Purinergic Receptor Antagonists Inhibit Hemolysis Induced by Clostridium perfringens Alpha Toxin.

Clostridium perfringens alpha toxin (CPA), which causes yellow lamb disease in sheep and gas gangrene and food poisoning in humans, is produced by all types of C. perfringens and is the major virulence determinant of C. perfringens type A. CPA induces hemolysis in many species, including humans, murines, sheep and rabbits, through its enzymatic activity, which dissolves the cell membrane. Recent studies have shown that some pore-forming toxins cause hemolysis, which is achieved by the activation of purinergic receptors (P2). However, the relationship between P2 receptors and non-pore-forming toxin hemolysis has not been investigated. In the present study, we examined the function of P2 receptors in CPA toxin hemolysis and found that CPA-induced hemolysis was dependent on P2 receptor activation, and this was also true for Staphylococcus aureus ß-Hemolysin, another non-pore-forming toxin. Furthermore, we use selective P2 receptor antagonists to demonstrate that P2X1 and P2X7 play important roles in the hemolysis of human and murine erythrocytes. In addition, we found that redox metabolism was mainly involved in CPA-induced hemolysis using metabolomic analysis. We further demonstrate that CPA activates P2 receptors and then activates NADPH oxidase through the PI3K/Akt and MEK1/ERK1 pathways, followed by the production of active oxygen to induce hemolysis. These findings contribute to our understanding of the pathological effects of CPA, clarify the relationship between P2 activation and non-pore-forming toxin-induced hemolysis, and provide new insights into CPA-induced hemolysis.

Mapping Knowledge Landscapes and Emerging Trends of Sarcopenic Obesity in Older Adults: A Bibliometric Analysis From 2004 to 2023.

Background The prevalence of obesity in combination with sarcopenia, the age-related loss of muscle mass and strength or physical function, is on the rise among adults aged 65 years and older. A significant portion of this demographic now falls under the classification of sarcopenic obesity, a high-risk geriatric syndrome predominantly seen in an aging population vulnerable to compounded complications from both sarcopenia and obesity. It is essential to promptly evaluate the impact of academic research in this field, taking into account factors such as geographical regions, authors, journals, and institutions. Furthermore, exploring current topics and identifying potential areas that could inspire future researchers to conduct additional studies is crucial for advancing overall health in this population. Methodology A search was conducted in the Web of Science Core Collection database to identify English language articles and reviews focusing on sarcopenic obesity in older adults, published between January 1, 2004, and December 31, 2023. Bibliometric analysis was performed using VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2). Results A total of 985 original English-language articles were collected, consisting of 783 articles and 202 reviews. The volume of research publications in this field has shown significant growth since 2012. The United States leads in contributions, with 239 articles (24.3% of the total) and the highest number of citations at 18,403, along with the highest total link strength. The University of Melbourne in Australia stands out with 25 published articles (2.5% of the total). University of Verona in Italy has the most citations at 9,405, and Monash University in Australia has the highest total link strength at 53. Among prolific authors, John A. Batsis from Duke University is the most productive with 24 articles (2.4% of the total). The journal "Nutrients" has the most articles on sarcopenic obesity in older adults, publishing 54 articles (5.5% of the total). Key topics in this area include sarcopenia, obesity, sarcopenic obesity, and elderly. Recent interventions focus on "nutrition" and "exercise" for sarcopenic obesity in older adults. Conclusions Research on sarcopenic obesity in older adults has seen significant growth on a global scale from 2004 to 2023, indicating a promising area for further study with potential benefits from current advancements. Although academic inquiries have shed light on various aspects of sarcopenic obesity in older adults, there remains a noticeable dearth of clinical research and evidence-based medicine on the effective management of this condition in elderly individuals. Future studies could focus on developing tailored interventions for older adults with sarcopenic obesity.

Different prognosis in cutaneous early-onset and late-onset Merkel cell carcinoma: a population-based retrospective study.

