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OBJECTIVES: This study aims to develop a robust predictive model for survival in AML patients undergoing allo-HSCT. METHODS: It was performed a retrospective analysis of 336 AML patients who underwent allo-HSCT at Peking University First Hospital between September 2003 and March 2023. Univariable and multivariable Cox regression analyses were conducted to determine hazard ratios (HR) for overall survival. A predictive model was developed based on multivariable analysis results. Internal validation was carried out through bootstrap resampling, and the model's performance was assessed using the Concordance Index (C-index), Receiver Operating Characteristics (ROC) curve, calibration plots, and Decision Curve Analysis (DCA). RESULTS: Our prognostic model, which includes age, disease stage, donor/recipient gender, mononuclear cell counts, and the Hematopoietic Cell Transplantation Comorbidity Index (HCT-CI), effectively stratified patients into low-risk and high-risk groups. The two groups showed significant differences in overall survival (P<0.0001), disease-free survival (P<0.0001), non-relapse mortality (NRM) (P<0.0001), and relapse rates (P=0.08). The model achieved a C-index of 0.71. Calibration plots and DCA confirmed strong alignment between predicted and observed outcomes. Subgroup analysis revealed that overall survival was significantly lower in the high-risk group compared to the low-risk group in both measurable residual disease (MRD) negative and MRD positive subgroups (P=0.015 for both). CONCLUSION: The developed prognostic model, which integrates comprehensive disease and patient characteristics, enhances risk stratification for AML patients undergoing allo-HSCT. This model effectively stratifies risk in both MRD-negative and MRD-positive subgroups and may facilitate more informed MRD-based treatment decisions.

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Background: The homologous recombination deficiency (HRD) score serves as a promising biomarker to identify patients who are eligible for treatment with PARP inhibitors (PARPi). Previous studies have suggested a 3-biomarker Genomic Instability Score (GIS) threshold of ≥ 42 as a valid biomarker to predict response to PARPi in patients with ovarian cancer and breast cancer. However, the GIS threshold for prostate cancer (PCa) is still lacking. Here, we conducted an exploratory analysis to investigate an appropriate HRD score threshold and to evaluate its ability to predict response to PARPi in PCa patients. Methods: A total of 181 patients with metastatic castration-resistant PCa were included in this study. Tumor tissue specimens were collected for targeted next-generation sequencing for homologous recombination repair (HRR) genes and copy number variation (CNV) analysis. The HRD score was calculated based on over 50,000 single-nucleotide polymorphisms (SNP) distributed across the human genome, incorporating three SNP-based assays: loss of heterozygosity, telomeric allelic imbalance, and large-scale state transition. The HRD score threshold was set at the last 5th percentile of the HRD scores in our cohort of known HRR-deficient tumors. The relationship between the HRD score and the efficacy in 16 patients of our cohort who received PARPi treatment were retrospectively analyzed. Results: Genomic testing was succeeded in 162 patients. In our cohort, 61 patients (37.7%) had HRR mutations (HRRm). BRCA mutations occurred in 15 patients (9.3%). The median HRD score was 4 (ranged from 0 to 57) in the total cohort, which is much lower than that in breast and ovarian cancers. Patients who harbored HRRm and BRCA or TP53 mutations had higher HRD scores. CNV occured more frequently in patients with HRRm. The last 5th percentile of HRD scores was 43 in the HRR-mutant cohort and consequently HRD high was defined as HRD scores ≥ 43. In the 16 patients who received PARPi in our cohort, 4 patients with a high HRD score achieved an objective response rate (ORR) of 100% while 12 patients with a low HRD score achieved an ORR of 8.3%. Progression-free survival (PFS) in HRD high patients was longer compared to HRD low patients, regardless of HRRm. Conclusions: A HRD score threshold of 43 was established and preliminarily validated to predict the efficacy of PARPi in this study. Future studies are needed to further verify this threshold.

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Objective: Previous studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC). Methods: Duration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC. Results: Compared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus. Conclusion: Overall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.

