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Zhengjun Huang,1,2 Zhouqian Jiang,1,2 Chengfei Zhao,1,2 Wendi Han,3 Liqing Lin,1,2 Ailin Liu,1,2 Shaohuang Weng,1,2 Xinhua Lin1,2 1Department of Pharmaceutical Analysis, School of Pharmacy, Fujian Medical University, 2Higher Educational Key Laboratory for Nano Biomedical Technology of Fujian Province, 3Department of Pharmacy, The First Affiliated Hospital of Fujian Medical University, Fuzhou, People’s Republic of China Abstract: Carbohydrate antigen 19-9 (CA19-9) is an important biomarker for the early diagnosis and clinical monitoring of pancreatic cancer. Reliable, simple, and accurate methods for the detection of CA19-9 are still urgently needed. In this study, polythionine-Au composites (AuNPs@PThi) were designed and prepared through one-pot reaction using HAuCl4 as the co-oxidant and raw material in thionine solution containing FeCl3 as the oxidant. AuNPs@PThi-immobilized glassy carbon electrode was used as a sensitive redox probe for electrochemical interface. AuNPs@PThi not only favored the amplification of electrochemical signals but also facilitated excellent environmental friendliness for bioassay. Maximizing the electrochemical properties of AuNPs@PThi, an effective label-free electrochemical immunoassay for the ultrasensitive and reliable detection of CA19-9 was developed. Under optimal conditions, the linear range of the proposed immunosensor was estimated to range from 6.5 to 520 U/mL, with a detection limit of 0.26 U/mL at a signal-to-noise ratio of 3. The prepared immunosensor for CA19-9 detection showed high sensitivity, stability, and reproducibility. Furthermore, the fabricated immunosensor based on AuNPs@PThi can effectively detect and distinguish clinical serum samples of pancreatic cancer and normal control with accuracy and convenience. Keywords: polythionine-Au composites, label-free electrochemical immunoassay, carbohydrate antigen 19-9, clinical sample, signal amplification

Chunling Wang,1 Xiaobo Cheng,2 Yuqing Su,1 Ying Pei,3 Yanzhi Song,1 Jiao Jiao,1 Zhenjun Huang,1 Yanfei Ma,1 Yinming Dong,1 Ying Yao,1 Jingjing Fan,1 Han Ta,1 Xinrong Liu,1 Hui Xu,1 Yihui Deng1 1College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Deli Wei Biological Technology Co, Ltd, Beijing, People’s Republic of China; 3Shenyang Women’s and Children’s Hospital, Shenyang, People’s Republic of China Abstract: The cross-administration of nanocarriers modified by poly(ethylene glycol) (PEG), named PEGylated nanocarriers, a type of combination therapy, is becoming an increasingly important method of long-term drug delivery, to decrease side effects, avoid multidrug resistance, and increase therapeutic efficacy. However, repeated injections of PEGylated nanocarriers induces the accelerated blood clearance (ABC) phenomenon, prevents long circulation, and can cause adverse effects owing to alterations in the biodistribution of the drug. Although the nature of the ABC phenomenon that is induced by repeated injections of PEGylated nanocarriers has already been studied in detail, there are few reports on the immune response elicited by the cross-administration of PEGylated nanocarriers. In this study, we investigated the ABC phenomenon induced by the intravenous cross-administration of various PEGylated nanocarriers, including PEGylated liposomes (PL), PEG micelles (PM), PEGylated solid lipid nanoparticles (PSLN), and PEGylated emulsions (PE), in beagle dogs. The results indicated that the magnitude of the immune response elicited by the cross-administration was in the following order (from the strongest to the weakest): PL, PE, PSLN, PM. It is specifically PEG in the brush structure that elicits a significant immune response, in both the induction phase and the effectuation phase. Furthermore, the present study suggests that there is a considerable difference between the effect of repeated injections and cross-administration, depending on the colloidal structure. This work is a preliminary investigation into the cross-administration of PEGylated nanocarriers, and our observations can have serious implications for the design of combination therapies that use PEGylated vectors. Keywords: ABC phenomenon, repeated injection, cross-administration, immune response, PEGylated nanocarriers

