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Ovarian cancer is the leading cause of death among all gynecological malignancies, and drug resistance renders the current chemotherapy agents ineffective for patients with advanced metastatic tumors. We report an effective treatment strategy for targeting metastatic ovarian cancer involving a nanoformulation (Bola/IM)─bola-amphiphilic dendrimer (Bola)-encapsulated imatinib (IM)─to target the critical mediator of ovarian cancer stem cells (CSCs) CD117 (c-Kit). Bola/IM offered significantly more effective targeting of CSCs compared to IM alone, through a novel and tumor-specific β-catenin/HRP2 axis, allowing potent inhibition of cancer cell survival, stemness, and metastasis in metastatic and drug-resistant ovarian cancer cells. Promising results were also obtained in clinically relevant patient-derived ascites and organoids alongside high tumor-oriented accumulation and favorable pharmacokinetic properties in mouse models. Furthermore, Bola/IM displayed synergistic anticancer activity when combined with the first-line chemotherapeutic drug cisplatin in patient-derived xenograft mouse models without any adverse effects. Our findings support the use of Bola/IM as a nanoformulation to empower IM, providing targeted and potent treatment of metastatic ovarian cancer. Our study thus represents a significant advancement toward addressing the unmet medical need for improved therapies targeting this challenging disease.

Increasing landslide activities in cold regions have been attributed to rising temperatures and consequent permafrost degradation. While previous studies have linked permafrost degradation to slope instability, the elevation-dependent effects of this degradation on landslide occurrences in the high-mountain regions of the Qinghai–Tibet Plateau (QTP) remain poorly understood, particularly concerning their spatial distribution and timing. This study addresses this gap by investigating the distribution and timing of landslides in the Babao River catchment, located in the southeastern Qilian Mountains of the northeastern QTP. Our results reveal a substantial increase in landslide events during the study period of 2009–2018: only 14 occurrences were recorded before and in 2009, 22 between 2010 and 2015, and 105 during 2016–2018. Notably, we observed an upward shift in the elevation of landslide occurrences, with an average increase of approximately 130 m over the ten-year period. Analysis of annual permafrost distribution maps indicates that this shift coincides with the rising lower altitudinal limit of mountain permafrost in the study area, likely driven by increased temperatures and precipitation. These findings highlight the critical role of elevation-dependent processes in influencing landslide dynamics under changing climatic conditions, particularly the transition from undisturbed permafrost to seasonally frozen ground at higher elevations. This study provides valuable insights for disaster prevention and mitigation in high-altitude regions, emphasizing the heightened risks posed by permafrost degradation under ongoing warmer and wetter climatic conditions.

Byline: Jisheng. Li, Liping. Zhu, Justin. Stebbing, Ling. Peng Classical activating alterations including exon 19 deletions and exon 21 L858R point mutations comprise the majority of epidermal growth factor receptor [...]

The phase relations of the R2Fe14B–Ce2Fe14B (R= Nd, Pr) pseudobinary systems have been investigated by using X-ray powder diffraction, scanning electron microscopy equipped with energy dispersive X-ray spectroscopy and differential thermal analysis. The X-ray powder diffraction results show that continuous solid solutions were formed in this R2Fe14B–Ce2Fe14B (R= Nd, Pr) pseudobinary systems, and all (R,Ce)2Fe14B solid solutions belong to the tetragonal structure with space group P42/mnm. With the increase in Ce content, the lattice parameters a, c, the peritectic reaction temperatures of the (R, Ce)2Fe14B (R= Nd, Pr) solid solutions decrease linearly, and the cell volume Vvaries in the form of the regression line. Based on the X-ray powder diffraction results and differential thermal analysis data, the quasi-binary phase diagrams of the R2Fe14B–Ce2Fe14B (R= Nd, Pr) systems have been established.

Byline: Jisheng. Li, Hejiang. Yu, Ling. Peng, Li. Li, Xiangling. Wang, Jing. Hao, Na. Shao Background: Small-cell carcinoma is a relatively infrequent pathological variety of esophageal cancer. In this study, [...]

With the development of artificial intelligence and information technology, drones working in tandem with manned aerial vehicle have become the new normal. Current paper focuses on the following theme: how to assess the effectiveness of manned/unmanned aerial vehicle systems under different formations. However, the analysis of the effectiveness of manned/unmanned aircraft cooperation faces the problem of unclear mechanisms and difficulty in tracing the key influencing factors. Therefore, in this paper, a closed frequent pattern mining method is used to analyze and design a new data structure based on cross-linked table improvement. In this paper, the units and capabilities in the manned/unmanned aerial vehicle system are mined and analyzed in a time-series manner to obtain the effectiveness of the patterns of manned/unmanned aircraft utilization in tandem under different formations. Finally, a typical maritime application scenario is used as an example to effectively compare the effectiveness of different manned/unmanned aircraft cooperative modes and to provide guidance for the subsequent development of manned/unmanned aircraft cooperative applications.

The phase relations of the Fe–Pt–Ho ternary system at 500 °C have been studied by using X-ray diffraction, scanning electron microscopy and energy dispersive spectroscopy techniques. The Ho3Pt4phase is stable at 500 °C, and the introduction of Fe does not cause the Ho3Pt4phase to be decomposed into the two neighbouring phases HoPt and HoPt2. The single phase ranges of α-Fe, Fe3Pt, FePt, FePt3and Pt in Fe–Pt binary system are from 0 to 10 at.% Pt, 14 to 32 at.% Pt, 33 to 63 at.% Pt, 66 to 78 at.% Pt, and 82 to 100 at.% Pt, respectively. The highest solid solubility of Ho in the α-Fe, Fe3Pt, FePt, FePt3and (Pt, Fe) phases is less than 1.5 at.% Ho, 2 at.% Ho, 2 at.% Ho, 1.5 at.% Ho and 1.5 at.% Ho, respectively. The isothermal section at 500 °C of the Fe–Pt–Ho ternary alloy phase diagram has been constructed, which consists of 19 single-phase regions, 35 two-phase regions and 17 three-phase regions. No new ternary compounds were found.