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To compare the impact of two pesticide dose forms on Blattella germanica (B. germanica)resistance enzymes.The micro-drop technique was utilized on subcultured B. germanica, and the metabolic enzyme activity was assessed.Using spectrophotometry, the relative enzyme activities of B.germanica were determined.Profile analysis was used to compare the enzyme activities of beta-cypermethrin in both nanoemulsion and traditional emulsion forms.Findings: The suppression percentages of the acetylcholinesterase enzyme (AchE), GST, and P450-O demethylases across different pesticide formulations were analyzed using regression equations, yielding F = 31.18, P < 0.001; F = 9.18, P < 0.001; and F = 4.58, P < 0.02.Conclusion: The suppression of AchE, GST, and P450-O demethylase by beta-cypermethrin nanoemulsion was more significant compared to the beta-cypermethrin emulsifiable concentrate.The study concluded that beta-cypermethrin nanoemulsion had a significant impact on insect detoxifying enzymes compared to beta-cypermethrin emulsifiable concentrate due to their numerous advantages.

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Separation of racemic drugs is of great importance and interest in chemistry and pharmacology. Here, we report the bottom-up synthesis of the binaphthyl-based chiral covalent organic frameworks (CCOFs), (R)-BHTP-COF. Then, high-performance liquid chromatography (HPLC) columns were prepared using (R)-BHTP-COF as a chiral stationary phase (CSP). Racemic ibuprofen was successfully baseline-separated on (R)-BHTP-COF-based CSP, and achieved excellent selectivity (α = 2.32) and chromatographic resolution (Rs = 3.39) factors. Meanwhile, the separation of six racemic drugs by the (R)-BHTP-COF-packed column exhibited high resolution, selectivity, and durability. The successful applications indicate the great potential of CCOFs as a novel stationary phase for efficient HPLC separation.

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The Narasaka-Heck reaction is one of the most straightforward methods for constructing pyrroline derivatives. Herein, we report a novel nickel-catalyzed three-component carbonylation reaction, which cleverly realizes the continuous construction of C(sp3)-N bonds and C(sp3)-C(sp2) bonds and effectively promotes the synthesis of acyl-substituted pyrroline derivatives. Furthermore, this strategy not only expands the conversion pathway of γ,δ-unsaturated oxime esters but also provides a new method for the synthesis of nitrogen-containing heterocyclic compounds.

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Colorectal cancer (CRC) with BRAF V600E mutation presents a formidable scientific and clinical challenge due to its aggressive nature and poor response to standard therapeutic approaches. BRAF V600E mutation-induced conspicuous activation of the MAPK pathway contributes to the relentless tumor progression. Nevertheless, the efficacy of multi-targeted MAPK pathway inhibition remains suboptimal in clinical practice. Patients with high microsatellite instability (MSI-H) have shown favorable results with immune checkpoint inhibitors (ICIs). The combination of the MAPK pathway inhibition with ICIs has recently emerged as a promising regimen to improve clinical outcomes in the microsatellite stable (MSS) subgroup of BRAF V600E-mutant metastatic CRC patients. In this review, we elucidate the unique tumor biology of BRAF V600E-mutant CRC, with a particular focus on the immune features underlying the rationale for ICI treatments in the MSI-H and MSS subpopulations, then highlight the trends in clinical trials of the ICI therapy for BRAF V600E-mutant metastatic CRC.

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According to the diagnostic criteria for HHV-8 (human herpesvirus-8) negative/idiopathic multicentric Castleman disease (iMCD) proposed by Castleman Disease Collaborative Network (CDCN) in 2017, there is a group of HHV-8 negative multicentric Castleman disease (MCD) patients who do not have symptoms and hyperinflammatory state and do not meet the iMCD criteria. This retrospective study enrolled 114 such patients, described as asymptomatic MCD (aMCD), from 26 Chinese centers from 2000-2021. With a median follow-up time of 46.5 months (range: 4-279 months), 6 patients (5.3%) transformed to iMCD. The median time between diagnosis of aMCD and iMCD in these 6 patients was 28.5 months (range: 3-60 months). During follow-up, 7 patients died; three of them died from progression of MCD. Despite that 37.7% patients received systemic treatment targeting MCD, this strategy was neither associated with a lower probability of iMCD transformation nor a lower death rate. The 5-year estimated survival of all aMCD patients was 94.1% (95% CI 88.8-99.6%). Transformation to iMCD was an important predictor of death (log-rank p=0.01) (5-year estimated survival 83.3%). This study suggests that aMCD patients may represent a potential early stage of iMCD, who may not require immediate treatment but should be closely monitored.

