Survival Predictive Nomograms for Non-Surgical Brain Metastases Patients From Non-Small Cell Lung Cancer Receiving Radiotherapy: A Population-Based Study.

OBJECTIVE: A high number of Non-Small Cell Lung Cancer (NSCLC) patients with brain metastasis who have not had surgery often have a negative outlook. Radiotherapy remains a most common and effective method. Nomograms were developed to forecast the cancer-specific survival (CSS) and overall survival (OS) in NSCLC individuals with nonoperative brain metastases who underwent radiotherapy. METHODS: Information was gathered from the Surveillance, Epidemiology, and End Results (SEER) database about patients diagnosed with NSCLC who had brain metastases not suitable for surgery. Nomograms were created and tested using multivariate Cox regression models to forecast CSS and OS at intervals of 1, 2, and 3 years. RESULTS: The research involved 3413 individuals diagnosed with NSCLC brain metastases who had undergone radiotherapy but had not experienced surgery. These participants were randomly divided into two categories. The analysis revealed that gender, age, ethnicity, marital status, tumor location, tumor laterality, tumor grade, histology, T stage, N stage, chemotherapy, tumor size, lung metastasis, bone metastasis, and liver metastasis were significant independent predictors for OS and CSS. The C-index for the training set for predicting OS was .709 (95% CI, .697-.721), and for the validation set, it was .705 (95% CI, .686-.723), respectively. The C-index for predicting CSS was .710 (95% CI, .697-.722) in the training set and .703 (95% CI, .684-.722) in the validation set, respectively. The nomograms model, as suggested by the impressive C-index, exhibits outstanding differentiation ability. Moreover, the ROC and calibration curves reveal its commendable precision and distinguishing potential. CONCLUSIONS: For the first time, highly accurate and reliable nomograms were developed to predict OS and CSS in NSCLC patients with non-surgical brain metastases, who have undergone radiotherapy treatment. The nomograms may assist in tailoring counseling strategies and choosing the most effective treatment method.

All-natural 2D nanofluidics as highly-efficient osmotic energy generators.

Two-dimensional nanofluidics based on naturally abundant clay are good candidates for harvesting osmotic energy between the sea and river from the perspective of commercialization and environmental sustainability. However, clay-based nanofluidics outputting long-term considerable osmotic power remains extremely challenging to achieve due to the lack of surface charge and mechanical strength. Here, a two-dimensional all-natural nanofluidic (2D-NNF) is developed as a robust and highly efficient osmotic energy generator based on an interlocking configuration of stacked montmorillonite nanosheets (from natural clay) and their intercalated cellulose nanofibers (from natural wood). The generated nano-confined interlamellar channels with abundant surface and space negative charges facilitate selective and fast hopping transport of cations in the 2D-NNF. This contributes to an osmotic power output of ~8.61 W m-2 by mixing artificial seawater and river water, higher than other reported state-of-the-art 2D nanofluidics. According to detailed life cycle assessments (LCA), the 2D-NNF demonstrates great advantages in resource consumption (1/14), greenhouse gas emissions (1/9), and production costs (1/13) compared with the mainstream 2D nanofluidics, promising good sustainability for large-scale and highly-efficient osmotic power generation.

The Role of Grain Boundaries on Ion Migration and Charge Recombination in Halide Perovskites.

Grain boundaries (GBs) have a significant role in polycrystalline perovskite solar cells (PSCs). However, there is ongoing debate regarding the impact of GBs on the performance and long-term stability of PSCs. Employing the first-principles molecular dynamics for perovskites, the iodine vacancy defect migrations both in bulk and at GBs are investigated. i) The positive iodine vacancy (VI +) is found that have both lower formation energy (1.4 eV) and activation energy (0.18 eV) than those of neutral iodine vacancy (VI), statistically. It indicated the VI + acts as the dominant migrated iodine vacancy rather than VI; ii) the iodine vacancy at GBs has ≈0.48 eV higher activation energy than those in bulk, which leads to the accumulation of iodine vacancy at GBs; iii) the presence of VI + result in a 3-fold increase in charge recombination ratio at GBs, compared to pristine PSCs. Based on quantum molecular dynamics statistical results, which are consistent with experimental measurements, insights into iodine vacancy migration both at GBs and in the bulk are gained. This understanding can be valuable for defects engineering related to ion migration, in order to improve the long-term stability and promote the performance of PSCs.