The current greedy iterative pursuit algorithms for sparse channel estimation in an orthogonal frequency division multiplexing (OFDM) system based on compressive sensing (CS) or distributed CS (DCS) have the disadvantages of relying on channel priori information as halting condition and having a low support searching efficiency. Under DCS framework, this letter proposes a unique halting condition for greedy algorithms by exploiting the delay correlation between adjacent symbol channels. Additionally, we present a segmented pruning strategy that supports to select multiple atoms in a single iteration to improve the support searching efficiency. Simulation results show that our algorithm can achieve more robust sparsity-adaptive channel estimation with reduced computational complexity compared to the traditional methods.

Two‐coordinate Carbene−Metal−Amide (CMA) complexes with thermally activated delayed fluorescence (TADF) have attracted much attention owing to their excellent luminescence properties and potential applications in organic light‐emitting devices. However, the luminescence mechanism remains unclear. Herein, we took one CMA Au(I) complex as an example and investigate its relevant photophysics using both density functional theory (DFT) and time‐dependent DFT methods with a polarizable continuum model. The calculated absorption and emission spectra agree with the experimental data and the S1and T1states show mixed ligand to ligand charge transfer (CT) and ligand to metal CT characters. Small spatial overlap between the highest occupied molecular orbital (HOMO) and the lowest unoccupied molecular orbital (LUMO) minimizes the energy difference between the S1and T1states (ΔEST). Properly large spin‐orbit coupling promotes the reverse intersystem crossing (rISC) process. At 300 K, the rISC process is much more efficient than the T1phosphorescent emission, which leads to the TADF emission. The initially populated S1state first hops to the T1state via intersystem crossing (ISC). At 300 K, the reverse ISC (rISC) process from T1to S1is much more efficient than the T1phosphorescence emission enabling thermally activated delayed fluorescence. Small energy gap between S1and T1, proper spin‐orbit coupling value, and certain thermal energy facilitate rISC.

Cancer adhesion to the mesothelium is critical for peritoneal metastasis, but how metastatic cells adapt to the biomechanical microenvironment remains unclear. Our study demonstrates that highly metastatic (HM), but not non-metastatic, ovarian cancer cells selectively activate the peritoneal mesothelium. HM cells exert a stronger adhesive force on mesothelial cells via P-cadherin, an adhesion molecule abundant in late-stage tumors. Mechanical activation of P-cadherin enhances lipogenic gene expression and lipid content in HM cells through SREBP1. P-cadherin also induces glycolysis in the interacting mesothelium without affecting lipogenic activity, with the resulting lactate serving as a substrate for lipogenesis in HM cells. Nanodelivery of small interfering RNA (siRNA) targeting P-cadherin or MCT1/4 transporters significantly suppresses metastasis in mice. Moreover, increased fatty acid synthase levels in metastatic patient samples correlate with high P-cadherin expression, supporting enhanced de novolipogenesis in the metastatic niche. This study reveals P-cadherin-mediated mechano-metabolic coupling as a promising target to restrain metastasis.

The catalytic transformation of N2to NH3by transition metal complexes is of great interest and importance but has remained a challenge to date. Despite the essential role of vanadium in biological N2fixation, well-defined vanadium complexes that can catalyze the conversion of N2to NH3are scarce. In particular, a V(NxHy) intermediate derived from proton/electron transfer reactions of coordinated N2remains unknown. Here, we report a dinitrogen-bridged divanadium complex bearing POCOP (2,6-(tBu2PO)2-C6H3) pincer and aryloxy ligands, which can serve as a catalyst for the reduction of N2to NH3and N2H4. Low-temperature protonation and reduction of the dinitrogen complex afforded the first structurally characterized neutral metal hydrazido(2−) species ([V]═NNH2), which mediated 15N2conversion to 15NH3, indicating that it is a plausible intermediate of the catalysis. DFT calculations showed that the vanadium hydrazido complex [V]═NNH2possessed a N–H bond dissociation free energy (BDFEN–H) of as high as 59.1 kcal/mol. The protonation of a vanadium amide complex ([V]–NH2) with [Ph2NH2][OTf] resulted in the release of NH3and the formation of a vanadium triflate complex, which upon reduction under N2afforded the vanadium dinitrogen complex. These transformations model the final steps of a vanadium-catalyzed N2reduction cycle. Both experimental and theoretical studies suggest that the catalytic reaction may proceed via a distal pathway to liberate NH3. These findings provide unprecedented insights into the mechanism of N2reduction related to FeV nitrogenase.

With the alarming and prevailing antimicrobial resistance (AMR) comes an urgent need for novel antimicrobial agents that are not only effective and robust but also do not induce resistance development. Amphiphilic dendrimers are emerging as a promising new paradigm to combat bacterial AMR. They can mimic antimicrobial peptides to produce potent antibacterial activity yet with a low likelihood of generating resistance. In addition, they are stable against enzymatic degradation thanks to their unique dendritic architecture. Importantly, these amphiphilic dendrimers are composed of distinct hydrophobic and hydrophilic entities bearing dendritic structures, which can be precisely designed and synthesized to optimize the hydrophobic–hydrophilic balance yielding potent antibacterial activity while minimizing adverse effects and drug resistance. In this short review, we present the challenges and current state of research in developing amphiphilic dendrimers as new antibiotic substitutes. We start with a brief overview of the advantages and opportunities associated with using amphiphilic dendrimers to combat bacterial AMR. We then outline the specific considerations and the mechanisms underlying the antibacterial activity of amphiphilic dendrimers. We focus on the importance of the amphiphilic nature of a dendrimer that balances hydrophobicity and hydrophilicity viagauging the hydrophobic entity and the dendrimer generation, branching unit, terminal group and charge to allow high antibacterial potency and selectivity while minimizing toxicity. Finally, we present the future challenges and perspectives for amphiphilic dendrimers as antibacterial candidates for combating AMR.