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Photothermal therapy (PTT) shows promise in cancer treatments due to its good spatiotemporal selectivity and minimal invasiveness. However, PTT has some problems such as excessive heat damage to normal tissues, tumor thermo-resistance caused by heat shock proteins (HSPs), and limited efficacy of monotherapy. Here, we construct a patch named "partitioned microneedles" (PMN-SNAP/CuS), which separates the "catalyst" bovine serum albumin-based copper sulfide nanoparticles (CuS@BSA NPs) and the "reactant" S-nitroso-N-acetylpenicillamine (SNAP) into different regions of microneedles, for enhancing mild PTT (mPTT) of melanoma. PMN-SNAP/CuS showed an excellent photothermal effect, Fenton-like catalytic activity, and nitric oxide (NO) generation ability. The combination of NO and reactive oxygen species (ROS) produced by PMN-SNAP/CuS effectively blocked the synthesis of HSPs at the source and enhanced the efficacy of mPTT. Both in vitro and in vivo results proved that PMN-SNAP/CuS significantly enhanced the inhibition of melanoma under 808 nm laser irradiation. In conclusion, our partitioned microneedle strategy based on the combination of enhanced mPTT and gas therapy (GT) provides a promising approach to enhance the therapeutic effect on melanoma.

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2C is a highly conserved picornaviral non-structural protein with ATPase activity and plays a multifunctional role in the viral life cycle as a promising target for anti-picornavirus drug development. While the structure-function of enteroviral 2Cs have been well studied, cardioviral 2Cs remain largely uncharacterized. Here, an endogenous ATP molecule was identified in the crystal structure of 2C from encephalomyocarditis virus (EMCV, Cardiovirus A). The ATP is bound into the ATPase active site with a unique compact conformation. Notably, the γ-phosphate of ATP directly interacts with Arg311 (conserved in cardioviral 2Cs), and its mutation significantly inhibits the ATPase activity. Unexpectedly, this mutation remarkably promotes 2C self-oligomerization and viral replication efficiency. Molecular dynamic simulations showed that the Arg311 side chain is highly dynamic, indicating it may function as a switch between the activation state and the inhibition state of ATPase activity. A hexameric ring model of EMCV 2C full length indicated that the C-terminal helix may get close to the N-terminal amphipathic helices to form a continuous positive region for RNA binding. The RNA-binding studies of EMCV 2C revealed that the RNA length is closely associated with the RNA-binding affinities and indicated that the substrate may wrap around the outer surface of the hexamer. Our studies provide a biochemical framework to guide the characterization of EMCV 2C and the essential role of arginine in cardioviral 2C functions. IMPORTANCE: Encephalomyocarditis virus (Cardiovirus A) is the causative agent of the homonymous disease, which may induce myocarditis, encephalitis, and reproductive disorders in various mammals. 2C protein is functionally indispensable and a promising target for drug development involving broad-spectrum picornaviral inhibitors. Here, an endogenous ATP molecule with a unique conformation was discovered by a combination of protein crystallography and high-performance liquid chromatography in the encephalomyocarditis virus (EMCV) 2C structure. Biochemical and structural characterization analysis of EMCV 2C revealed the critical role of conserved Arg311 in ATPase activity and self-oligomerization of EMCV 2C. The viral replication kinetics and infectivity study suggested that the residue negatively regulated the infectivity titer and virus encapsulation efficiency of EMCV and is, therefore, crucial for 2C protein to promote viral replication. Our systemic structure-function analysis provides unique insights into the function and regulation mechanism of cardioviral 2C protein.