BACKGROUND: Merkel cell carcinoma (MCC) is a rare and highly aggressive form of skin cancer. However, there is limited research on the clinicopathological features of early-onset MCC (EOMCC) and the differences between EOMCC and late-onset MCC (LOMCC). Our objective was to evaluate the clinicopathological features and cancer-specific survival (CSS) of EOMCC. METHODS: Our cohort study analyzed data from the Surveillance, Epidemiology, and End Results (SEER) database from January 1, 2018, to December 31, 2020. Data from 1941 patients who were diagnosed with primary cutaneous MCC were included. We then divided the patients with MCC into two groups: those with EOMCC (526 patients) and those with LOMCC (1415 patients). CSS is used as the primary outcome. RESULTS: The EOMCC group exhibited trends toward advanced tumor progression, an expanded surgical scope, increased lymph node retrieval, intensified radiotherapy, greater utilization of systemic therapy, and a better prognosis. Multivariate analysis revealed that LOMCC (HR 3.305 [2.002-5.456], P < 0.001), advanced T stage (HR 1.430 [1.139-1.797], P = 0.002), advanced N stage (HR 1.522 [1.221-1.897], P < 0.001), M1 stage (HR 2.587 [1.480-4.521], P < 0.001), and radiation (HR 0.586 [0.410-0.837], P = 0.003) were significantly associated with CSS. Among these factors, EOMCC/LOMCC was most strongly associated with CSS, indicating that LOMCC is an independent risk factor for CSS. Interestingly, we found that regional EOMCC and localized or in situ LOMCC had almost completely overlapping survival curves (Plog-rank = 0.620). Additionally, we observed that the TNM staging + age model was a more accurate predictor of CSS among MCC patients than using TNM staging alone. CONCLUSIONS: We found that EOMCC has distinct clinicopathological features compared to LOMCC. EOMCC is associated with better CSS. The combination of TNM staging and age was more accurate for predicting patient outcomes than TNM staging alone.

Integrated and DC-powered superconducting microcomb.

Frequency combs, specialized laser sources emitting multiple equidistant frequency lines, have revolutionized science and technology with unprecedented precision and versatility. Recently, integrated frequency combs are emerging as scalable solutions for on-chip photonics. Here, we demonstrate a fully integrated superconducting microcomb that is easy to manufacture, simple to operate, and consumes ultra-low power. Our turnkey apparatus comprises a basic nonlinear superconducting device, a Josephson junction, directly coupled to a superconducting microstrip resonator. We showcase coherent comb generation through self-started mode-locking. Therefore, comb emission is initiated solely by activating a DC bias source, with power consumption as low as tens of picowatts. The resulting comb spectrum resides in the microwave domain and spans multiple octaves. The linewidths of all comb lines can be narrowed down to 1 Hz through a unique coherent injection-locking technique. Our work represents a critical step towards fully integrated microwave photonics and offers the potential for integrated quantum processors.

[Cell membrane-coated nanoparticles in disease therapy].

Nanotechnology has attracted increasing attention in the field of medical applications due to its significant potential for development. However, one major challenge that has emerged with nanoparticles is their tendency to activate the host immune clearance system, which hampers the achievement of desired therapeutic outcomes and may lead to harmful side effects. In recent years, membrane-coated nanoparticles have emerged as a promising solution, demonstrating their effectiveness in evading immune system clearance. These innovative nanoparticles inherit essential biological attributes from natural cell membranes, such as anchoring proteins and antigens. Consequently, membrane-coated nanoparticles exhibit unique capabilities such as immune evasion, prolonged circulation, targeted drug release, and immune modulation, substantially enhancing their versatility and prospects within the realm of biomedical applications. This review provides a comprehensive overview of the current applications of cell membrane-coated nanoparticles in disease therapy, highlighting their immense potential in this rapidly evolving platform. Additionally, the review outlines the promising prospects of this technology in disease therapy.

Biological scaffold as potential platforms for stem cells: Current development and applications in wound healing.