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1540-5885.2010.00745.x Byline: Ling Peng (1), Adam Finn (2) Abstract: The product development literature has identified several individual characteristics that could influence how subjects respond to new products in concept tests. Few of these characteristics have been thoroughly investigated. The purpose of this research is to examine whether a number of personality traits (1) do influence concept evaluation scores and (2) can be used to identify respondents who provide substantially higher-quality data in concept testing and whether the answers to these questions change for major versus minor innovations. The data quality of the concept testing data is defined using the generalizability theory, which provides a decision-specific G-coefficient. Higher quality means a G-coefficient closer to 1 for a particular managerial decision. A Web-based study to concept test 10 appliance innovations on multiple occasions was conducted among 105 panelists from the Institute for Online Consumer Studies (IOCS). During the concept testing, respondents' innovativeness, change-seeking tendency, and propensity to exert cognitive effort were also measured. The results showed that the respondent characteristics influence the mean evaluation of the concepts and the psychometric quality of the concept testing data: (1) there is a significant linear relationship between concept scores and all of the innovativeness scales and change-seeking measures; (2) the effect of innovativeness on concept testing outcomes is even more substantial for major innovations than for minor innovations; (3) the study provides evidence that the quality of concept testing data provided by respondents varies substantially with their innovativeness, whereas the differences are more modest when scaling just minor innovations; (5) there are also strong effects on data quality for the Need to Evaluate scale used to capture cognitive effort characteristics; and (6) there is little effect of segmenting on social desirability on data quality. Managerially, the current results indicate that a product manager wanting to concept test a pool of appliance concepts can benefit from screening for the respondents who will provide higher-quality concept testing data. For example, respondents who are high on domain-specific innovativeness provide the highest-quality concept testing data for both minor and major innovations. The effects of traits are stronger for major innovations, supporting the claim that subject selection is a more critical issue in concept testing of major innovations. Product managers can improve the quality of their concept testing data without an increase in cost by screening the subjects they use in concept testing. Author Affiliation: (1)Lingnan University of Hong Kong (2)University of Alberta School of Business Article note: Address correspondence to: Ling Peng, Department of Marketing and International Business, Lingnan University School of Business, Tuen Mun, Hong Kong. Tel.: 852-2616-8242. Fax: 852-2467-3049. E-mail: L2peng@ln.edu.hk.

To authenticate to the full-text of this article, please visit this link: http://dx.doi.org/10.1111/j.1540-5885.2010.00712.x Byline: Ling Peng (1), Adam Finn (2) Abstract: Although traditional and conjoint forms of concept testing play an important role in the new product development process, they largely ignore data quality issues, as evidenced by the traditional reliance on the percent Top-2-Box scores heuristic. The purpose of this research is to reconsider the design of concept testing from a measurement theory (generalizability theory) perspective and to use it to suggest some ways to improve the psychometric quality of concept testing. Generalizability theory is employed because it can account for the multiple facets of variation in concept testing, and it enables a concept test to be designed to provide a required level of accuracy for decision making in the most effective way, whether the purpose of measurement is to scale concepts or something else, such as to scale respondents. The paper identifies four types of sources-concept-related factors, response task factors, situational factors, and respondent factors-that can contribute to the observed variation in concept testing and develops six research propositions that summarize what is known or assumed about their contribution to observed score variance. Four secondary data sets from different concept testing contexts are then used to test the propositions. The results provide new insights into the design of concept tests and the psychometric quality of the concept testing data: (1) the concepts facet is not a major contributor to response variation; (2) of the response task factors, concept formulations are a trivial source of variance, but items are not always a trivial source of variance; (3) the situational factors that are investigated are trivial sources of variance; (4) respondents are always a major contributor to the total variation; (5) concepts by respondents are not always a major contributor and the other interactions are often not trivial; and (6) residual error is always a major source of variance. Additionally, the analyses of the secondary data sets enable some useful managerial conclusions to be drawn about the design of concept testing. First, the sample size needed to reliably scale concepts depends on the types of concepts being tested. Second, averaging over items provides considerably more reliable information than relying on a single item. Third, which specific item performs best is inconsistent and very context specific. The popular purchase intention item is never the best single item to use. Fourth, not much is gained by sampling levels of the response task factors. Finally, concept testing should be designed to meet the needs of specific managerial tasks. Author Affiliation: (1)Lingnan University of Hong Kong (2)University of Alberta School of Business Article note: Address correspondence to: Ling Peng, Department of Marketing and International Business, Lingnan University School of Business, Tuen Mun, Hong Kong. Tel.: 852-2616-8242. Fax: 852-2467-3049. E-mail: L2peng@ln.edu.hk.

Alternative splicing (AS) is a gene regulatory mechanism that drives protein diversity and dysregulation of AS plays a significant role in tumorigenesis. This study aimed to develop a prognostic signature based on AS and elucidate the role in tumor immune microenvironment (TIME) in clear cell renal cell carcinoma (ccRCC). The prognosis-related AS events were analyzed by univariate Cox regression analysis. Gene set enrichment analyses (GSEA) were performed for functional annotation. Prognostic signatures were identified and validated using univariate and multivariate Cox regression, LASSO regression, Kaplan–Meier survival analysis, and proportional hazards model. The context of TIME in ccRCC was also analyzed. Gene and protein expression data of C4orf19 were obtained from ONCOMINE website and Human Protein Altas. Splicing factors (SFs) regulatory networks were visualized. 4431 survival-related AS events in ccRCC were screened. Based on splicing subtypes, eight AS prognostic signatures were constructed. A nomogram with good prognostic prediction was generated. Furthermore, the prognostic signatures were significantly correlated with TIME diversity and immune checkpoint inhibitor (ICI)-related genes. C4orf19 was the only gene whose expression levels were downregulated among the prognostic AS-related genes, which is considered as a promising prognostic factor in ccRCC. Potential functions of SFs were determined by splicing regulatory networks. In our study, AS patterns of novel indicators for prognostic prediction of ccRCC were explored. The AS-SF networks provide information of regulatory mechanisms. Players of AS events related to TIME were investigated, which contribute to prognosis monitoring of ccRCC.

Enhancing Autonomous Decision-Making (ADM) for unmanned combat aerial vehicle formations in beyond-visual-range air combat is pivotal for future battlefields, whereas the predominant reinforcement learning technique for ADM has been proven to be inadequately fitting complex tactical Unit Coordination (UC), limiting the integrity of decision-making for formations. This study proposes a knowledge-enhanced ADM method, with a focus on UC, to elevate formation combat effectiveness. The main innovation is integrating data mining technique with tactical knowledge mining and integration. Foremost, based on Frequent Event Arrangement Mining (FEAM) theory, a cross-channel UC knowledge mining method is designed by introducing data flow, which is capable of capturing dynamic coordinative action sequences. Then, a dual-mode knowledge integration method is proposed by employing the Graph Attention Network (GAT) and attenuated structural similarity, bolstering the interplay between autonomous UC tactics fitting and knowledge injection. The experimental results demonstrate that the algorithm surpasses the existing methods, providing more strategic maneuver trajectories and a win rate of more than 90% in different scenarios. The method is promising to augment the autonomous operational capabilities of unmanned formations and drive the evolution of combat effectiveness.