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Regulating the different growth states of polypyrrole (PPy) is a key strategy for obtaining PPy composites with high electromagnetic wave (EMW) absorption properties. This work finds that the growth states of PPy is regulated by controlling the amount of pyrrole added during the preparation of composites, so as to regulate the development of conductive networks to obtain excellent EMW absorption performance. The POP/PPy-200 composite achieves an effective absorption bandwidth (EAB) of 6.24 GHz (11.76-18.00 GHz) at a thickness of only 2.34 mm, covering 100% of the Ku band. The minimum reflection loss of -73.05 dB can be demonstrated at a thickness of only 2.29 mm, while at the same time showing an EAB of 5.96 GHz to meet the requirements of "thin", "light", "wide", and "strong". Such excellent EMW absorption performance is attributed to the conductive loss caused by the regulation of the growth states of PPy and the polarization loss caused by the heterostructure. This work also addresses the key challenge that porous organic polymers (POPs) cannot be applied to EMW absorption due to poor conductivity and providing new insights into the candidates for EMW absorbing materials.

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Background: Recurrent acute myocardial infarction requiring unplanned percutaneous coronary intervention (PCI) is one of the major adverse cardiovascular events (MACEs) in patients with acute coronary syndrome (ACS) after PCI. There is a continuing controversy about the association between serum cystatin C, a biomarker for the evaluation of renal function, and the prognosis of ACS patients following PCI. The retrospective study evaluated the association between serum cystatin C level and MACE in ACS patients after PCI. Methods: Data were retrieved for 330 patients with ACS for primary PCI in a single center. Serum cystatin C levels were measured before PCI. All patients underwent regular follow-ups after PCI, and the studied endpoint was MACE, defined as the need for a repeat revascularization in the heart. The predictive value of serum cystatin C for MACE was analyzed using univariate and multivariate analysis. Restricted cubic spline (RCS) analysis was applied to evaluate the dose-response relationship between serum cystatin C level and MACE in ACS patients following PCI. Results: After a median follow-up of 63 months (range, 1-148 months), 121 of the 330 patients experienced MACE. Compared to patients who did not have MACE, patients who had MACE showed a significant decrease in serum cystatin C levels (0.99±0.32 vs. 1.15±0.78 mg/L, P=0.03). In multivariate regression analysis, serum cystatin C level was an independent risk factor for MACE. According to the serum cystatin C level, patients were divided into 4 categories, Cox regression analysis illustrated that the second quartile of serum cystatin C level indicated an increased risk of MACE in patients with PCI for primary ACS compared to the highest quartile [Q2: adjusted hazard ratio (HR) =2.109; 95% confidence interval (CI): 1.193-3.727; P=0.01]. RCS analysis showed a significant U-shaped dose-response relationship between cystatin C level and MACE in patients with PCI for ACS (P for non-linearity =0.004). Conclusions: These results indicated an association between serum cystatin C level and post-PCI MACE in ACS patients.

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Isobavachin (IBA) is a dihydroflavonoid compound with various pharmacological effects. However, further investigation into the hepatotoxicity of IBA is necessary. This study aims to identify the hepatotoxic effects of IBA and explore its potential mechanisms. The study assessed the impact of IBA on the viability of AML12, HepG2, LO2, rat, and mouse primary hepatocytes using MTT and LDH assays. Autophagy was detected in AML12 cells after IBA treatment using electron microscopy, MDC, and Ad-mCherry-GFP-LC3B fluorescence. The effect of IBA on autophagy-related proteins was examined using Western blot. The results showed that IBA had dose-dependent inhibitory effects on five cells, induced autophagy in AML12 cells, and promoted autophagic flux. The study found that IBA treatment inhibited phosphorylation of PI3K, Akt, and mTOR, while increasing phosphorylation levels of AMPK and ULK1. Treatment with both AMPK and PI3K inhibitors reversed the expression of AMPK and PI3K-Akt-mTOR signaling pathway proteins. These results suggest that IBA may have hepatocytotoxic effects but can also prevent IBA hepatotoxicity by inhibiting the AMPK and PI3K/Akt/mTOR signaling pathways. This provides a theoretical basis for preventing and treating IBA hepatotoxicity in clinical settings.