Wound repair is a complex challenge for both clinical practitioners and researchers. Conventional approaches for wound repair have several limitations. Stem cell-based therapy has emerged as a novel strategy to address this issue, exhibiting significant potential for enhancing wound healing rates, improving wound quality, and promoting skin regeneration. However, the use of stem cells in skin regeneration presents several challenges. Recently, stem cells and biomaterials have been identified as crucial components of the wound-healing process. Combination therapy involving the development of biocompatible scaffolds, accompanying cells, multiple biological factors, and structures resembling the natural extracellular matrix (ECM) has gained considerable attention. Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells, providing them with an environment conducive to growth, similar to that of the ECM. These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing. This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing, emphasizing their capacity to facilitate stem cell adhesion, proliferation, differentiation, and paracrine functions. Additionally, we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Mapping Knowledge Landscapes and Emerging Trends of the Links Between Frailty and Heart Failure: A Bibliometric Analysis From 2000 to 2023.

Background Frailty, within the context of heart failure (HF), is strongly linked to poor patient outcomes. Investigating the vulnerable condition of individuals with HF is crucial, not only for medical reasons but also as a significant public health challenge, especially among the elderly population where both HF and frailty are common. Therefore, it is essential to prioritize HF patients with frailty over those without such symptoms. To begin, promptly assessing the impact of academic research in this area is crucial, considering factors such as geographical regions, authors, journals, and institutions. Additionally, it is important to explore current topics and identify potential areas that could inspire future researchers to conduct further studies to advance public health. Methodology We conducted a search in the Web of Science Core Collection database to identify articles and reviews in the English language focusing on frailty and HF which were published from January 1, 2000, to December 31, 2023. To perform bibliometric analysis, VOSviewer (v.1.6.18) and CiteSpace (v.6.1.R2) were utilized. Results A total of 1,381 original English-language articles were gathered, comprising 1,162 articles and 219 reviews. The quantity of research publications in this area has experienced significant growth since 2013. Among all countries, the United States has contributed the largest number of publications, accounting for 409 articles (29.62% of the total). Additionally, the United States has received the highest number of citations, being cited a total of 13,329 times, as well as boasting the greatest total link strength. Duke University stands out as the institution with the highest number of research papers, having published 40 articles (2.90% of the total). It has also received the most citations, with a total of 2,455 times, and possesses the highest total link strength, which amounts to 212. Within the realm of prolific authors, Kentaro Kamiya from Kitasato University emerges as the most productive, having authored 28 articles (2.03% of the total). When considering scholarly journals, "Esc Heart Failure" contains the highest number of articles pertaining to frailty and HF, publishing a noteworthy 36 articles (2.61% of the total). Noteworthy keywords within this field encompass frailty, heart failure, elderly, mortality, and cardiovascular disease. Over the past five years, the most popular keywords have centered around "frailty syndrome," "sarcopenia," and "therapeutic interventions." Conclusions Research on frailty and HF at a global scale has experienced substantial growth between 2000 and 2023, demonstrating a prospective field for further exploration with potential advantages from ongoing progress. Prospective studies could prioritize the enhancement of cardiac rehabilitation for patients coping with HF and frailty while ensuring the preservation of their overall quality of life.

Albumin-bilirubin grade as a predictor of survival in hepatocellular carcinoma patients with thrombocytopenia.

BACKGROUND: The models for assessing liver function, mainly the Child-Pugh (CP), albuminbilirubin (ALBI), and platelet-ALBI (PALBI) classifications, have been validated for use in estimating the prognosis of hepatocellular carcinoma (HCC) patients. However, thrombocytopenia is a common finding and may influence the prognostic value of the three models in HCC. AIM: To investigate and compare the prognostic performance of the above three models in thrombocytopenic HCC patients. METHODS: A total of 135 patients with thrombocytopenic HCC who underwent radical surgery were retrospectively analyzed. Preoperative scores on the CP, ALBI and PALBI classifications were estimated accordingly. Kaplan-Meier curves with log-rank tests and Cox regression models were used to explore the significant factors associated with overall survival (OS) and recurrence-free survival (RFS). RESULTS: The preoperative platelet counts were significantly different among the CP, ALBI and PALBI groups. After a median follow-up of 28 mo, 39.3% (53/135) of the patients experienced postoperative recurrence, and 36.3% (49/135) died. Univariate analysis suggested that α-fetoprotein levels, tumor size, vascular invasion, and ALBI grade were significant predictors of OS and RFS. According to the multivariate Cox regression model, ALBI was identified as an independent prognostic factor. However, CP and PALBI grades were not statistically significant prognostic indicators. CONCLUSION: The ALBI grade, rather than CP or PALBI grade, is a significant prognostic indicator for thrombocytopenic HCC patients.