In this paper, an N-type Lateral Diffused Metal Oxide Semiconductor (LDMOS) device was designed using a heavily doped P+ well and drain N-type buffer layer structure in the BCD process. The hardened mechanism of heavily doped P+ well and drain N-type buffer layer structures was simulated and analyzed using a TCAD device simulator. To verify the anti-SEE performance of the LDMOS, the irradiation test was conducted using Ta ion (LET = 79.2 MeV·cm−2mg−1). The results show that increasing P+ well doping concentration and using buffer layer structure can increase the single event burnout (SEB) voltage of high-voltage LDMOS devices. SEB did not occur within the full operation voltage range.

A deeper understanding of the interaction between tumor cell and the immune microenvironment in bladder cancer may help select predictive and prognostic biomarkers. The current study aims to construct a prognostic signature for bladder cancer by analysis of molecular characteristics, as well as tumor-immune interactions. RNA-sequencing and clinical information from bladder cancer patients were downloaded from the TCGA database. The single sample Gene Sets Enrichment Analysis (ssGSEA) and Cell type Identification by Estimating Relative Subsets of RNA Transcripts (CIBERSORT) were employed to separate the samples into two clusters. Lasso Cox regression was performed to construct an immune gene signature for bladder cancer. The correlation between key target genes of immune checkpoint blockade and the prognostic signature was also analyzed. Dataset from Gene Expression Omnibus (GEO) was retrieved for validation. Two immunophenotypes and immunological characteristics were identified, and a 17-immune gene signature was constructed to provide an independent prognostic signature for bladder cancer. The signature was verified through external validation and correlated with genomic characteristics and clinicopathologic features. Finally, a nomogram was generated from the clinical characteristics and immune signature. Our study reveals a tumor-immune microenvironment signature useful for prognosis in bladder cancer. The results provide information on the potential development of treatment strategies for bladder cancer patients. Prospective studies are warranted to validate the prognostic capability of this model, but these data highlight the role of the microenvironment in the clinical outcome of patients.

Allergic rhinitis (AR) is a chronic inflammatory disease of the nasal mucosa. M2 macrophage polarization can reduce inflammation and repair tissue injury during AR development. Studies have substantiated the involvement of miRNAs in AR pathogenesis. Herein, the molecular mechanism of miR‐214‐3p in AR development was explored. To mimic the AR environment, ovalbumin (OVA) was used to treat macrophages. MiR‐214‐3p and glycogen synthase kinase 3 beta (GSK3B) expression in nasal mucus tissues and macrophages was assessed by RT‐qPCR. The M2 phenotypic signature of CD206 in macrophages was assessed by flow cytometry. The protein expression of GSK3B and M2 macrophage markers (ARG‐1 and IL‐10) was evaluated by western blotting. The correlation between miR‐214‐3p and GSK3B was validated by a luciferase reporter assay. We found that miR‐214‐3p was overexpressed in macrophages and nasal mucus tissues from AR patients. MiR‐214‐3p facilitated M2 polarization of macrophages upon OVA stimulation. Mechanistically, miR‐214‐3p targeted the GSK3B 3′ untranslated region in macrophages. In addition, GSK3B was downregulated in macrophages and nasal mucus tissues from AR patients. In rescue assays, GSK3B downregulation reversed the inhibitory effects of miR‐214‐3p silencing on M2 polarization of macrophages treated with OVA. Overall, miR‐214‐3p facilitates M2 macrophage polarization by targeting GSK3B.

The role of B cells in the anti-tumor immune response remains controversial. An increase in the number of B cells in the peripheral blood of some tumor patients has been associated with poor immunotherapy efficacy. However, the mechanism leading to the generation of these cells is not well-described. Using a fibrosarcoma model, we show that intraperitoneal administration of a xenogeneic antigen in tumor-bearing mice evokes large increases in antigen-specific serum immunoglobulin formation compared to tumor-naïve mice. An inability of tumor-bearing mice to induce enhanced antibody production after myeloid cell depletion suggests the antibody responses are CD11b+myeloid cell-dependent. In vitro, CD11b+myeloid cells promoted B cell proliferation, activation, and survival. High levels of tumor necrosis factor (TNF)-α were produced by CD11b+cells, and TNF-α blockade inhibited B cell responses. CD11b+cells appear to be important promoters of B cell responses and targeting B cells may increase the efficacy of immunotherapy in tumor-bearing hosts.

M2-tumor associated macrophages (TAMs) play an important role in tumor genesis, progression, and metastasis, and repolarizing M2-TAMs to immune-promoting M1 type is increasingly recognized as a promising strategy against the clinically intractable carcinomas. It is observed that M2 macrophages have a high tropism to the tumor hypoxic area, with their endoplasmic reticulum (ER) stress-associated IRE1-XBP1 pathway activated to inhibit cell glycolysis, promote oxidative phosphorylation (OXPHOS), and facilitate intracellular lipid accumulation, which in turn shapes the typical phenotypes of M2-TAMs, suggesting that manipulating the ER stress response of M2-TAMs might stand as a breakthrough for antitumor therapy. However, current attempts to repolarize M2 cells remain limited and are greatly challenged by the hypoxic nature of tumors. Also, the high level of reactive oxygen species (ROS) in the tumor microenvironment (TME) is favorable for the polarization of M2-TAMs. Here, we encapsulated KIRA6, an inhibitor of the IRE1-XBP1 pathway, into a reductive nanoemulsion containing α-tocopherol. Our α-T-K had dual inhibitory effects on the ER stress and oxidative stress. Both in vitroand in vivoexperiments suggested that α-T-K effectively reprogrammed M2 macrophages even under hypoxia, achieved by increasing glycolysis and suppressing fatty acid oxidation (FAO). In addition, our data revealed that α-T-K not only delayed tumor growth but elevated the curative effect of PD-1 antibody. Our research demonstrated that simultaneous inhibition of ER stress and oxidative stress could effectively repolarize M2-TAMs under hypoxia, which not only filled the current gap in regulating the biological repolarization of macrophages under hypoxia but provided a meaningful reference for the clinical immunotherapy of sensitized anti-PD-1.