Yanzhi Song,1 Zhenjun Huang,1 Yang Song,2 Qingjing Tian,1 Xinrong Liu,1 Zhennan She,1 Jiao Jiao,1 Eliza Lu,3 Yihui Deng11College of Pharmacy, Shenyang Pharmaceutical University, Shenyang, People’s Republic of China; 2Jiangsu Hansoh Pharmaceutical Co., Ltd., Lianyungang, People’s Republic of China; 3Livzon Mabpharm Inc., Zhuhai, People’s Republic of ChinaAbstract: The applications of ethylenediaminetetraacetic acid (EDTA) have been expanded from the treatment of heavy metal poisoning to chelation therapies for atherosclerosis, heart disease, and cancers, in which EDTA reduces morbidity and mortality by chelating toxic metal ions. In this study, EDTA was used in a drug delivery system by adopting an NH4EDTA gradient method to load doxorubicin into liposomes with the goal of increasing therapeutic effects and decreasing drug-related cytotoxicity. The particle size of the optimum NH4EDTA gradient liposomes was 79.4±1.87 nm, and the entrapment efficiency was 95.54%±0.59%. In vitro studies revealed that liposomes prepared using an NH4EDTA gradient possessed long-term stability and delayed drug release. The in vivo studies also showed the superiority of the new doxorubicin formulation. Compared with an equivalent drug dose (5 mg/kg) prepared by (NH4)2SO4 gradient, NH4EDTA gradient liposomes showed no significant differences in tumor inhibition ratio, but cardiotoxicity and liposome-related immune organ damage were lower, and no drug-related deaths were observed. These results show that use of the NH4EDTA gradient method to load doxorubicin into liposomes could significantly reduce drug toxicity without influencing antitumor activity.Keywords: NH4EDTA, liposome, doxorubicin, ion gradient, antitumor activity, toxicity

BACKGROUND: B vitamins can effectively attenuate inflammatory and neuropathic pain in experimental animals, while their efficacy in treating clinical pain syndromes remains unclear. To understand possible mechanisms underlying B vitamin-induced analgesia and provide further evidence that may support the clinical utility of B vitamins in chronic pain treatment, this study investigated effects of thiamine (B1) on the excitability and Na currents of dorsal root ganglion (DRG) neurons that have been altered by nerve injury. METHODS: Nerve injury was mimicked by chronic compression of DRG in rats. Neuropathic pain was evidenced by the presence of thermal hyperalgesia. Intracellular and patch-clamp recordings were made in vitro from intact and dissociated DRG neurons, respectively. RESULTS: (1) In vivo intraperitoneal administration of B1 (66 mg/kg/day, 10-14 doses) significantly inhibited DRG compression-induced neural hyperexcitability, in addition to suppressing thermal hyperalgesia. (2) In vitro perfusion of B1 (0.1, 1 and 10 mM) resulted in a dose-dependent inhibition of DRG neuron hyperexcitability. In addition, the DRG neurons exhibited size-dependent sensitivity to B1 treatment, i.e., the small and the medium-sized neurons, compared to the large neurons, were significantly more sensitive. (3) Both in vitro (1 mM) and in vivo application of B1 significantly reversed DRG compression-induced down-regulation of tetrodotoxin-resistant but not tetrodotoxin-sensitive Na current density in the small neurons. B1 at 1 mM also reversed the compression-induced hyperpolarizing shift of the inactivation curve of the tetrodotoxin-resistant currents and the upregulated ramp currents in small DRG neurons. CONCLUSION: Thiamine can reduce hyperexcitability and lessen alterations of Na currents in injured DRG neurons, in addition to suppressing thermal hyperalgesia. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We examined the association between children's state of residence and their access to health care among specific types of immigrant families: foreign-born children, US-born children with 1 foreign-born parent, US-born children with both foreign-born parents, and nonimmigrant families. METHODS: We analyzed data from 12 400 children from the 2003 National Survey of Children's Health in the 6 states with the highest proportion of immigrants (California, Florida, Illinois, New York, New Jersey, and Texas). RESULTS: Multivariable analyses indicated that among foreign-born children, those living in California, Illinois, and Texas were more likely to lack access to health care compared with those living in New York. Among foreign-born children with 1 or 2 US-born parents, Texas children were most likely to lack health insurance. Within nonimmigrant families, children from California, Florida, and Texas had significantly more access and use problems. CONCLUSIONS: Our findings document differential health care access and use among states for specific immigrant family types. [ABSTRACT FROM AUTHOR]

Asian Americans (AA) are thought to have the lowest rates of substance use. This study examined substance use prevalence among 494 urban-dwelling Southeast Asians using snowball techniques. Prevalence estimates were age-adjusted proportionate to the U.S. Asian population. Findings show beer and alcohol consumption approximated the national percentage among 25-44 year olds. U.S.-born were about three times likelier to have past month substance use. Foreign-born Vietnamese were likelier than U.S.-born to use all substances except for beer. U.S.- and foreign-born beer consumption rates were similar. Future research is needed to delineate substance use determinants and patterns in foreign and U.S.-born AA sub-groups. [ABSTRACT FROM AUTHOR]

There is a growing awareness that internal migration in China might shift the HIV epidemic by broadening the social and sexual mixing of its population. However, little is known about how drug use/abuse might contribute to the spread of HIV. This qualitative study aims to elucidate factors for preventing substance abuse and HIV among two types of male migrants living in the Shanghai metropolitan area; the general migrant population and so-called 'money boys' (those who engaged in same-sex activities for money). Compared to most male migrants, the 'money boys' had a slightly better economic situation; rarely visited their hometowns; used alcohol less but drugs more; had more knowledge about HIV and sexually transmitted diseases; higher HIV/ STD testing rates and fewer HIV risk behaviors. The general male migrants had more misconceptions about HIV (e.g. the need to pay for HIV testing) than the 'money boys'. However, it was noted that 'money boys' who were new to the enterprise and men who have sex with men but did not engage in commercial sex often lacked HIV knowledge and protective skills. Given the needs of various sub-types of 'migrants', differential approaches to HIV prevention are needed. [ABSTRACT FROM AUTHOR]