Dormancy and double-activation strategy for construction of high-performance mixed-matrix membranes.

Mixed-matrix membranes (MMMs) have the potential for energy-efficient gas separation by matching the superior mass transfer and anti-plasticization properties of the fillers with processability and scaling up features of the polymers. However, construction of high-performance MMMs has been prohibited due to low filler-loading and the existence of interfacial defects. Here, high MOF-loaded, i.e., 55 wt %, MMMs are developed by a 'dormancy and double-activation' (DDA) strategy. High MOF precursor concentration suppresses crystallization in the membrane casting solution, realizing molecular level mixing of all components. Then, the polymeric matrix was formed with uniform encapsulation of MOF nutrients. Subsequently, double-activation was employed to induce MOF crystallization: the alkali promotes MOFs nucleation to harvest small porous nanocrystals while excessive ligands activate the metal ions to enhance the MOFs conversion. As such, quasi-semi-continuous mass transfer channels can be formed in the MMMs by the connected MOFs nanocrystals to boost the gas permeability. The optimized MMM shows significantly ameliorated CO2 permeability, i.e., 2841 Barrer, five-fold enhancement compared with pristine polymer membrane, with a good CO2 /N2 selectivity of 36. Besides, the nanosized MOFs intensify their interaction with polymer chains, endowing the MMMs with good anti-plasticization behaviour and stability, which advances practical application of MMMs in carbon capture.

First case report of Candida guilliermondii native left-sided valve endocarditis.

Endocarditis, a life-threatening inflammation of the endocardium, is incited by bacteria, fungi, or other pathogenic microorganisms. Fungal endocarditis closely mirrors bacterial endocarditis in clinical signs and symptoms, leading to potential misdiagnoses. Here, we unveil the inaugural confirmed instance of native left-sided valve endocarditis attributed to Candida guilliermondii. Diagnosis was substantiated through valvular biopsies, blood and vegetative cultures. Treatment encompassed surgical excision of vegetations along with a six-week regimen of fluconazole administration (12 mg/kg/day), followed by 4 years of meticulous monitoring, resulting in sustained patient recovery.

Advancing cardiac regeneration through 3D bioprinting: methods, applications, and future directions.

Cardiovascular diseases (CVDs) represent a paramount global mortality concern, and their prevalence is on a relentless ascent. Despite the effectiveness of contemporary medical interventions in mitigating CVD-related fatality rates and complications, their efficacy remains curtailed by an array of limitations. These include the suboptimal efficiency of direct cell injection and an inherent disequilibrium between the demand and availability of heart transplantations. Consequently, the imperative to formulate innovative strategies for cardiac regeneration therapy becomes unmistakable. Within this context, 3D bioprinting technology emerges as a vanguard contender, occupying a pivotal niche in the realm of tissue engineering and regenerative medicine. This state-of-the-art methodology holds the potential to fabricate intricate heart tissues endowed with multifaceted structures and functionalities, thereby engendering substantial promise. By harnessing the prowess of 3D bioprinting, it becomes plausible to synthesize functional cardiac architectures seamlessly enmeshed with the host tissue, affording a viable avenue for the restitution of infarcted domains and, by extension, mitigating the onerous yoke of CVDs. In this review, we encapsulate the myriad applications of 3D bioprinting technology in the domain of heart tissue regeneration. Furthermore, we usher in the latest advancements in printing methodologies and bioinks, culminating in an exploration of the extant challenges and the vista of possibilities inherent to a diverse array of approaches.

Cardiac self-limiting rhabdomyomas in a neonatal patient with tuberous sclerosis complex: a case report with negative genetic testing.