A Case of Pulmonary Actinomycosis With Concurrent Gastric Adenocarcinoma in an Older Adult.

Actinomycosis is a chronic granulomatous disease that can affect various parts of the body, including the head and neck, lungs, abdominal and pelvic cavities, and wounds. It is caused by different actinomycetes like Actinomyces sherdii, Actinomyces glasii, Actinomyces cariosa, Actinomyces zurichensis, and Actinomyces europaea. Reported infections caused by actinomycetes include pulmonary actinomycosis, pelvic and abdominal infections, bone or artificial joint infections, endocarditis, complicated urinary tract infections, and soft tissue abscesses. The combination of pulmonary actinomycosis with gastric cancer is exceptionally rare in clinical practice, and the presence of actinomycetal infection alongside tumors in elderly patients poses significant challenges in treatment. This article presents the diagnosis and treatment process of an elderly patient with pulmonary actinomycosis and gastric adenocarcinoma.

Effectiveness of personalized meal recommendation in improving dietary behaviors of Chinese community-dwelling elders: study protocol for a cluster randomized controlled trial.

BACKGROUND: Inappropriate eating behaviors, particularly a lack of food diversity and poor diet quality, have a significant impact on the prognosis of certain chronic conditions and exacerbate these conditions in the community-dwelling elderly population. Current dietary interventions for the elderly have not adequately considered the nutritional needs associated with multiple chronic conditions and personal dietary preferences of elderly individuals. A personalized recommendation system has been recognized as a promising approach to address this gap. However, its effectiveness as a component of an elderly-targeted dietary intervention in real-world settings remains unknown. Additionally, it is unclear whether this intervention approach will be user-friendly for the elderly. Therefore, this study aims to examine the effectiveness of a personalized meal recommendation system designed to improve dietary behavior in community-dwelling elders. The implementation process in terms of System usability and satisfaction will also be assessed. METHODS: The trial has been designed as a 6-month, non-blinded, parallel two-arm trial. One hundred fifty community-dwelling elders who meet the eligibility criteria will be enrolled. Subjects will be allocated to either the intervention group, receiving personalized meal recommendations and access to corresponding food provided as one component of the intervention, as well as health education on elder nutrition topics, or the control group, which will receive nutritional health education lectures. Outcomes will be measured at three time points: baseline at 0 months, 3 months, and 6 months. The primary outcomes will include dietary diversity (DDS) and diet quality (CDGI-E) of enrolled community-dwelling elders, representing their dietary behavior improvement, along with dietary behavior adherence to recommended meals. Secondary outcomes will measure the perceived acceptability and usability of the personalized meal recommendation system for the intervention group. Exploratory outcomes will include changes in the nutritional status and anthropometric measurements of the community-dwelling elders. DISCUSSION: This study aims to examine the effectiveness, acceptability, and usability of a personalized meal recommendation system as a data-driven dietary intervention to benefit community-dwelling elders. The successful implementation will inform the future development and integration of digital health strategies in daily nutrition support for the elderly. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2300074912. Registered on August 20, 2023, https://www.chictr.org.cn/showproj.html?proj=127583.

Toroidic phase transitions in a direct-kagome artificial spin ice.