Pancreatic ductal adenocarcinoma (PDAC) is a deadly cancer with no efficacious treatment. The application of nanomedicine is expected to bring new hope to PDAC treatment. In this study, we report a novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin, which demonstrated potent anticancer activity, markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from PDAC patients. This dendrimer nanodrug was constructed with a fluorinated amphiphilic dendrimer, which self-assembled into micelles nanostructure and encapsulated doxorubicin with high loading. Because of the fine nanosize, stable formulation and acid-promoted drug release, this dendrimeric nanosystem effectively accumulated in tumor, with deep penetration in tumor tissue and rapid drug uptake/release profile in cells, ultimately resulting in potent anticancer activity and complete suppression of tumor growth in patient-derived xenografts. Most importantly, this dendrimer nanodrug generated uniform and effective response when treating 35 primary pancreatic cancer cell lines issued from patient samples as a robust platform for preclinical drug efficacy testing. In addition, this dendrimer nanodrug formulation was devoid of adverse effects and showed excellent tolerability. Given all these uniquely advantageous features, this simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC. A novel supramolecular dendrimeric nanosystem carrying the anticancer drug doxorubicin was developed in this study. We demonstrated this nanosystem markedly overcoming the heterogeneity of drug response and resistance of primary cultured tumor cells derived from 35 PDAC patients. This simple and convenient dendrimer nanodrug holds great promise as a potential candidate to treat the deadly PDAC.

Organic smart fluorophores (OSFs) are highly desirable over the past decades because of their potential applications in advanced photonic devices. However, it is still difficult and challenging to obtain such materials with tunable photophysical properties and high emission efficiency based on robust construction strategies. Therefore, we proposed a simple and efficient strategy for constructing OSFs by balancing the competition between intermolecular interactions and external stimuli via molecular structure design. In this work, four pyrene derivatives (T1-Py, T4-Py, T12-Py, and S12-Py) with tunable stimuli-responsive properties were designed and synthesized. The tunable intermolecular interactions in solution states were successfully demonstrated by the molecular structure and solution concentration-dependent luminescence properties. The effect of alkyl chain length on molecular packing in solid states was investigated by polarized optical microscopy and powder and single-crystal X-ray diffraction; the results show that with the increase in molecular chain length, the molecular packing of the compounds gradually changed from π–π stacked compact mode to X-crossing stacked loose mode, which leads to different stimuli-responsive phenomena of these compounds. The strategy provided herein facilitates the construction of multistimuli-responsive (thermochromism, mechanochromism, and vapochromism) OSFs with adjustable emission color. Harnessing the heat-responsive luminescence properties and great solubility of T12-Py, the optical information anticounterfeiting based on temperature was demonstrated by printing different concentrations of T12-Pysolution on filter papers. Much more, this research may provide broad implications for the design of organic smart materials based on intermolecular interactions.

Dendrimers, notable for their well-defined radial structures with numerous terminal functionalities, hold great promise for biomedical applications such as drug delivery, diagnostics, and therapeutics. However, their translation into clinical use has been greatly impeded by their challenging stepwise synthesis and difficult purification.

ABSTRACTBackgroundBaricitinib is approved for the treatment of rheumatoid arthritis (RA). The authors retrospectively investigated adverse events (AEs) by data-mining a self-reporting database to better understand toxicities, especially since it has been used during the coronavirus disease 2019 (COVID-19) pandemic.MethodsA reporting odds ratio (ROR) was used to detect the risk signals from the data in the US Food and Drug Administration (FDA) adverse event reporting system database (FAERS). The definition relied on system organ class (SOCs) and preferred terms (PTs) by the Medical Dictionary for Regulatory Activities (MedDRA).ResultsThe search retrieved 1,598 baricitinib-associated cases within the reporting period: 86 PTs with significant disproportionality were retained. Infections including ‘herpes zoster,’ ‘oral herpes,’ and ‘herpes virus infection’ were found at a similar rate to those reported in trials, and such events were rare. Reports emerged for several thrombotic adverse events, while these events were also rare. Unexpected safety signals as opportunistic infections were detected. Serious outcomes as death and life-threatening outcomes accounted for 9.76% of the reported cases.ConclusionsThe incidence of these AEs does not appear above the background expected. These data are consistent with routine clinical observations and suggest the importance of pharmacovigilance.

There is currently an outbreak of respiratory disease caused by a novel coronavirus. The virus has been named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the disease it causes has been named coronavirus disease 2019 (COVID-19). More than 16% of patients developed acute respiratory distress syndrome, and the fatality ratio was 1%–2%. No specific treatment has been reported. Herein, we examined the effects of favipiravir (FPV) versus lopinavir (LPV)/ritonavir (RTV) for the treatment of COVID-19. Patients with laboratory-confirmed COVID-19 who received oral FPV (Day 1: 1600 mg twice daily; Days 2–14: 600 mg twice daily) plus interferon (IFN)-α by aerosol inhalation (5 million international unit (IU) twice daily) were included in the FPV arm of this study, whereas patients who were treated with LPV/RTV (Days 1–14: 400 mg/100 mg twice daily) plus IFN-α by aerosol inhalation (5 million IU twice daily) were included in the control arm. Changes in chest computed tomography (CT), viral clearance, and drug safety were compared between the two groups. For the 35 patients enrolled in the FPV arm and the 45 patients in the control arm, all baseline characteristics were comparable between the two arms. A shorter viral clearance median time was found for the FPV arm versus the control arm (4 d (interquartile range (IQR): 2.5–9) versus 11 d (IQR: 8–13), P< 0.001). The FPV arm also showed significant improvement in chest CT compared with the control arm, with an improvement rate of 91.43% versus 62.22% (P = 0.004). After adjustment for potential confounders, the FPV arm also showed a significantly higher improvement rate in chest CT. Multivariable Cox regression showed that FPV was independently associated with faster viral clearance. In addition, fewer adverse events were found in the FPV arm than in the control arm. In this open-label before-after controlled study, FPV showed better therapeutic responses on COVID-19 in terms of disease progression and viral clearance. These preliminary clinical results provide useful information of treatments for SARS-CoV-2 infection.