OBJECTIVES: We examined the relation between parents' level of English proficiency and their children's access to health care. METHODS: Using the 2001 California Health Interview Survey, we conducted bivariate and multivariate analyses of several measures of children's access to health care (current health insurance status, usual source of care, emergency room visits, delayed or forgone care, traveling to another country for health care, and perceived discrimination in health care) and their association with parents' English proficiency. RESULTS: Compared with English-speaking households, children in non-English-speaking households were more likely to lack health insurance, to not have doctor contact, and to go to other countries for health care and were less likely to use emergency rooms. Their parents were less likely to report their children's experiencing delayed or forgone care or discrimination in health care. CONCLUSION: English proficiency is a strong predictor of access to health insurance for children, and children in non-English-speaking families are especially likely to rely on other countries for their health care. English proficiency may mitigate the effects of race/ethnicity commonly observed in health care access and utilization studies. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To examine the association between parental immigrant status and awareness of health and community resources to help address common family problems. METHODS: Using the 1999 National Survey of America's Families, a survey of the health, economic, and social characteristics of children and adults, bivariate and multivariate analyses were conducted on 35,938 children to examine the relationship between parents' immigrant status (U.S.-born citizens, naturalized citizens, and noncitizens) and their responses to questions about their awareness of specific health and community resources. RESULTS: Compared to U.S.-born citizens, noncitizens were at the highest risk of not being aware of health and community resources for most outcomes, followed by naturalized citizens. The services of which noncitizens were most likely to be unaware were places to get help for family discord, child care issues, and family violence. Multivariate analyses indicate that parental race/ethnicity, education level, employment status, and child age were other significant independent risk factors. CONCLUSIONS: Immigrant parents are at particularly high risk of alienation from systems of health care and support services that are available to low-income and other vulnerable populations in the United States. These findings clearly document disparate awareness among parents of different immigrant status. Community and health resources should reach out to immigrant populations, in linguistically and culturally appropriate ways, to alert them to the availability of their services. [ABSTRACT FROM AUTHOR]

BACKGROUND: The 'digital divide' is the gap between those with access to information tools such as the Internet and those without access. The gap has been described by income, education, age, and race. Little information exists on computer and Internet access and use for health information by parents, particularly among populations of low income and low education level. OBJECTIVE: To describe computer and Internet access and use, including health information retrieval, among low-income, urban, African American caregivers (parents). DESIGN: Cross-sectional survey administered in pediatric waiting rooms of urban community-based health centers in a low-income area. PARTICIPANTS: Caregivers of pediatric outpatients. MAIN OUTCOME MEASURES: Access to computers, Internet access, and use of Internet for health information. RESULTS: In 2003, among 260 African Americans who completed surveys, 58% had a computer and 41% had home Internet access. Fifty-two percent had used the Internet for finding health information. Ninety-three percent agreed or strongly agreed that there is useful health information on the Internet. Ninety-two percent agreed or strongly agreed that they would want to talk with a medical professional about health information on the Internet. Sixty-five percent of respondents had no additional schooling after high school. Annual household income was

OBJECTIVE: To examine the associations of sociodemographic characteristics with both the prevalence and the causes of delayed or forgone care in a nationally representative sample of children with special health care needs. METHODS: Data were abstracted from the 2001 National Survey of Children with Special Health Care Needs. The families of children with special health care needs (CSHCN) who reported delayed or forgone care were asked about the reasons. The 12 reasons in the questionnaire were grouped into 5 categories. Bivariate and multivariate logistic regression analyses were conducted in SUDAAN to examine the relationship between sociodemographic characteristics of CSHCN and the incidence of delayed or forgone care by its reasons. RESULTS: Nearly 10% of CSHCN had experienced delayed or forgone health care in the past 12 months in 2001. Logistic regression showed that delayed or forgone care was more likely to be reported by the families of CSHCN who were adolescents, who had more severe limitations, lived in the South or West, lacked medical insurance, and who lived in families under or near the federal poverty line. Hispanics were more likely to report 'lack of medical specialty' and 'had language, communication, or cultural problems with provider.' Both Hispanics and non-Hispanic others were twice as likely to report 'provider not accessible' as reasons for the delayed or forgone care compared with non-Hispanic whites or blacks. conclusion: CSHCN with certain socioeconomic status and sociodemographic characteristics, as well as those with severe limitations in activity, were more likely to be affected by circumstances that result in delayed or forgone care. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the association between the parent's language of interview and the access to care for children with special health care needs (CSHCN). METHODS: We used the 2001 National Survey of Children with Special Health Care Needs to compare socio-demographic characteristics and health care access variables among CSHCN with parents who interviewed in English and another language. Additional multivariate analyses explored the effect of language of interview on access to health care for the subgroup of Hispanic respondents. RESULTS: CSHCN with non-English-speaking parents were from less-educated and lower-income families and were more likely to lack insurance and have conditions that greatly affected their activities. These children were also more likely to have inadequate insurance (odds ratio [OR]=11.29), have an unmet need for family support services (OR=1.88), lack a personal doctor or nurse (OR=1.98), lack a usual source of care (OR=1.89), and lack family-centered care (OR=1.74). Non-English-speaking parents were more likely to report having employment consequences (OR=1.94) and spending over $500 out-of-pocket annually on the child's health care needs (OR=1.49). The likelihood of Hispanic children experiencing health care access barriers compared with non-Hispanic children was reduced when language was controlled for and several disparities between Hispanic children and other children became insignificant. CONCLUSIONS: CSHCN with non-English-speaking parents were more likely to be from disadvantaged families and to experience barriers to access than were CSHCN with English-speaking parents. Systems of care for CSHCN should consider the needs and challenges experienced by families whose primary language is not English. [ABSTRACT FROM AUTHOR]