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Antigen presentation by major histocompatibility complex class I (MHC-I) is crucial for T cell-mediated killing, and aberrant surface MHC-I expression is tightly associated with immune evasion. To address MHC-I downregulation, we conducted a high-throughput flow cytometry screen, identifying bleomycin (BLM) as a potent inducer of cell surface MHC-I expression. BLM-induced MHC-I augmentation rendered tumor cells more susceptible to T cells in coculture assays and enhanced antitumor responses in an adoptive cellular transfer mouse model. Mechanistically, BLM remodeled the tumor immune microenvironment, inducing MHC-I expression in a manner dependent on ataxia-telangiectasia mutated/ataxia telangiectasia and Rad3-related-NF-κB. Furthermore, BLM improved T cell-dependent immunotherapeutic approaches, including bispecific antibody therapy, immune checkpoint therapy, and autologous tumor-infiltrating lymphocyte therapy. Importantly, low-dose BLM treatment in mouse models amplified the antitumor effect of immunotherapy without detectable pulmonary toxicity. In summary, our findings repurpose BLM as a potential inducer of MHC-I, enhancing its expression to improve the efficacy of T cell-based immunotherapy.

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RATIONALE: This study reports the first case of congenital hypothyroidism (CH) and alpha thalassemia in a child in China, with anemia and muscle damage as the main manifestations. Analyzing and studying this case is of great significance in reducing missed and misdiagnosed CH and will provide a clinical strategy for treating these patients. PATIENT CONCERNS: Child, female, 2 years and 7 months old, the child appeared dispirited, had poor appetite, shallow complexion, reduced activities with anemia, elevated muscle enzymes, height, and growth retardation. DIAGNOSES: The child was diagnosed with CH with alpha thalassemia. INTERVENTIONS: The patient was treated with levothyroxine sodium and anemia correction. OUTCOMES: The children's current spirit, appetite, red face, normal limb activity, physical development, and intelligence were significantly better than those of normal children of the same age. CONCLUSIONS: CH with alpha thalassemia, especially anemia and muscle damage as the main manifestations, has not been reported. Administration of levothyroxine sodium is effective in correcting anemia in patients with CH and alpha thalassemia. LESSON: Due to CH and alpha thalassemia, there are no specific symptoms and they are prone to missed diagnosis and misdiagnosis. Therefore, patients with anemia and elevated muscle enzyme levels should be routinely tested for thyroid function to diagnose them early and provide proper treatment to avoid negative consequences.

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Previous findings have indicated the potential benefits of the Chinese traditional medicine Qiliqiangxin (QLQX) in heart failure. Here we performed a double-blind, randomized controlled trial to evaluate the efficacy and safety of QLQX in patients with heart failure and reduced ejection fraction (HFrEF). This multicenter trial, conducted in 133 hospitals in China, enrolled 3,110 patients with HFrEF with NT-proBNP levels of ≥450 pg ml-1 and left ventricular ejection fraction of ≤40%. Participants were randomized to receive either QLQX capsules or placebo (four capsules three times daily) alongside standard heart failure therapy. The trial met its primary outcome, which was a composite of hospitalization for heart failure and cardiovascular death: over a median follow-up of 18.3 months, the primary outcome occurred in 389 patients (25.02%) in the QLQX group and 467 patients (30.03%) in the placebo group (hazard ratio (HR), 0.78; 95% confidence interval (CI), 0.68-0.90; P < 0.001). In an analysis of secondary outcomes, the QLQX group showed reductions in both hospitalization for heart failure (15.63% versus 19.16%; HR, 0.76; 95% CI, 0.64-0.90; P = 0.002) and cardiovascular death (13.31% versus 15.95%; HR, 0.83; 95% CI, 0.68-0.996; P = 0.045) compared to the placebo group. All-cause mortality did not differ significantly between the two groups (HR, 0.84; 95% CI, 0.70-1.01; P = 0.058) and adverse events were also comparable between the groups. The results of this trial indicate that QLQX may improve clinical outcomes in patients with HFrEF when added to conventional therapy. ChiCTR registration: ChiCTR1900021929 .

