor Kinase Degraders.

We report compounds 5 (CG416) and 6 (CG428) as two first-in-class tropomyosin receptor kinase (TRK) degraders that target the intracellular kinase domain of TRK. Degraders 5 and 6 reduced levels of the tropomyosin 3 (TPM3)-TRKA fusion protein in KM12 colorectal carcinoma cells and inhibited downstream PLCγ1 signaling at sub-nanomolar concentrations. Both degraders also degraded human wild-type TRKA with similar potency. Interestingly, both degraders, especially 6, showed selectivity for the degradation of endogenous TPM3-TRKA over ectopically expressed ATP/GTP binding protein-like 4 (AGBL4)-TRKB or ETS variant transcription factor 6 (ETV6)-TRKC fusion proteins in KM12 cells. Global proteomic profiling assays demonstrated that 5 is highly selective for the intended target. TPM3-TRKA protein degradation induced by 5 and 6 was further confirmed to be mediated through cereblon and the ubiquitin-proteasome system. Compared with the parental TRK kinase inhibitor, both degraders exhibited higher potency for inhibiting growth of KM12 cells. Moreover, both 5 and 6 showed good plasma exposure levels in mice. Therefore, 5 and 6 are valuable chemical tool compounds for investigating the in vivo function of TRK fusion during tumorigenesis. Our study also paves the way for pharmacological degradation of TRK.

Surface Modification of Al-Doped ZnO Transparent Conducive Thin Films with Polycrystalline Zinc Molybdenum Oxide.

High-work function (WF) transparent conductive thin films improve the performance of solar cells and organic light-emitting diodes by facilitating interfacial charge carrier transport. Al-doped ZnO (AZO) becomes a very promising transparent conductive material because of nontoxicity, abundant material resources, and low cost. To increase the WF of AZO without enhancing the series resistance of the device, a high-WF and low-resistance surface modifier of polycrystalline zinc molybdenum oxide (ZMO) was developed by utilizing thermal evaporation of MoO3 on the surface of AZO and a subsequent two-step annealing treatment. The first step of air annealing causes the formation of monoclinic ZnMoO4 nanocrystals in the ZMO modifier. This improves the WF of AZO from 3.83 to 4.86 eV by increasing the group electronegativity and cation oxidation state. Furthermore, the second step of N2 annealing decreases the resistivity of the polycrystalline ZMO by increasing the donor states of oxygen vacancies. The surface modification effect is verified by applying the ZMO-modified AZO to the front electrode of hydrogenated amorphous silicon thin-film solar cells. The low-resistance polycrystalline ZMO modifier not only increases light harvesting in the solar cells by improving interfacial refractive index matching but also improves the open-circuit voltage by modifying the interfacial band alignment. In particular, the modifier increases the fill factor by ca. 13% by reducing the series resistance of the device. These enable a gain of ca. 23% in photoelectric conversion efficiency compared to the unmodified AZO. The results suggest the feasibility to tune the WF and conductivity of a material independently.

Fused Deposition Modeling (FDM) 3D Printed Tablets for Intragastric Floating Delivery of Domperidone.

The aim of this study was to explore the feasibility of fused deposition modeling (FDM) 3D printing to prepare intragastric floating sustained release (FSR) tablets. Domperidone (DOM), an insoluble weak base, was chosen as a model drug to investigate the potential of FSR in increasing its oral bioavailability and reducing its administration frequency. DOM was successfully loaded into hydroxypropyl cellulose (HPC) filaments using hot melt extrusion (HME). The filaments were then printed into hollow structured tablets through changing the shell numbers and the infill percentages. Physical characterization results indicated that the majority of DOM gradually turned into the amorphous form during the fabrication process. The optimized formulation (contain 10% DOM, with 2 shells and 0% infill) exhibited the sustained release characteristic and was able to float for about 10 h in vitro. Radiographic images showed that the BaSO4-labeled tablets were retained in the stomach of rabbits for more than 8 h. Furthermore, pharmacokinetic studies showed the relative bioavailability of the FSR tablets compared with reference commercial tablets was 222.49 ± 62.85%. All the results showed that FDM based 3D printing might be a promising way to fabricate hollow tablets for the purpose of intragastric floating drug delivery.

A Three-Pulse Release Tablet for Amoxicillin: Preparation, Pharmacokinetic Study and Physiologically Based Pharmacokinetic Modeling.

BACKGROUND: Amoxicillin is a commonly used antibiotic which has a short half-life in human. The frequent administration of amoxicillin is often required to keep the plasma drug level in an effective range. The short dosing interval of amoxicillin could also cause some side effects and drug resistance, and impair its therapeutic efficacy and patients' compliance. Therefore, a three-pulse release tablet of amoxicillin is desired to generate sustained release in vivo, and thus to avoid the above mentioned disadvantages. METHODS: The pulsatile release tablet consists of three pulsatile components: one immediate-release granule and two delayed release pellets, all containing amoxicillin. The preparation of a pulsatile release tablet of amoxicillin mainly includes wet granulation craft, extrusion/spheronization craft, pellet coating craft, mixing craft, tablet compression craft and film coating craft. Box-Behnken design, Scanning Electron Microscope and in vitro drug release test were used to help the optimization of formulations. A crossover pharmacokinetic study was performed to compare the pharmacokinetic profile of our in-house pulsatile tablet with that of commercial immediate release tablet. The pharmacokinetic profile of this pulse formulation was simulated by physiologically based pharmacokinetic (PBPK) model with the help of Simcyp®. RESULTS AND DISCUSSION: Single factor experiments identify four important factors of the formulation, namely, coating weight of Eudragit L30 D-55 (X1), coating weight of AQOAT AS-HF (X2), the extrusion screen aperture (X3) and compression forces (X4). The interrelations of the four factors were uncovered by a Box-Behnken design to help to determine the optimal formulation. The immediate-release granule, two delayed release pellets, together with other excipients, namely, Avicel PH 102, colloidal silicon dioxide, polyplasdone and magnesium stearate were mixed, and compressed into tablets, which was subsequently coated with Opadry® film to produce pulsatile tablet of amoxicillin. In vitro release study firstly indicated a three-pulse release profile of the tablet. Later the pulse tablet was found to generate the sustained release of amoxicillin in beagle dogs. Furthermore, the Simcyp® software was used to simulate the in vivo concentration time curve model of the three-pulse release tablet for amoxicillin in both human and beagle dog. The prediction by PBPK model nicely fitted the observation in human and beagle dog. CONCLUSIONS: This study has demonstrated the interrelation of factors affecting the pulsatile formulation of amoxicillin using a Box-Behnken design. The three-pulse release tablets of amoxicillin were proven to generate pulsatile release in vitro and sustained release in vivo. This formulation was also found to extend the effective plasma concentration in human compared to the tablet of immediate release based on the simulation data by PBPK modeling. This study provides an example of using PBPK to guide the development of pulsatile dosage forms.

A Novel Isoquinoline Derivative Anticancer Agent and Its Targeted Delivery to Tumor Cells Using Transferrin-Conjugated Liposomes.

We have screened 11 isoquinoline derivatives and α-methylene-γ-butyrolactones using the 3-(4,5-dimethylthi-azol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) cytotoxicity assay in HeLa and HEK-293T cells. Compound 2 was identified as potential anticancer agent. To further improve its therapeutic potential, this agent was incorporated into transferrin (Tf)-conjugated liposomes (LPs) for targeted delivery to tumor cells. We have demonstrated Tf-LP-Compound 2 have superior antitumor activity compared to non-targeted controls and the free drug. These data show Tf-LP-Compound 2 to be a promising agent that warrants further evaluation.