OBJECTIVE: This study examines the health status and health services access and utilization characteristics of US Chinese, Asian Indian, Filipino, other Asian/Pacific Islander (API), and non-Hispanic white children by using nationally representative data. METHODS: We analyzed the aggregated data file from the National Health Interview Survey from 1997 to 2000 including 334 Chinese, 287 Asian Indian, 292 Filipino, 696 'other API,' and 29,016 non-Hispanic white children <18 years old. Bivariate and multivariate analyses were conducted to examine the relationship between Asian ethnicities and dependent variables including components of health status, health services access, and utilization. RESULTS: Logistic regression reveals that all Asian American children were less likely to miss school because of illness or injury or have learning disabilities compared with non-Hispanic whites. Other APIs were less likely to be taking prescription medication for at least 3 months, and Asian Indian children were half as likely to have chronic conditions. Chinese, Filipino, and other API children were more likely to be without contact with a health professional within the past 12 months. Citizenship/nativity status, maternal education attainment, and poverty status were all significant independent risk factors for health care access and utilization. CONCLUSIONS: Asian ethnicities and being foreign-born are generally associated with more favorable health status measures such as school absence, learning disability, use of prescription medications, and chronic conditions. However, these attributes are negatively associated with health care access and utilization, suggesting the need for outreach to Asian immigrant populations to educate them on accessing the US health care system. [ABSTRACT FROM AUTHOR]

ObjectiveTo examine the prevalence of herbal supplement use and its association with sociodemographic, health status, and health behavior characteristics in a nationally representative sample of US women.MethodsWe analyzed the cancer supplement file of the 2000 National Health Interview Survey, which included 11 888 non-Hispanic white, 2866 non-Hispanic black, 3035 Hispanic, and 599 non-Hispanic other women. Bivariate and multivariate analyses were conducted to examine the relationship between sociodemographic, health status, and health behavior characteristics and the use of: 1) any herbal supplement; 2) Echinacea, Ginkgo biloba, ginseng, or St. John's wort, and 3) at least 3 herbal supplements concurrently.ResultsNearly one-sixth of US women took at least 1 herbal supplement in 2000. Logistic regression showed that women who were non-Hispanic white, aged 35 to 64 years, more educated, not poor, current alcohol users, residents of the South and West, and who had functional limitations and chronic conditions were significantly more likely to take the most commonly reported herbal supplements.ConclusionOur study suggests high levels of herbal supplement use among US women. Supplement use is generally associated with higher education, higher income, residence in the South and West, and health needs. The growing practice of herbal supplement use suggests a need for public health guidance on the safe and efficacious use of these products. [ABSTRACT FROM AUTHOR]