Background: Tuberous Sclerosis Complex (TSC) is a hereditary condition that leads to the development of non-malignant neoplasms in various organs, including cardiac rhabdomyomas, which can cause significant complications. Case presentation: This report describes the case of a 15-day-old male neonate who was hospitalized due to intracardiac masses and brain lesions, despite the absence of TSC gene mutations. The patient's mother exhibited facial angiofibromas, a common feature of TSC. Over a 2-year follow-up period, spontaneous regression of the cardiac tumor was observed. Conclusions: This case illustrates that not all TSC cases exhibit detectable TSC gene mutations. Current treatment strategies, such as mTOR inhibitors, offer potential effectiveness in managing associated cardiac rhabdomyomas. Further research should focus on evaluating the therapeutic potential of these inhibitors.

The resolutions of drive-level capacitance profiling technique.

Recently, the drive level capacitance profiling (DLCP) technique has been proven to be effective in resolving the spatial and energetic distributions of defects through feasible measurements. However, the discussion on its ranges and resolutions is still missing, which is urgent in evaluating the validity of the calculated defect profiles. In this work, we propose a method to analyze the ranges and resolutions of DLCP. Assuming that the test instrument has more influence on the experimental results than the experimental environment, this method can be used to evaluate the resolution of DLCP for different test instruments. Through revisiting the equations involved in DLCP, we learned that the sources of the limits and resolutions are (1) the instrument system error and inherent resolution and (2) the device impedance. Consequently, from the study of device impedance and the measuring instrument system error, the resolutions of DLCP could be calculated according to the error propagation theory. We provide the spatial distribution of the minimum selection range of AC signal δV used by DLCP and the spatial resolution of DLCP technology. This method can be used to evaluate the resolution of DLCP for different test instruments.

A computational approach to fighting type 1 diabetes by targeting 2C Coxsackie B virus protein with flavonoids.

Autoimmune diabetes, well-known as type 1 insulin-dependent diabetic mellitus (T1D). T1D is a prolonged condition marked by an inadequate supply of insulin. The lack is brought on by pancreatic cell death and results in hyperglycemia. The immune system, genetic predisposition, and environmental variables are just a few of the many elements that contribute significantly to the pathogenicity of T1D disease. In this study, we test flavonoids against Coxsackie virus protein to cope the type 1 diabetes. After protein target identification we perform molecular docking of flavonoids and selected target (1z8r). then performed the ADMET analysis and select the top compound the base of the docking score and the ADMET test analysis. Following that molecular dynamics simulation was performed up to 300 ns. Root means square deviation, root mean square fluctuation, secondary structure elements, and protein-ligand contacts were calculated as post-analysis of simulation. We further check the binding of the ligand with protein by performing MM-GBSA every 10 ns. Lead compound CID_5280445 was chosen as a possible medication based on analysis. The substance is non-toxic, meets the ADMET and BBB likeness requirements, and has the best interaction energy. This work will assist researchers in developing medicine and testing it as a treatment for Diabetes Mellitus Type 1 brought on by Coxsackie B4 viruses by giving them an understanding of chemicals against these viruses.

AVPCD: a plant-derived medicine database of antiviral phytochemicals for cancer, Covid-19, malaria and HIV.

Serious illnesses caused by viruses are becoming the world's most critical public health issues and lead millions of deaths each year in the world. Thousands of studies confirmed that the plant-derived medicines could play positive therapeutic effects on the patients with viral diseases. Since thousands of antiviral phytochemicals have been identified as lifesaving drugs in medical research, a comprehensive database is highly desirable to integrate the medicinal plants with their different medicinal properties. Therefore, we provided a friendly antiviral phytochemical database AVPCD covering 2537 antiviral phytochemicals from 383 medicinal compounds and 319 different families with annotation of their scientific, family and common names, along with the parts used, disease information, active compounds, links of relevant articles for COVID-19, cancer, HIV and malaria. Furthermore, each compound in AVPCD was annotated with its 2D and 3D structure, molecular formula, molecular weight, isomeric SMILES, InChI, InChI Key and IUPAC name and 21 other properties. Each compound was annotated with more than 20 properties. Specifically, a scoring method was designed to measure the confidence of each phytochemical for the viral diseases. In addition, we constructed a user-friendly platform with several powerful modules for searching and browsing the details of all phytochemicals. We believe this database will facilitate global researchers, drug developers and health practitioners in obtaining useful information against viral diseases.

Prediction of sub-pyramid texturing as the next step towards high efficiency silicon heterojunction solar cells.