A recent outbreak of pneumonia in Wuhan, China was found to be caused by a 2019 novel coronavirus (2019-nCoV or SARS-CoV-2 or HCoV-19). We previously reported the clinical features of 12 patients with 2019-nCoV infections in Shenzhen, China. To further understand the pathogenesis of COVID-19 and find better ways to monitor and treat the disease caused by 2019-nCoV, we measured the levels of 48 cytokines in the blood plasma of those 12 COVID-19 patients. Thirty-eight out of the 48 measured cytokines in the plasma of 2019-nCoV-infected patients were significantly elevated compared to healthy individuals. Seventeen cytokines were linked to 2019-nCoV loads. Fifteen cytokines, namely M-CSF, IL-10, IFN-α2, IL-17, IL-4, IP-10, IL-7, IL-1ra, G-CSF, IL-12, IFN-γ, IL-1α, IL-2, HGF and PDGF-BB, were strongly associated with the lung-injury Murray score and could be used to predict the disease severity of 2019-nCoV infections by calculating the area under the curve of the receiver-operating characteristics. Our results suggest that 2019-nCoV infections trigger extensive changes in a wide array of cytokines, some of which could be potential biomarkers of disease severity of 2019-nCoV infections. These findings will likely improve our understanding of the immunopathologic mechanisms of this emerging disease. Our results also suggest that modulators of cytokine responses may play a therapeutic role in combating the disease once the functions of these elevated cytokines have been characterized.

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan, Hubei province, and rapidly spread to many provinces in China as well as other countries. Here we report the epidemiological, clinical, laboratory, and radiological characteristics, as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen, China. All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS). The most common laboratory abnormalities were hypoalbuminemia, lymphopenia, decreased percentage of lymphocytes (LYM) and neutrophils (NEU), elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH), and decreased CD8 count. The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity. ALB, LYM, LYM (%), LDH, NEU (%), and CRP were highly correlated to the acute lung injury. Age, viral load, lung injury score, and blood biochemistry indexes, albumin (ALB), CRP, LDH, LYM (%), LYM, and NEU (%), may be predictors of disease severity. Moreover, the Angiotensin II level in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury. Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.

Chemokine‐like factor (CKLF)‐like, MAL and related proteins for vesicle trafficking and membrane link (MARVEL) transmembrane domain‐containing family proteins (CMTMs) have significant roles in the immune system, in male reproduction, as well as in tumorigenesis. Previous studies have shown that CMTM family member 7 (CMTM7) was broadly expressed in various normal tissues, but not in lung, gastric, esophageal, pancreas, and cervix cancers. To explore its relationship with liver cancer, we examined the expression of CMTM7 in liver cancers and its correlation with clinical and pathological conditions. We found that CMTM7 expression was markedly reduced in liver cancer tissues, and negatively correlated with TNM staging and tumor metastasis. In vitro studies showed that enforced expression of CMTM7 inhibited the cell growth and migration of liver cancer cells. Further analysis revealed that CMTM7 suppressed AKT signaling and induced cell cycle arrest at the G0/G1 phase in the liver cancer cells, likely as the consequent of decreased levels of cyclin D1, cyclin‐dependent kinase 4 (CDK4), and CDK6, and increased p27 expression. Thus, CMTM7 functions as a tumor suppressor in liver cancer through suppressing cell cycle progression.

Choline and its metabolites have diverse and important functions in many physiological processes, especially for anabolic metabolism in growth and reproduction. Besides endogenous biosynthesis and direct choline supplement, choline esters in the diet are another source of choline in the body. Phenolic choline esters are a group of unique dietary choline esters rich in the seeds of Brassicaceae plants, among which sinapine is a choline ester of sinapic acid abundant in rapeseed. In this study, 40 nursery pigs were fed with rapeseed-derived feed ingredients (RSF) or soybean meal for 3 weeks (20 pigs/diet). The metabolic fate of sinapine-derived choline in RSF was examined by comparing the distribution of choline and its metabolites in digesta, liver, and serum samples by liquid chromatography–mass spectrometry analysis. The results showed that choline was released from extensive hydrolysis of sinapine in the small intestine. However, sinapine-derived choline did not increase the levels of choline and its major metabolites, including betaine, phosphocholine, and glycerophosphocholine, in the liver and serum. Instead, RSF feeding increased trimethylamine (TMA), the microbial metabolite of choline, in the large intestine and further increased trimethylamine N-oxide (TMAO), the oxidation metabolite of TMA, in the liver and serum. Overall, these results suggested that sinapine-derived choline from rapeseed feeding had limited influences on the post-absorption choline pool as a result of its low bioavailability but may serve as a major source of TMAO through microbial metabolism in nursery pigs. Improving the bioavailability of sinapine-derived choline might have the potential to modify the nutritional values and functionalities of rapeseed meal in swine feeding.

The development of a sensitive and practical electrochemiluminescence (ECL) bioassay relies on the use of ECL signal tags whose signal intensity is high and stable. In this work, strong ECL emission was achieved from metal organic framework (MOF) accelerator enriched quantum dots (CdTe), which were applied as an efficient ECL signal tag for trace biomarker detection. It is particularly noteworthy that a novel mechanism to drastically enhance the ECL intensity of CdTe is established because isoreticular metal organic framework-3 (IRMOF-3) with 2-amino terephthalic acid (2-NH2-BDC) as the organic ligand not only allows for loading a large amount of CdTe via the encapsulating effect and internal/external decoration but also functions as a novel coreactant accelerator for promoting the conversion of coreactant S2O82–into the sulfate radical anion (SO4•–), further boosting the ECL emission of CdTe. On the basis of the simple sandwich immunoreaction approach, cardiac troponin-I antigen (cTnI), a kind of biomarker related with myocardial infarction, was chosen as a detection model using an IRMOF-3-enriched CdTe labeled antibody as the signal probe. This immunosensor demonstrated desirable assay performance for cTnI with a wide response range from 1.1 fg mL–1to 11 ng mL–1and a very low detection limit (0.46 fg mL–1). This suggested that the IRMOF-3-enriched CdTe nanocomposite strategy can integrate the coreactant accelerator and luminophore to significantly enhance the ECL intensity and stability, providing a direction for promising ECL tag preparation with broad applications.