PURPOSE: To examine the association of acculturation, as measured by language spoken at home, with the health, psychosocial, school, and parental risk factors of adolescents of various racial/ethnic groups. METHODS: Using the U.S. component of the 1997-98 World Health Organization Study of Health Behavior in School Children, bivariate and multiple logistic regression analyses were conducted of records for adolescents in four racial/ethnic groups to explore the relationship between the language spoken at home and outcome variables regarding health status and risks, psychosocial and school risk factors, and parental factors. Data were analyzed using Software for the Statistical Analysis of Correlated Data (SUDAAN). RESULTS: Adolescents of all racial and ethnic groups who primarily speak a language other than English at home are at elevated risk for psychosocial risk factors such as alienation from classmates and being bullied, and parental risk factors such as feeling that their parents are not able or willing to help them. Those who speak a combination of languages are also at risk for being bullied and for high parental expectations. Language spoken at home is generally not associated with health and safety measures for adolescents across racial/ethnic groups. CONCLUSIONS: Adolescents whose primary language at home is not English experience higher psychosocial, school, and parental risks than non-Hispanic white English-speakers. New immigrant youths of all races and ethnic groups would potentially benefit from preventive and risk-reduction services. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To examine the prevalence of vitamin-mineral supplement use and its association with sociodemographic, health status, and health behavior characteristics in a nationally representative sample of US women. METHODS: We analyzed the cancer supplement file of the 2000 National Health Interview Survey, which included 11,888 non-Hispanic white, 2866 non-Hispanic black, 3035 Hispanic, and 599 non-Hispanic other women. Bivariate and multivariate analyses were conducted to examine the relationships between sociodemographic, health status, and health behavior characteristics and the use of selected vitamin-mineral supplements. RESULTS: Nearly 60% of US women took at least one supplement in 2000. Logistic regression showed that women who were non-Hispanic white, married, older, more educated, not poor, former smokers, alcohol users, and regular exercisers were significantly more likely to take the most commonly reported vitamin-mineral supplements. Women who were obese or overweight and women who had not had contact with a health professional in the past 12 months were less likely to use supplements. CONCLUSION: Our study suggests high levels of vitamin-mineral supplement use among US women. Supplement use was generally associated with a healthier lifestyle and more resources. Our data suggest the need for public health education on the benefits of age- and health-appropriate use of supplements. [ABSTRACT FROM AUTHOR]

The study examined the association of language spoken at home with the school and health risks and behaviors of Asian American adolescents. Using the United States component of the 1997-1998 World Health Organization Study of Health Behavior in School Children, bivariate and multiple logistic regression analyses were conducted of records for Asian children to explore the relationship between language spoken at home and outcome variables regarding health behaviors, psychosocial and school risk factors, and parental factors. Compared to those who usually speak English at home, adolescents who usually speak another language, or who speak two languages equally, face a greater risk for health risk factors, psychosocial and school risk factors, and parental risk factors. Not speaking English at home was associated with higher health risks, including not wearing seat belts and bicycle helmets; higher psychosocial and school risk factors, including feeling that they do not belong at school, difficulty making new friends, and lacking confidence; and higher parental risks, including reporting that parents were not ready to help them or willing to talk to teachers. Adolescents less acculturated to the United States experience a variety of physical and psychosocial risks. School-based interventions such as early identification and outreach, needs assessment, and counseling and support services should be provided to immigrant students and their families. [ABSTRACT FROM AUTHOR]

Background and Aims: The prognosis and severity of hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) cannot be well-identified by serum biomarkers. The present study aims to determine the role of serum Golgi protein 73 (GP73) in predicting the prognosis and severity of liver necrotizing inflammation induced by HBV-ACLF., Methods: A total of 427 chronic HBV-infected patients were included for the present study. Among these patients, 179 patients had chronic hepatitis B (CHB), 96 patients had HBV-related liver cirrhosis (LC), and 152 patients had HBV-ACLF. The baseline and dynamic changes in serum GP73 levels were measured and compared in CHB, LC and HBV-ACLF patients., Results: The serum GP73 levels were significantly greater in HBV-ACLF patients when compared to CHB and LC patients. Furthermore, serum GP73 demonstrated excellent performance in distinguishing HBV-ACLF from CHB and LC, with an area under the curve of 0.969 and 0.824, respectively. In the logistic regression analysis, a high GP73 level was identified as an independent risk factor associated with death within 3 months, and the optimal cut-off level was 274.59 ng/mL. The serum GP73 levels significantly decreased and remained stable at approximately 6 months for survivors., Conclusion: Serum GP73 may serve as a valuable biomarker for the diagnosis and prognosis prediction of HBV-ACLF patients., (© 2024 The Author(s). Immunity, Inflammation and Disease published by John Wiley & Sons Ltd.)