The interfacial morphology of crystalline silicon/hydrogenated amorphous silicon (c-Si/a-Si:H) is a key success factor to approach the theoretical efficiency of Si-based solar cells, especially Si heterojunction technology. The unexpected crystalline silicon epitaxial growth and interfacial nanotwins formation remain a challenging issue for silicon heterojunction technology. Here, we design a hybrid interface by tuning pyramid apex-angle to improve c-Si/a-Si:H interfacial morphology in silicon solar cells. The pyramid apex-angle (slightly smaller than 70.53°) consists of hybrid (111)0.9/(011)0.1 c-Si planes, rather than pure (111) planes in conventional texture pyramid. Employing microsecond-long low-temperature (500 K) molecular dynamic simulations, the hybrid (111)/(011) plane prevents from both c-Si epitaxial growth and nanotwin formation. More importantly, given there is not any additional industrial preparation process, the hybrid c-Si plane could improve c-Si/a-Si:H interfacial morphology for a-Si passivated contacts technique, and wide-applied for all silicon-based solar cells as well.

Engineer Nanoscale Defects into Selective Channels: MOF-Enhanced Li+ Separation by Porous Layered Double Hydroxide Membrane.

Two-dimensional (2D) membrane-based ion separation technology has been increasingly explored to address the problem of lithium resource shortage, yet it remains a sound challenge to design 2D membranes of high selectivity and permeability for ion separation applications. Zeolitic imidazolate framework functionalized modified layered double hydroxide (ZIF-8@MLDH) composite membranes with high lithium-ion (Li+) permeability and excellent operational stability were obtained in this work by in situ depositing functional ZIF-8 nanoparticles into the nanopores acting as framework defects in MLDH membranes. The defect-rich framework amplified the permeability of Li+, and the site-selective growth of ZIF-8 in the framework defects bettered its selectivity. Specifically speaking, the ZIF-8@MLDH membranes featured a high permeation rate of Li+ up to 1.73 mol m-2 h-1 and a desirable selectivity of Li+/Mg2+ up to 31.9. Simulations supported that the simultaneously enhanced selectivity and permeability of Li+ are attributed to changes in the type of mass transfer channels and the difference in the dehydration capacity of hydrated metal cations when they pass through nanochannels of ZIF-8. This study will inspire the ongoing research of high-performance 2D membranes through the engineering of defects.

Efficacy and safety of modified fasting therapy for weight loss in 2054 hospitalized patients.

OBJECTIVE: The aim of this study was to evaluate the efficacy and safety of modified fasting therapy, and a retrospective study was conducted to analyze changes in clinical indicators of hospitalized fasting patients. METHODS: A total of 2054 hospitalized fasting patients were enrolled in this observational study. All participants underwent 7 days of modified fasting therapy. The clinical efficacy biomarkers, safety indicators, and body composition were measured before and after fasting. RESULTS: The modified fasting therapy reduced body weight, BMI, abdominal circumference, systolic blood pressure, and diastolic blood pressure significantly. Blood glucose and indicators of body composition were improved to various extents (all p < 0.05). There was a small increase in liver function, kidney function, uric acid, electrolytes, blood count, coagulation, and uric biomarkers. Subgroup analysis results showed that cardiovascular diseases benefited from modified fasting therapy. CONCLUSIONS: At present this study is the largest retrospective population-based study about modified fasting therapy. The results from 2054 patients showed that the modified fasting therapy lasting 7 days was efficient and safe. It led to improvements in physical health and body weight-associated indicators, as well as body composition and relevant cardiovascular risk factors.

Synthesis and nitroxyl (HNO) donating properties of benzoxadiazole-based Piloty's acids.