Ferrotoroidicity-the fourth form of primary ferroic order-breaks both space and time-inversion symmetry. So far, direct observation of ferrotoroidicity in natural materials remains elusive, which impedes the exploration of ferrotoroidic phase transitions. Here we overcome the limitations of natural materials using an artificial nanomagnet system that can be characterized at the constituent level and at different effective temperatures. We design a nanomagnet array as to realize a direct-kagome spin ice. This artificial spin ice exhibits robust toroidal moments and a quasi-degenerate ground state with two distinct low-temperature toroidal phases: ferrotoroidicity and paratoroidicity. Using magnetic force microscopy and Monte Carlo simulation, we demonstrate a phase transition between ferrotoroidicity and paratoroidicity, along with a cross-over to a non-toroidal paramagnetic phase. Our quasi-degenerate artificial spin ice in a direct-kagome structure provides a model system for the investigation of magnetic states and phase transitions that are inaccessible in natural materials.

Obesity fosters severe disease outcomes in a mouse model of coronavirus infection associated with transcriptomic abnormalities.

Obesity has been identified as an independent risk factor for severe outcomes in humans with coronavirus disease 2019 (COVID-19) and other infectious diseases. Here, we established a mouse model of COVID-19 using the murine betacoronavirus, mouse hepatitis virus 1 (MHV-1). C57BL/6 and C3H/HeJ mice exposed to MHV-1 developed mild and severe disease, respectively. Obese C57BL/6 mice developed clinical manifestations similar to those of lean controls. In contrast, all obese C3H/HeJ mice succumbed by 8 days postinfection, compared to a 50% mortality rate in lean controls. Notably, both lean and obese C3H/HeJ mice exposed to MHV-1 developed lung lesions consistent with severe human COVID-19, with marked evidence of diffuse alveolar damage (DAD). To identify early predictive biomarkers of worsened disease outcomes in obese C3H/HeJ mice, we sequenced RNA from whole blood 2 days postinfection and assessed changes in gene and pathway expression. Many pathways uniquely altered in obese C3H/HeJ mice postinfection aligned with those found in humans with severe COVID-19. Furthermore, we observed altered gene expression related to the unfolded protein response and lipid metabolism in infected obese mice compared to their lean counterparts, suggesting a role in the severity of disease outcomes. This study presents a novel model for studying COVID-19 and elucidating the mechanisms underlying severe disease outcomes in obese and other hosts.

Unconventional Superconducting Diode Effects via Antisymmetry and Antisymmetry Breaking.

Symmetry breaking plays a pivotal role in unlocking intriguing properties and functionalities in material systems. For example, the breaking of spatial and temporal symmetries leads to a fascinating phenomenon: the superconducting diode effect. However, generating and precisely controlling the superconducting diode effect pose significant challenges. Here, we take a novel route with the deliberate manipulation of magnetic charge potentials to realize unconventional superconducting flux-quantum diode effects. We achieve this through suitably tailored nanoengineered arrays of nanobar magnets on top of a superconducting thin film. We demonstrate the vital roles of inversion antisymmetry and its breaking in evoking unconventional superconducting effects, namely a magnetically symmetric diode effect and an odd-parity magnetotransport effect. These effects are nonvolatilely controllable through in situ magnetization switching of the nanobar magnets. Our findings promote the use of antisymmetry (breaking) for initiating unconventional superconducting properties, paving the way for exciting prospects and innovative functionalities in superconducting electronics.

Radiotherapy and Anrotinib in Malignant Glomus Tumor of the Bladder: A Case Report and Literature Review.

Background: Malignant glomus tumors (MGTs) are rare malignancies, which grow rapidly and are aggressive. Surgical resection has been regarded as the standard management, but treatment options for those unresectable tumors are limited, resulting in a high recurrence rate and poor prognosis. Case Description: An 85-year-old man presented with gross hematuria and was diagnosed with MGTs of bladder. The patient achieved long-term local control after multimodal therapy comprising radiotherapy, iodine-125 seeds brachytherapy, transcatheter arterial chemoembolization, and antiangiogenic targeted therapy. Conclusion: MGTs occurring in the bladder are clinically rare and refractory. The case presented here highlights the importance of multidisciplinary diagnosis and treatment, providing evidence that radiotherapy and antiangiogenic therapy may play an important role in unresectable bladder MGT.