The detection of cysteine (Cys) and homocysteine (Hcy) in biological fluids has great significance for early diagnosis, including Alzheimer's and Parkinson's disease. The simultaneous determination of Cys and Hcy with a single probe is still a huge challenge. To enlarge the differences in space structure (line and ring) and energy (-721.78 and -761.08 Hartree) between Cys and Hcy, and to cause a difference of aggregation kinetics, gold nanoparticles (AuNPs) are capped with hydrophilic and low-toxic polyvinylpyrrolidone (PVP) (named AuNPs@PVP) and some surface-active sites of AuNPs are masked, the active area for the binding between AuNPs and the detection object is confined, meanwhile, the stability of AuNPs is improved. A novel nanosensor based on confined active area and aggregation kinetics of AuNPs@PVP, is designed for the identification and determination of Cys and Hcy in 1 and 3 min, respectively, with sufficiently low detection limit (4.12 and 4.35 μM) and linear range (4.12-100 μM) for health evaluation. This single colorimetric sensor was applied successfully to the determination of urine and serum, evidencing high anti-interference ability., Competing Interests: Declarations. Competing interests: The authors declare no competing interests., (© 2025. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Covalent organic frameworks (COFs) hold promise in heterogeneous metal catalysis benefiting from their robust, crystalline, and porous structures. However, synthetic challenges persist in prolonged crystallization times, limited metal loading, and uncertain coordination environments. Here, we present the rapid crystallization and versatile metalation of new acetylhydrazone-linked COFs (AH-COFs) by condensation of ketone and hydrazide components, featuring full conversion within 30 min under open-air and mild conditions. The obtained AH-COFs exhibit exceptional thermal and chemical stability, maintaining high crystallinity and microporosity even under harsh conditions. This method shows the versatility of in situ metalation through subcomponent assembly with a wide range of metal centers, and the delicate control of coordination geometry through isoreticular functionalization for fine-tuning of the pore environments and metal catalytic activity. The metalated AH-COFs demonstrate excellent catalytic performance: AH-COF-2-Zn achieves high efficiency in CO 2 cycloaddition, while AH-COF-1-Cu-PSM achieves near-quantitative conversion in copper-catalyzed azide-alkyne cycloaddition (CuAAC) reactions, with both catalysts retaining their activity over multiple cycles. This study offers an efficient and versatile method for the rapid crystallization of designable, stable, and functional COFs, heading to practical applications prioritized on efficiency, scalability, and sustainability.

RNAs are central mediators of genetic information flow and gene regulation that underlie diverse cell types and cell states across species. Thus, methods that can sense and respond to RNA profiles in living cells will have broad applications in biology and medicine. CellREADR - Cell access through RNA sensing by Endogenous ADAR (adenosine deaminase acting on RNA), is a programmable RNA sensor-actuator technology that couples the detection of a cell-defining RNA to the translation of an effector protein to monitor and manipulate the cell. The CellREADR RNA device consists of a 5' sensor region complementary to a cellular RNA and a 3' protein payload coding region. Payload translation is gated by the removal of a STOP codon in the sensor region upon base pairing with the cognate cellular RNA through an ADAR-mediated A-to-I editing mechanism ubiquitous to metazoan cells. CellREADR thus represents a new generation of programmable RNA device for monitoring and manipulating animal cells in ways that are simple, versatile, and generalizable across tissues and species. Here, we describe a detailed procedure for implementing CellREADR experiments in cell culture systems and in animals. The procedure includes sensor and payload design, cloning, validation and characterization in mammalian cell cultures. The in vivo protocol focuses on AAV-based delivery of CellREADR through expression vectors using brain tissue as an example. We describe current best practices and various experimental controls., (Copyright © 2025. Published by Elsevier Inc.)

As modern communication and detection technologies advance at a swift pace, multifunctional electromagnetic interference (EMI) shielding materials with active/positive infrared stealth, hydrophobicity, and electric-thermal conversion ability have received extensive attention. Meeting the aforesaid requirements simultaneously remains a huge challenge. In this research, the melamine foam (MF)/polypyrrole (PPy) nanowire arrays (MF@PPy) were fabricated via one-step electrochemical polymerization. The hierarchical MF@PPy foam was composed of three-dimensional PPy micro-skeleton and ordered PPy nanowire arrays. Due to the upwardly grown PPy nanowire arrays, the MF@PPy foam possessed good hydrophobicity ability with a water contact angle of 142.00° and outstanding stability under various harsh environments. Meanwhile, the MF@PPy foam showed excellent thermal insulation property on account of the low thermal conductivity and elongated ligament characteristic of PPy nanowire arrays. Furthermore, taking advantage of the high conductivity (128.2 S m -1 ), the MF@PPy foam exhibited rapid Joule heating under 3 V, resulting in dynamic infrared stealth and thermal camouflage effects. More importantly, the MF@PPy foam exhibited remarkable EMI shielding effectiveness values of 55.77 dB and 19,928.57 dB cm 2  g -1 . Strong EMI shielding was put down to the hierarchically porous PPy structure, which offered outstanding impedance matching, conduction loss, and multiple attenuations. This innovative approach provides significant insights to the development of advanced multifunctional EMI shielding foams by constructing PPy nanowire arrays, showing great applications in both military and civilian fields., Competing Interests: Declarations. Conflict of interest: The authors declare no interest conflict. They have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024. The Author(s).)