Developing functional nitroxyl (HNO) donors play a significant role in the further exploration of endogenous HNO in biochemistry and pharmacology. In this work, two novel Piloty's acids (SBD-D1 and SBD-D2) were proposed by incorporating benzoxadiazole-based fluorophores, in order to achieve the dual-function of releasing both HNO and a fluorophore in situ. Under physiological conditions, both SBD-D1 and SBD-D2 efficiently donated HNO (t1/2 = 10.96 and 8.18 min, respectively). The stoichiometric generation of HNO was determined by both Vitamin B12 and phosphine compound trap. Interestingly, due to the different substitution groups on the aromatic ring, SBD-D1 with the chlorine showed no fluorescence emission, but SBD-D2 was strongly fluorescent due to the presence of the dimethylamine group. Specifically, the fluorescent signal would decrease during the release process of HNO. Moreover, theoretical calculations were performed to understand the emission difference. A strong radiation derived from benzoxadiazole with dimethylamine group due to the large transition dipole moment (∼4.3 Debye), while the presence of intramolecular charge transfer process in the donor with chlorine group caused a small transition dipole moment (<0.1 Debye). Finally, these studies would contribute to the future design and application of novel functional HNO donors for the exploration of HNO biochemistry and pharmacology.

Investigation on Preparation and Performance of High Ga CIGS Absorbers and Their Solar Cells.

Tandem solar cells usually use a wide band gap absorber for top cell. The band gap of CuIn(1-x)GaxSe2 can be changed from 1.04 eV to 1.68 eV with the ratio of Ga/(In+Ga) from 0 to 1. When the ratio of Ga/(In+Ga) is over 0.7, the band gap of CIGS absorber is over 1.48 eV. CIGS absorber with a high Ga content is a possible candidate one for the top cell. In this work, CuInGa precursors were prepared by magnetron sputtering with CuIn and CuGa targets, and CIGS absorbers were prepared by selenization annealing. The Ga/(In+Ga) is changed by changing the thickness of CuIn and CuGa layers. Additionally, CIGS solar cells were prepared using CdS buffer layer. The effects of Ga content on CIGS thin film and CIGS solar cell were studied. The band gap was measured by PL and EQE. The results show that using structure of CuIn/CuGa precursors can make the band gap of CIGS present a gradient band gap, which can obtain a high open circuit voltage and high short circuit current of the device. With the decrease in Ga content, the efficiency of the solar cell increases gradually. Additionally, the highest efficiency of the CIGS solar cells is 11.58% when the ratio of Ga/(In+Ga) is 0.72. The value of Voc is 702 mV. CIGS with high Ga content shows a great potential for the top cell of the tandem solar cell.

A Universal Microscopic Patterned Doping Method for Perovskite Enables Ultrafast, Self-Powered, Ultrasmall Perovskite Photodiodes.

Novel metal halide perovskite is proven to be a promising optoelectronic material. However, fabricating microscopic perovskite devices is still challenging because the perovskite is soluble with the photoresist, which conflicts with conventional microfabrication technology. The size of presently reported perovskite devices is about 50 µm. Limited by the large size of perovskite optoelectronic devices, they cannot be readily adopted in the fields of imaging, display, etc. Herein a universal microscopic patterned doping method is proposed, which can realize microscale perovskite devices. Rather than by the conventional doping method, in this study the local Fermi level of perovskite is modulated by the redistributing intrinsic ion defects via a polling voltage. A satisfactorily stable polarized ion distribution can be achieved by optimization of the perovskite material and polling voltage, resulting in ultrafast (40 µs), self-powered microscale (2 µm) photodiodes. This work sheds light on a route to fabricate integrated perovskite optoelectronic chips.

Theoretical investigation of electrochromic mechanism in D-A conjugated polymers in visible and infrared bands.

Electrochromic materials have been widely-applied in military camouflage and intelligent materials, in consideration of the multicolor display and infrared absorption. However, most of them have a narrow width of absorption spectra, and the electrochromic mechanism is still not well understood, especially in materials based on a copolymer structure in visible and infrared bands. Therefore, based on the polaron model, in order to enhance polarizability, we designed an "electronic donors-electronic acceptor" (D-A) type π-conjugated electrochromic polymer, which has an abundant color (wavelengths from 450 nm to 750 nm) with voltage range (from -0.2 V to 1.0 V). Employing first-principle calculations, we investigated the electrochromism of the polymer, which has a strong connection with the introduced new molecular orbital in the polaron (or cation), comparing with those in the neutral molecule. This study addressed the underlying mechanism for the electrochromic phenomenon and the behavior of the cation. It indicated the polaron molecular orbitals provide the photon absorption, whose energies are in the visible range and result in the electrochromic abundant color. In this work, we provide a molecular design for the adjustment of visible and infrared band absorption, which could have broad application in multicolor and infrared electrochromic materials.