Linear and phase controllable terahertz frequency conversion via ultrafast breaking the bond of a meta-molecule.

The metasurface platform with time-varying characteristics has emerged as a promising avenue for exploring exotic physics associated with Floquet materials and for designing photonic devices like linear frequency converters. However, the limited availability of materials with ultrafast responses hinders their applications in the terahertz range. Here we present a time-varying metasurface comprising an array of superconductor-metal hybrid meta-molecules. Each meta-molecule consists of two meta-atoms that are "bonded" together by double superconducting microbridges. Through experimental investigations, we demonstrate high-efficiency linear terahertz frequency conversion by rapidly breaking the bond using a coherent ultrashort terahertz pump pulse. The frequency and relative phase of the converted wave exhibit strong dependence on the pump-probe delay, indicating phase controllable wave conversion. The dynamics of the meta-molecules during the frequency conversion process are comprehensively understood using a time-varying coupled mode model. This research not only opens up new possibilities for developing innovative terahertz sources but also provides opportunities for exploring topological dynamics and Floquet physics within metasurfaces.

Skeletal muscle extramedullary plasmacytoma transformed into plasmablastic plasmacytoma: a case report.

BACKGROUND: Extramedullary plasmacytoma (EMP) is a rare plasma cell malignancy, especially when the tumor originates in skeletal muscle. Plasmablastic plasmacytoma is an anaplastic round cell tumor with highly malignancy and poor prognosis. To date, there have been no reports on the transformation of skeletal muscle EMP into plasmablastic plasmacytoma. Therefore, the diagnosis, treatment, and prognosis of cases of this pathologic transformation are unclear. CASE PRESENTATION: This article reports a case of an elderly male patient who presented with a painless mass in the right calf and was diagnosed with EMP by puncture pathology. Complete remission was obtained after sequential chemoradiotherapy. 6 months later, another puncture was performed due to plasmablastic plasmacytoma multiple distant metastases, and the pathology showed that EMP was transformed to plasmablastic plasmacytoma. Despite aggressive antitumor therapy, the disease continued to deteriorate, and the patient ultimately died of respiratory failure. CONCLUSION: The transformation of EMP into plasmablastic plasmacytoma is very rare, and its diagnosis and treatment require the participation of both experienced pathologists and clinicians. We report this case in order to raise clinicians' awareness of the diagnosis and treatment of EMP and its transformation to plasmablastic plasmacytoma, and to avoid misdiagnosis and underdiagnosis.

Disparate processing of numerosity and associated continuous magnitudes in rats.

The studies of number sense in different species are severely hampered by the inevitable entanglement of non-numerical attributes inherent in nonsymbolic stimuli representing numerosity, resulting in contrasting theories of numerosity processing. Here, we developed an algorithm and associated analytical methods to generate stimuli that not only minimized the impact of non-numerical magnitudes in numerosity perception but also allowed their quantification. We trained number-naïve rats with these stimuli as sound pulses representing two or three numbers and demonstrated that their numerical discrimination ability mainly relied on numerosity. Also, studying the learning process revealed that rats used numerosity before using magnitudes for choices. This numerical processing could be impaired specifically by silencing the posterior parietal cortex. Furthermore, modeling this capacity by neural networks shed light on the separation of numerosity and magnitudes extraction. Our study helps dissect the relationship between magnitude and numerosity processing, and the above different findings together affirm the independent existence of innate number and magnitudes sense in rats.

Magnesium Depletion Score and Metabolic Syndrome in US Adults: Analysis of NHANES 2003-2018.