Simulating the changes in ecosystem service value induced by land use changes in the peak cluster depression basin of southwestern Guangxi under multiple scenarios is of great importance for ensuring ecological security in the basin and enhancing regional ecosystem service value capabilities. Based on the CA-Logistic-Markov model, the land use of the study area was simulated under natural development, food security, and ecological protection scenarios in 2030. The ecosystem service value was calculated under each scenario using the equivalent factor correction model, and the spatiotemporal dynamic characteristics of the ecosystem service value in the peak cluster depression basin of southwestern Guangxi were quantitatively analyzed. The results showed as follows： ① Compared with the current situation of land use in 2020 and the predicted simulated land use in 2020, the standard Kappa index was 0.917, the location Kappa index was 0.952, and the numerical Kappa index was 0.958. In the simulation of the land use pattern of the peak cluster basin in southwest Guangxi in 2030, the CA-Markov model had high accuracy and reference-ability. ② Ecosystem service values in the study area for the periods 2000-2020 were 270.881 billion, 275.78 billion, and 278.332 billion yuan, indicating an overall upward trend. ③ The value of ecosystem services in the natural development, the food security, and the ecological protection scenarios was 282 138 million, 273 206 million, and 284 143 million, respectively. The study area exhibited a spatial distribution of ecosystem service values with higher values in the northwest and lower values in the southeast. In comparison to that in 2020, the ecosystem service value significantly decreased under the food security scenario, reflecting ecosystem degradation. Meanwhile, ecosystem service values increased under the natural development and ecological protection scenarios, signifying an improvement in ecological environmental quality. ④ Ecosystem service value hot spots and cold spots with high confidence had strong clustering and the hot spots were mainly concentrated in the northwestern mountainous area, whereas the cold spots with high confidence were mainly distributed in the southeastern plain area of the study area. The research results revealed the spatiotemporal pattern of land use change and ecosystem service value in the peak cluster depression basin of southwestern Guangxi under multiple scenarios, which can provide scientific basis for optimizing land use structure and spatial pattern and enhancing ecosystem services.

Methods that provide specific, easy, and scalable experimental access to animal cell types and cell states will have broad applications in biology and medicine. CellREADR - Cell access through RNA sensing by Endogenous ADAR (adenosine deaminase acting on RNA), is a programmable RNA sensor-actuator technology that couples the detection of a cell-defining RNA to the translation of an effector protein to monitor and manipulate the cell. The CellREADR RNA device consists of a 5' sensor region complementary to a cellular RNA and a 3' payload coding region; payload translation is gated by the removal of a STOP codon in the sensor region upon base pairing with the cognate cellular RNA through an ADAR-mediated A- to-I editing mechanism ubiquitous to metazoan cells. CellREADR thus highlights the potential for RNA-based monitoring and manipulation of animal cells in ways that are simple, versatile, and generalizable across tissues and species. Here, we describe a detailed protocol for implementing CellREADR experiments in cell cultures and in animals. The procedure includes sensor and payload design, cloning, validation and characterization in mammalian cell cultures. The in vivo animal protocol focuses on AAV-based delivery of CellREADR using brain tissue as examples. We describe current best practices, various experimental controls and trouble-shooting steps. Beginning from sensor design, the validation of RNA sensor-actuators in cell cultures can be completed in 2-3 weeks. The construction of AAV vectors and their in vivo validation and characterization will take additional 6-8 weeks.

Epigallocatechin-3-gallate (EGCG), a catechin present in green tea, has been studied extensively for its potential as a cosmetic ingredient due to its various biological properties. However, the low stability and bioavailability of EGCG have hindered its effective utilization in cosmetic applications. This study, to improve the stability and bioavailability of EGCG for reversing skin photo-aging, nonapeptide-1-conjugated mesoporous silica nanoparticles (EGCG@NP-MSN) were fabricated to load EGCG. MSNs can regulate the EGCG release and provide ultraviolet light (UV) protection to possess excellent photostability. Nonapeptide-1 exhibits melanin transfer interference properties and reduces the melanin content in treated skin areas. In vitro and in vivo results confirmed that the EGCG-loaded MSNs retained antioxidant properties, effectively scavenged the melanin and significantly reduced the deoxyribonucleic acid (DNA) damage in skin cells exposed to UV irradiation. The melanin inhibition rate is 5.22 times and the tyrosinase inhibition rate is 1.57 times that of free EGCG. The utilization of this innovative platform offers the potential for enhanced stability, controlled release, and targeted action of EGCG, thereby providing significant advantages for skin application.This delivery system combines the advantages of antioxidant, anti-aging, and anti-UV radiation properties, paving the way for the cosmetics development with improved efficacy and better performance in promoting skin health and appearance., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Meningeal metastasis (LM) is commonly seen in the advanced stages of cancer patients, often leading to a rapid decline in survival time and quality of life. Currently, there is still a lack of standardized treatments. Oncolytic viruses (OVs) are a class of emerging cancer therapeutics with the advantages of selectively replicating in cancer cells, delivering various eukaryotic transgenes, inducing immunogenic cell death, and promoting anti-tumor immunity. Some studies applying OVs intrathoracically or intraperitoneally for the treatment of malignant pleural and peritoneal effusions have shown promising therapeutic effects. If OVs could be applied to treat LM, it would bring significant survival benefits to patients with LM. In this review, we analyzed past research on the use of viruses to treat meningeal metastasis, summarized the efficacy and safety demonstrated by the research results, and analyzed the feasibility of oncolytic virus therapy for meningeal metastasis. We also summarized the existing data to provide guidance for the development of OVs that can be injected into the cerebrospinal fluid (CSF)., (© 2024. The Author(s).)