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Poisonous histamine is accumulated in stale meat and fermented foods. The rapid and stable detection of histamine is essential for food safety. Herein, a ratiometric fluorometric method for histamine detection was designed through in situ preparing double-stranded DNA­copper nanoclusters (dsDNA-Cu NCs) stained with 4',6-diamidino-2-phenylindole (DAPI). dsDNA-Cu NCs with red emission were rapidly synthesized via mixing Cu2+, ascorbate and dsDNA at room temperature for 5 min. When DAPI was added during preparation, DAPI coordinated with the Cu element accompanied by the quenched red emission of dsDNA-Cu NCs, and DAPI bound to dsDNA together with the enhanced blue emission of DAPI. Upon adding DAPI and histamine simultaneously, the coordination of histamine with the Cu element further decreased the red emission of dsDNA-Cu NCs, and drove the movement of DAPI from the Cu element to dsDNA along with the enhanced blue emission of DAPI. Significantly, ratiometric fluorescence was insensitive to variations in instrument and environment, causing stable measurement. Meanwhile, in situ synthesis integrated probe preparation with analyte detection, reducing time consumption. Additionally, this method quantified histamine in the concentration range of 7-50 µM with a detection limit of 3.6 µM. It was applied to determining histamine in food with satisfactory accuracy and precision.

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Widespread glyphosate contamination in the environment and its endocrine-disrupting potential are concerning. However, evidence of glyphosate's effects on glycemic health is limited. To examine the association between glyphosate and glucose homeostasis in the general US population, a total of 3038 individuals were enrolled from the 2013-2016 cycles of the National Health and Nutrition Examination Survey (NHANES). Survey-weighted linear regression and restricted cubic spline curves were used to detect the associations between glyphosate and glycemic disorders. The effects of interactions between sex hormones and glyphosate on glycemic outcomes were evaluated. The results showed that glyphosate was significantly linked to increased glycated hemoglobin A1c (HbA1c) levels (ß = 0.01; 95%CI, 0.01 to 0.02; p = 0.001) and the compromised homeostatic model assessment of beta-cell function (HOMA-beta) scores (ß = -0.09; 95%CI, -0.17 to -0.01; p = 0.024). More importantly, these "glyphosate-glycemic disorder" associations were significantly modified by sex hormone-binding globulin (SHBG; P for interaction < 0.05), with more pronounced relationships being identified in individuals with low SHBG levels. Our findings indicate that glyphosate is correlated with glucose dyshomeostasis. Individuals with low SHBG levels exhibited susceptibility to glyphosate-related glycemic toxicity; therefore, it might be prudent to determine glycemic health in those subjects with glyphosate exposure.

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Human-machine interactions (HMIs) have penetrated into various academic and industrial fields, such as robotics, virtual reality, and wearable electronics. However, the practical application of most human-machine interfaces faces notable obstacles due to their complex structure and materials, high power consumption, limited effective skin adhesion, and high cost. Herein, we report a self-powered, skin adhesive, and flexible human-machine interface based on a triboelectric nanogenerator (SSFHMI). Characterized by its simple structure and low cost, the SSFHMI can easily convert touch stimuli into a stable electrical signal at the trigger pressure from a finger touch, without requiring an external power supply. A skeleton spacer has been specially designed in order to increase the stability and homogeneity of the output signals of each TENG unit and prevent crosstalk between them. Moreover, we constructed a hydrogel adhesive interface with skin-adhesive properties to adapt to easy wear on complex human body surfaces. By integrating the SSFHMI with a microcontroller, a programmable touch operation platform has been constructed that is capable of multiple interactions. These include medical calling, music media playback, security unlocking, and electronic piano playing. This self-powered, cost-effective SSFHMI holds potential relevance for the next generation of highly integrated and sustainable portable smart electronic products and applications.