Oxetane has been extensively studied for its applications in medicinal chemistry and as a reactive intermediate in synthesis. Experiments report a Cu-catalyzed [2 + 2] photocycloaddition of acetone and norbornene to oxetane, which is proposed to deviate from the conventional Paternò-Büchi reaction. However, its mechanism at the atomic level is not clear. In this study, we used a combination of multistate complete active space second-order perturbation theory (MS-CASPT2) and density functional theory to systematically investigate the reaction mechanism and elucidate the factors contributing to the diastereomeric selectivity. Initially, the formation of the TpCu(Norb) complex is achieved by strong interaction between tris(pyrazolyl)borate Cu(I) (TpCu) and norbornene in the ground state (S0). Upon photoexcitation, TpCu(Norb) eventually decays to the T1state, in which TpCu(Norb) attacks acetone to initiate subsequent reactions and produces final endo- or exo-oxetane products. All these reactions initially involve the C–C bond formation in the T1state thereto leading to a ring-opening intermediate. This intermediate then undergoes a nonradiative transition to the S0state, producing a five-membered ring intermediate, from which the C–O bond is formed, leading to the experimentally dominant exo-product. In contrast, the endo-oxetane formation requires a rearrangement process after the C–C bond is formed because of the large steric effects. As a consequence, the different reaction pathways generating exo- and endo-products exhibit large differences in the free-energy barriers, which results in a diastereomeric selectivity observed experimentally. Additionally, the nonradiative transition is found to play an important role in facilitating these reaction steps. The present computational study provides valuable mechanistic insights into Cu-catalyzed photocycloaddition reactions.

Small interfering RNA (siRNA) is emerging as a novel therapeutic for treating various diseases, provided a safe and efficient delivery is available. In particular, specific delivery to target cells is critical for achieving high therapeutic efficacy while reducing toxicity. Amphiphilic dendrimers are emerging as novel promising carriers for siRNA delivery by virtue of the combined multivalent cooperativity of dendrimers with the self-assembling property of lipid vectors. Here, we report a ballistic approach for targeted siRNA delivery to cancer cells using an amphiphilic dendrimer equipped with a dual targeting peptide bearing an RGDK warhead. According to the molecular design, the amphiphilic dendrimer was expected to deliver siRNA effectively, while the aim of the targeting peptide was to home in on tumors via interaction of its warhead with integrin and the neuropilin-1 receptor on cancer cells. Coating the positively charged siRNA/dendrimer delivery complex with the negatively charged segment of the targeting peptide via electrostatic interactions led to small and stable nanoparticles which were able to protect siRNA from degradation while maintaining the accessibility of RGDK for targeting cancer cells and preserving the ability of the siRNA to escape from endosomes. The targeted system had enhanced siRNA delivery, stronger gene silencing, and more potent anticancer activity compared to nontargeted or covalent dendrimer-based systems. In addition, neither acute toxicity nor induced inflammation was observed. Consequently, this delivery system constitutes a promising nonviral vector for targeted delivery and can be further developed to provide RNAi-based personalized medicine against cancer. Our study also gives new perspectives on the use of nanotechnology based on self-assembling dendrimers in various biomedical applications.

Brain cancer is one of the most lethal and difficult-to-treat cancers because of its physical location and biological barriers. The mainstay of brain cancer treatment is surgical resection, which demands precise imaging for tumor localization and delineation. Thanks to advances in bioimaging, brain cancer can be detected earlier and resected more reliably. Magnetic resonance imaging (MRI) is the most common and preferred method to delineate brain cancer, and a contrast agent is often required to enhance imaging contrast. Dendrimers, a special family of synthetic macromolecules, constitute a particularly appealing platform for constructing MRI contrast agents by virtue of their well-defined three-dimensional structure, tunable nanosize and abundant surface terminals, which allow the accommodation of high payloads and numerous functionalities. Tuning the dendrimer size, branching and surface composition in conjunction with conjugation of MRI functionalities and targeting moieties can alter the relaxivity for MRI, overcome the blood-brain barrier and enhance tumor-specific targeting, hence improving the imaging quality and safety profile for precise and accurate imaging of brain tumors. This short review highlights the recent progress, opportunities and challenges in developing dendrimer-based MRI contrast agents for brain tumor imaging. 脑癌由于其特殊的生理位置和血脑屏障, 是一种难以治疗的致命肿瘤. 手术切除是目前脑癌的主要治疗手段, 然而成功的手术需要 精确的肿瘤定位和肿瘤成像以确保完全切除癌细胞并避免伤害正常脑组织. 磁共振成像是诊断脑癌最常见的成像方法, 但通常需要造影 剂来增强成像对比度和精准度. 树型分子因其独特的精准三维结构, 可调控的纳米尺寸和众多的表面官能团, 可作为构建磁共振成像造影 剂的优选材料. 藉由调整树型分子的尺寸、使用不同的分支结构和表面官能团修饰(包括磁共振成像功能团和脑肿瘤靶向基团), 可以改 善造影剂的弛豫性, 克服血脑屏障并增强肿瘤靶向能力, 从而改善成像质量以获得精准的脑瘤成像, 并提高造影剂的安全性. 本文简要总 结了基于树型分子的磁共振成像造影剂在脑癌成像应用中的挑战、最新进展、机遇和未来发展趋势.

Tooth development is a complex process that involves precise and time-dependent orchestration of multiple genetic, molecular, and cellular interactions. Ameloblastin (AMBN, also named “amelin” or “sheathlin”) is the second most abundant enamel matrix protein known to have a key role in amelogenesis. Amelogenesis imperfecta (AI [MIM: 104500]) refers to a genetically and phenotypically heterogeneous group of conditions characterized by inherited developmental enamel defects. The hereditary dentin disorders comprise a variety of autosomal-dominant genetic symptoms characterized by abnormal dentin structure affecting either the primary or both the primary and secondary teeth. The vital role of Ambnin amelogenesis has been confirmed experimentally using mouse models. Only two cases have been reported of mutations of AMBNassociated with non-syndromic human AI. However, no AMBNmissense mutations have been reported to be associated with both human AI and dentin disorders. We recruited one kindred with autosomal-dominant amelogenesis imperfecta (ADAI) and dentinogenesis imperfecta/dysplasia characterized by generalized severe enamel and dentin defects. Whole exome sequencing of the proband identified a novel heterozygous C-T point mutation at nucleotide position 1069 of the AMBNgene, causing a Pro to Ser mutation at the conserved amino acid position 357 of the protein. Exfoliated third molar teeth from the affected family members were found to have enamel and dentin of lower mineral density than control teeth, with thinner and easily fractured enamel, short and thick roots, and pulp obliteration. This study demonstrates, for the first time, that an AMBNmissense mutation causes non-syndromic human AI and dentin disorders. A mutation on a gene involved in healthy tooth development may cause both enamel and dentin disorders. The ameloblastin enamel protein, and its associated gene, AMBN, play vital roles in enamel formation and tooth remodelling. Mutations on AMBNcan cause amelogenesis imperfecta (AI), a genetic and hereditory condition resulting in enamel defects and severe tooth decay. Now, Fu Xiong and Bu-Ling Wu at Southern Medical University in Guangzhou, China, and co-workers have identified an AMBNmutation found in both enamel and dentin defect disorders. The researchers analyzed extracted teeth from a Chinese patient with both AI and a severe dentin disorder, along with teeth from affected and non-affected members of the same family, and compared the results with a control group. They identified a rare mutation on AMBNcommon to all affected individuals.