The coordination of forelimb and orofacial movements to compose an ethological reach-to-consume behavior likely involves neural communication across brain regions. Leveraging wide-field imaging and photo-inhibition to survey across the cortex, we identified a cortical network and a high-order motor area (MOs-c), which coordinate action progression in a mouse reach-and-withdraw-to-drink (RWD) behavior. Electrophysiology and photo-inhibition across multiple projection neuron types within the MOs-c revealed differential contributions of pyramidal tract and corticothalamic (CT MOs ) output channels to action progression and hand-mouth coordination. Notably, CT MOs display sustained firing throughout RWD sequence and selectively enhance RWD-relevant activity in postsynaptic thalamus neurons, which also contribute to action coordination. CT MOs receive converging monosynaptic inputs from forelimb and orofacial sensorimotor areas and are reciprocally connected to thalamic neurons, which project back to the cortical network. Therefore, motor cortex corticothalamic channel may selectively amplify the thalamic integration of cortical and subcortical sensorimotor streams to coordinate a skilled motor sequence., Competing Interests: DECLARATION OF INTERESTS The authors declare no competing interests.

The sensorimotor cortex participates in diverse functions with different reciprocally connected subregions and projection-defined pyramidal neuron types therein, while the fundamental organizational logic of its circuit elements at the single-cell level is still largely unclear. Here, using mouse Cre driver lines and high-resolution whole-brain imaging to selectively trace the axons and dendrites of cortical pyramidal tract (PT) and intratelencephalic (IT) neurons, we reconstructed the complete morphology of 1,023 pyramidal neurons and generated a projectome of 6 subregions within the sensorimotor cortex. Our morphological data revealed substantial hierarchical and layer differences in the axonal innervation patterns of pyramidal neurons. We found that neurons located in the medial motor cortex had more diverse projection patterns than those in the lateral motor and sensory cortices. The morphological characteristics of IT neurons in layer 5 were more complex than those in layer 2/3. Furthermore, the soma location and morphological characteristics of individual neurons exhibited topographic correspondence. Different subregions and layers were composed of different proportions of projection subtypes that innervate downstream areas differentially. While the axonal terminals of PT neuronal population in each cortical subregion were distributed in specific subdomains of the superior colliculus (SC) and zona incerta (ZI), single neurons selectively innervated a combination of these projection targets. Overall, our data provide a comprehensive list of projection types of pyramidal neurons in the sensorimotor cortex and begin to unveil the organizational principle of these projection types in different subregions and layers., Competing Interests: Competing interests: The authors declare that they have no competing interests., (Copyright © 2024 Mei Yao et al.)

Homeostatic plasticity maintains the stability of functional brain networks. The axon initial segment (AIS), where action potentials start, undergoes dynamic adjustment to exert powerful control over neuronal firing properties in response to network activity changes. However, it is poorly understood whether this plasticity involves direct synaptic input to the AIS. Here, we show that changes of GABAergic synaptic input from chandelier cells (ChCs) drive homeostatic tuning of the AIS of principal neurons (PNs) in the prelimbic (PL) region, while those from parvalbumin-positive basket cells do not. This tuning is evident in AIS morphology, voltage-gated sodium channel expression, and PN excitability. Moreover, the impact of this homeostatic plasticity can be reflected in animal behavior. Social behavior, inversely linked to PL PN activity, shows time-dependent alterations tightly coupled to changes in AIS plasticity and PN excitability. Thus, AIS-originated homeostatic plasticity in PNs may counteract deficits elicited by imbalanced ChC presynaptic input at cellular and behavioral levels.

Despite the great potential of starving therapy caused by nanoreactor based on glucose oxidase (GOX) in tumor therapy, efficiency and uncontrolled reaction rates in vivo lead to inevitable toxicity to normal tissues, which seriously hindering their clinical conversion. Herein, a cascade nanoreactor (GOX/Mn/MPDA) was constructed by coating mesoporous polydopamine nanoparticles (MPDA) with MnO 2 shell and then depositing GOX into honeycomb-shaped manganese oxide nanostructures to achieve a combination of ferroptosis, photothermal therapy and starving therapy. Upon uptake of nanodrugs to cancer cells, the MnO 2 shell would deplete glutathione (GSH) and produce Mn 2+ , while a large amount of H 2 O 2 generated from the catalytic oxidation of glucose by GOX would accelerate the Fenton-like reaction mediated by Mn 2+ , producing high toxic •OH. More importantly, the cascade reaction between GOX and MnO 2 would be further strengthened by localized hyperthermia caused by irradiated by near-infrared laser (NIR), inducing significant anti-tumor effects in vitro and in vivo. Regarding the effectiveness of tumor treatment in vivo, the tumor inhibition rate achieved an impressive 64.33%. This study provided a new strategy for anti-tumor therapeutic by designing a photothermal-enhanced cascade catalytic nanoreactor., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)