Design of Intramolecular Dihedral Angle between Electronic Donor and Acceptor in Thermally Activated Delayed Fluorescence Molecules.

In order to improve the exciton utilization efficiency (ηexc) of organic light-emitting materials, we addressed the ideal donor-acceptor dihedral angle (θD-A) in the TADF molecule by striking a balance between two photophysical processes. One is the conversion of triplet excitons into singlet excitons, and the other is the radiative process from a low-lying excited state to the ground state. Using a combination of first-principles calculations and molecular dynamics simulations, we investigated the impact of θD-A on the splitting energy and spin-orbit coupling between singlet and triplet excitons as well as the transition dipole moment for carbazole benzonitrile (CzBN) derivatives. By comparison with the reverse intersystem crossing rate (krISC), fluorescence emission rate (kr), and ηexc, we proposed a potential highest ηexc (of 94.4%) with the ideal θD-A of 77° for blue light CzBN derivatives; the calculated results have a good agreement with experimental measurement. The structure-efficiency physical connection between the molecular structure (θD-A) and efficiency provided an ideal parameter for a potential candidate for blue TADF-OLED materials.

YWHAE/14-3-3ε crotonylation regulates leucine deprivation-induced autophagy.

Macroautophagy/autophagy is an important process responsible for protein turnover and cell survival in amino acid-deprived conditions, especially for leucine (Leu). With the dramatic advances in mass spectrometry, many new post-translational modifications (PTMs) have been identified. However, whether these PTMs regulate autophagy remains unclear. Here we found global lysine crotonylation levels are significantly upregulated during Leu deprivation-induced autophagy. A comprehensive crotonylome profiling showed that YWHA/14-3-3 proteins are significantly enriched in the Leu regulated-crotonylome. The inhibition of YWHAE/14-3-3ε crotonylation by mutating two crotonylated sites to arginine, K73R K78R, significantly attenuates autophagy induced by Leu deprivation. Molecular dynamics suggest that YWHAE K73 and K78 crotonylations decrease protein conformation and thermodynamic stability. Moreover, we found crotonylation of YWHAE releases PPM1B to dephosphorylate ULK1 and consequently activate autophagy. Decrotonylation of YWHAE is mediated by HDAC7 whose activity is inhibited significantly by Leu deprivation. Taken together, our finding reveals a critical role of YWHAE crotonylation in Leu deprivation-induced autophagy.

Integrated Uniformly Microporous C4 N/Multi-Walled Carbon Nanotubes Composite Toward Ultra-Stable and Ultralow-Temperature Proton Batteries.

Benefiting from the proton's small size and ultrahigh mobility in water, aqueous proton batteries are regarded as an attractive candidate for high-power and ultralow-temperature energy storage devices. Herein, a new-type C4 N polymer with uniform micropores and a large specific surface area is prepared by sulfuric acid-catalyzed ketone amine condensation reaction and employed as the electrode of proton batteries. Multi-walled carbon nanotubes (MWCNT) are introduced to induce the in situ growth of C4 N, and reaped significantly enhanced porosity and conductivity, and thus better both room- and low-temperature performance. When coupled with MnO2 @Carbon fiber (MnO2 @CF) cathode, MnO2 @CF//C4 N-50% MWCNT full battery shows unprecedented cycle stability with a capacity retention of 98% after 11 000 cycles at 10 A g-1 and even 100% after 70 000 cycles at 20 A g-1 . Additionally, a novel anti-freezing electrolyte (5 m H2 SO4  + 0.5 m MnSO4 ) is developed and showed a high ionic conductivity of 123.2 mS cm-1 at -70 °C. The resultant MnO2 @CF//C4 N-50% MWCNT battery delivers a specific capacity of 110.5 mAh g-1 even at -70 °C at 1 A g-1 , the highest in all reported proton batteries under the same conditions. This work is expected to offer a package solution for constructing high-performance ultralow-temperature aqueous proton batteries.