This paper aims to comprehensively understand a 3D model for simulating dam-break floods through three test cases. The advantages and characteristics of this model are evaluated from different perspectives. Firstly, vertical inertial is considered in the 3D model. In the existing 1D and 2D flooding models, vertical inertia is usually ignored, resulting in unreliable results in high vertical inertia situations. A circular dam break case was designed and widely used for testing 2D models. Here it has been adopted to test the 3D model. Evident difference has been observed when compared with 2D modelling results. In order to reduce the vertical inertial in this case, we scaled the vertical size by 1:100, while kept the original horizontal size, then amplified the results according to the Froude number scaling rule. The results of the scaled model is very close to 2D modelling results. Therefore, the difference between the 3D and 2D modelling results are mainly caused by the vertical inertia. Thus it can be seen that 3D modelling techniques are needed when vertical inertia is not negligible. Secondly, the use of unstructured mesh makes this model more powerful in operating with complex topography, which is very important in real-world application. Five similar cases with different topography demonstrated that the complexity of topography affects the numerical solution process directly. However, this 3D model has powerful ability in utilizing very complex terrain. Thirdly, sensitivity of the model to the thickness of the artificial thin layer in dry areas ( d 0 ) and mesh resolution ( Δx ) have been analysed with a realistic dike-break flooding case. Smaller d 0 produces more realistic results but costs more computational time. The model is more sensitive to mesh resolution when the terrain is more complex. Therefore, a multi-scale mesh with high-resolution in areas with complex terrain and low-resolution in flat regions is a good choice for this model. Also, trade-offs between modelling precision and efficiency should be considered when choosing a proper value of d 0 and mesh resolution. [ABSTRACT FROM AUTHOR]

Metastasis is the cause of most (>90%) cancer deaths and currently lacks effective treatments. Approaches to understanding the biological process, unraveling the most effective molecular target(s), and implementing nanotechnology to increase the therapeutic index are expected to facilitate cancer therapy against metastasis. Here, we demonstrate the potential advantages of bringing these three approaches together through the rational design of a small interfering RNA (siRNA) that targets p70S6Kin cancer stem cells (CSCs) in combination with dendrimer nanotechnology-based siRNA delivery. Our results demonstrated that the generation 6 (G6) poly(amidoamine) dendrimer can be used as a nanovector to effectively deliver p70S6KsiRNA by forming uniform dendriplex nanoparticles that protect the siRNA from degradation. These nanoparticles were able to significantly knock down p70S6Kin ovarian CSCs, leading to a marked reduction in CSC proliferation and expansion without obvious toxicity toward normal ovarian surface epithelial cells. Furthermore, treatment with the p70S6KsiRNA/G6dendriplexes substantially decreased mesothelial interaction, migration and invasion of CSCs in vitro, as well as tumor growth and metastasis in vivo. Collectively, these results suggest that p70S6Kconstitutes a promising therapeutic target, and the use of siRNA in combination with nanotechnology-based delivery may constitute a new approach for molecularly targeted cancer therapy to treat metastasis.

Airway remodeling is a key feature of asthma, characterized by increased proliferation of airway smooth muscle cells (ASMCs). S100A8 is a calcium-binding protein with a potential to regulate cell proliferation. Here, the effect of exogenous S100A8 protein on the proliferation of ASMCs induced by platelet-derived growth factor (PDGF) and the underlying molecular mechanism was investigated. Rat ASMCs were cultured with or without a neutralizing antibody to the receptor for advanced glycation end-products (RAGE), a potential receptor for S100A8 protein. Purified recombinant rat S100A8 protein was then added into the cultured cells, and the proliferation of ASMCs induced by PDGF was detected by colorimetric-based WST-8 assay and ampedance-based xCELLigence proliferation assay. The expression levels of RAGE in ASMCs were analyzed using western blotting assay. Results showed that exogenous S100A8 inhibited the PDGF-induced proliferation of rat ASMCs in a dose-dependent manner with the maximal effect at 1 μg/ml in vitro. Furthermore, when ASMCs was pre-treated with anti-RAGE neutralizing antibody, the inhibitory effect of S100A8 on PDGF-induced proliferation was significantly suppressed. In addition, neither the treatment with S100A8 or PDGF alone nor the pre-treatment with rS100A8 followed by PDGF stimulation affected the expression levels of RAGE. Our study demonstrated that S100A8 inhibits PDGF-induced ASMCs proliferation in a manner dependent on membrane receptor RAGE.

In this paper, the passivation quality of crystalline silicon (c-Si) wafers, when passivated by atomic layer deposited aluminum oxide (ALD AlOx), is investigated. Specifically, we investigated the effect of surface modification of the c-Si interface prior to the ALD AlOx deposition (via -H and -OH termination of the c-Si wafer) over a large range of AlOx thicknesses (0.4-80 nm). Fourier transform infrared (FTIR) studies confirmed the presence of -H and -OH termination on c-Si surface. In general, surface passivation on -OH terminated wafers was found to be better than their -H terminated counterparts, which is consistent with correspondingly measured density of interface defects, and density of fixed interface charge. In all cases, the formation of an additional interfacial SiOx layer between the c-Si/AlOx interface was revealed. The corresponding Si-oxide peaks, as measured by X-ray photoelectron spectroscopy (XPS), were found to be stronger for -OH terminated c-Si surfaces. The thickness of the interfacial SiOx layer was measured by high-resolution transmission electron microscopy. Thus, despite the superior surface passivation of -OH terminated c-Si wafers, for the ALD AlOx tunnel layers of 0.4-2 nm (i.e., on the order necessary to form passivated contacts for solar cells), there is a trade-off between the better passivation achieved by the thicker SiOx interfacial layers (-OH termination), and the correspondingly higher tunneling resistance due to the overall larger effective tunnel layer thickness.