BACKGROUND: The association between magnesium status and metabolic syndrome remains unclear. This study aimed to examine the relationship between the kidney reabsorption-related magnesium depletion score (MDS) and metabolic syndrome among US adults. METHODS: We analyzed data from 15,565 adults participating in the National Health and Nutrition Examination Survey (NHANES) 2003-2018. Metabolic syndrome was defined according to the National Cholesterol Education Program's Adult Treatment Panel III report. The MDS is a scoring system developed to predict the status of magnesium deficiency that fully considers the pathophysiological factors influencing the kidneys' reabsorption capability. Weighted univariate and multivariate logistic regression were used to assess the association between MDS and metabolic syndrome. Restricted cubic spline analysis was conducted to characterize dose-response relationships. Stratified analyses by sociodemographic and lifestyle factors were also performed. RESULTS: In both univariate and multivariate analyses, higher MDS was significantly associated with increased odds of metabolic syndrome. Each unit increase in MDS was associated with approximately a 30% higher risk for metabolic syndrome, even after adjusting for confounding factors (OR 1.31; 95% CI 1.17-1.45). Restricted cubic spline graphs depicted a linear dose-response relationship across the MDS range. This positive correlation remained consistent across various population subgroups and exhibited no significant interaction by age, gender, race, adiposity, smoking status, or alcohol consumption. CONCLUSIONS: Higher urinary magnesium loss as quantified by MDS may be an independent linear risk factor for metabolic syndrome in US adults, irrespective of sociodemographic and behavioral factors. Optimizing magnesium nutritional status could potentially confer benefits to patients with metabolic syndrome.

Porphyrin Derivative with Binary Properties of Photodynamic Therapy and Water-Dependent Reversible Photoacidity Therapy for Treating Hypoxic Tumor.

Porphyrin photosensitizers are the classic drugs in clinical photodynamic therapy (PDT), but the hypoxia of tumor environment and the rapid oxygen consumption of PDT severely weaken their therapeutic effect. A recently reported water-dependent reversible photoacidity therapy (W-RPAT) is O2-independence, providing a solution for the treatment of hypoxic tumors. In this work, TPP-O-PEG5, a porphyrin derivative with binary properties of PDT and W-RPAT, is designed and synthesized for the first time. The nanoparticles (NPs) of TPP-O-PEG5 encapsulated with DSPE-mPEG2000, an amphiphilic polymer approved by Food and Drug Administration, can simultaneously produce reactive oxygen species and H+ under irradiation of a 660 nm laser, and revert the H+ back under darkness, presenting strong phototoxicity to multiple tumor cell lines with no obvious difference between the IC50 values tested under normoxic (≈20% O2) and hypoxic (<0.5% O2) conditions. Excitingly, in vivo experiments show that the therapeutic effect of TPP-O-PEG5 NPs on large hypoxic tumors is better than that of NPe6, a clinical porphin PDT drug. This work provides a novel strategy for porphyrin photosensitizers to break through the limitation of hypoxic environment, and significantly improve the phototherapeutic effect on hypoxic tumors.

A compact multi-pixel superconducting nanowire single-photon detector array supporting gigabit space-to-ground communications.

Classical and quantum space-to-ground communications necessitate highly sensitive receivers capable of extracting information from modulated photons to extend the communication distance from near-earth orbits to deep space explorations. To achieve gigabit data rates while mitigating strong background noise photons and beam drift in a highly attenuated free-space channel, a comprehensive design of a multi-functional detector is indispensable. In this study, we present an innovative compact multi-pixel superconducting nanowire single-photon detector array that integrates near-unity detection efficiency (91.6%), high photon counting rate (1.61 Gcps), large dynamic range for resolving different photon numbers (1-24), and four-quadrant position sensing function all within one device. Furthermore, we have constructed a communication testbed to validate the advantages offered by such an architecture. Through 8-PPM (pulse position modulation) format communication experiments, we have achieved an impressive maximum data rate of 1.5 Gbps, demonstrating sensitivities surpassing previous benchmarks at respective speeds. By incorporating photon number information into error correction codes, the receiver can tolerate maximum background noise levels equivalent to 0.8 photons/slot at a data rate of 120 Mbps-showcasing a great potential for daylight operation scenarios. Additionally, preliminary beam tracking tests were conducted through open-loop scanning techniques, which revealed clear quantitative dependence indicating sensitivity variations based on beam location. Based on the device characterizations and communication results, we anticipate that this device architecture, along with its corresponding signal processing and coding techniques, will be applicable in future space-to-ground communication tasks.