Minimally-invasive implantable device enhances brain cancer suppression.

Current brain tumor treatments are limited by the skull and BBB, leading to poor prognosis and short survival for glioma patients. We introduce a novel minimally-invasive brain tumor suppression (MIBTS) device combining personalized intracranial electric field therapy with in-situ chemotherapeutic coating. The core of our MIBTS technique is a wireless-ultrasound-powered, chip-sized, lightweight device with all functional circuits encapsulated in a small but efficient "Swiss-roll" structure, guaranteeing enhanced energy conversion while requiring tiny implantation windows ( ~ 3 × 5 mm), which favors broad consumers acceptance and easy-to-use of the device. Compared with existing technologies, competitive advantages in terms of tumor suppressive efficacy and therapeutic resolution were noticed, with maximum ~80% higher suppression effect than first-line chemotherapy and 50-70% higher than the most advanced tumor treating field technology. In addition, patient-personalized therapy strategies could be tuned from the MIBTS without increasing size or adding circuits on the integrated chip, ensuring the optimal therapeutic effect and avoid tumor resistance. These groundbreaking achievements of MIBTS offer new hope for controlling tumor recurrence and extending patient survival.

Trehalose enhanced cold atmospheric plasma-mediated cancer treatment.

Cold atmospheric plasma (CAP) is a unique form of physical plasma that has shown great potential for cancer therapy. CAP uses ionized gas to induce lethal oxidative stress on cancer cells; however, the efficacy of CAP therapy continues to be improved. Here, we report an injectable hydrogel-mediated approach to enhance the anti-tumor efficacy of CAP by regulating the phosphorylation of eIF2α. We discovered that reactive oxygen and nitrogen species (ROS/RNS), two main anti-tumor components in CAP, can lead to lethal oxidative stress on tumor cells. Elevated oxidative stress subsequently induces eIF2α phosphorylation, a pathognomonic marker of immunogenic cell death (ICD). Trehalose, a natural disaccharide sugar, can further enhance CAP-induced ICD by elevating the phosphorylation of eIF2α. Moreover, injectable hydrogel-mediated delivery of CAP/trehalose treatment promoted dendritic cell (DC) maturation, initiating tumor-specific T-cell mediated anti-tumor immune responses. The combination therapy also supported the polarization of tumor-associated macrophages to an M1-like phenotype, reversing the immunosuppressive tumor microenvironment and promoting tumor antigen presentation to T cells. In combination with immune checkpoint inhibitors (i.e., anti-programmed cell death protein 1 antibody, aPD1), CAP/trehalose therapy further inhibited tumor growth. Importantly, our findings also indicated that this hydrogel-mediated local combination therapy engaged the host systemic innate and adaptive immune systems to impair the growth of distant tumors.

Ultrasensitive FET biosensor chip based on self-assembled organic nanoporous membrane for femtomolar detection of Amyloid-ß.

Early diagnosis of Alzheimer's disease (AD) is critical for preventing disease progression, however, the diagnosis of AD remains challenging for most patients due to limitations of current sensing technologies. A common pathological feature found in AD-affected brains is the accumulation of Amyloid-ß (Aß) polypeptides, which lead to neurofibrillary tangles and neuroinflammatory plaques. Here, we developed a portable ultrasensitive FET biosensor chip based on a self-assembled nanoporous membrane for ultrasensitive detection of Aß protein in complex environments. The microscale semiconductor channel was covered with a self-assembled organic nanoporous membrane modified by antibody molecules to pick up and amplify the Aß protein signal. The nanoporous structure helps protect the sensitive channel from non-target proteins and improves its stability since no chemical functionalization process involved, largely reduces background noise of the sensing platform. When a bio-gated target is captured, the doping state of the polymer bulk could be tuned and amplified the strength of the weak signal, achieving ultrasensitive detecting performance (enabling the device to detect target protein less than 1 fg/ml in 1 µl sample). Moreover, the device simplifies the circuit connection by integrating all the connections on a 2 cm × 2 cm chip, avoiding expensive and complex manufacturing processes, and makes it usable for portable prognosis. We believe that this ultrasensitive, portable, low-cost Aß sensor chip shows the great potential in the early diagnosis of AD and large-scale population screening applications.

Injectable cold atmospheric plasma-activated immunotherapeutic hydrogel for enhanced cancer treatment.

Despite the promise of immune checkpoint blockade (ICB) for cancer treatment, challenges associated with this therapy still exist, including low response rates and severe side effects in patients. Here, we report a hydrogel-mediated combination therapy for enhanced ICB therapy. Specifically, cold atmospheric plasma (CAP), an ionized gas consisting of therapeutically effective reactive oxygen species (ROS) and reactive nitrogen species (RNS), can effectively induce cancer immunogenic cell death, releasing tumor-associated antigens in situ and initiating anti-tumor immune responses, which, therefore, can synergistically augment the efficacy of immune checkpoint inhibitors. To minimize the systemic toxicity of immune checkpoint inhibitors and improve the tissue penetration of CAP, an injectable Pluronic hydrogel was employed as a delivery method. Our results show that major long-lived ROS and RNS in CAP can be effectively persevered in Pluronic hydrogel and remain efficacious in inducing cancer immunogenic cell death after intratumoral injection. Our findings suggest that local hydrogel-mediated combination of CAP and ICB treatment can evoke both strong innate and adaptive, local and systemic anti-tumor immune responses, thereby inhibiting both tumor growth and potential metastatic spread.

Additional health education and nutrition management cause more weight loss than concurrent training in overweight young females.

OBJECTIVE: This study aimed to compare the effect of concurrent training and the addition of health education and nutrition management on body composition and health-related outcomes. METHODS: Twenty-four healthy overweight females (20.42 ± 1.02 years, body mass index [BMI] 25.83 ± 3.63 kg∙m-2) were assigned to a concurrent training group (Exe, n = 12) or a concurrent training and health education group (Exe + Edu, n = 12). Both groups completed 8 weeks of concurrent training (6 days/week), whereas the Exe + Edu participants received additional health education and controlled daily energy intake within the basal metabolic rate. Body composition, serum glucose, lipids and related hormones were measured before and after intervention. RESULTS: After intervention, the Exe group lost 2.47 kg (±2.46) of body mass, 2.44 kg (±1.71) of total fat mass (FM), corresponding to a body fat percentage (BF%) of 2.25%. Losses of body mass, total FM and BF% in the Exe + Edu group were -5.19 ± 1.87 kg, -4.42 ± 1.83 kg and -4.33 ± 2.39%, respectively. The Exe + Edu participants had significantly greater reductions of body mass, total FM, and trunk and leg FM relative to the Exe participants (p < 0.05). Serum glucose, lipids, insulin and progesterone levels were improved in both groups without group difference. CONCLUSION: Concurrent training is an effective short-term training strategy for reducing FM and improving fasting glucose, blood lipids and related hormones. Furthermore, the combination of additional health education can achieve greater effects on weight loss and the reduction of total and regional FM, which may be a better obesity treatment method.

Advances in microneedles for non-transdermal applications.

INTRODUCTION: Microneedles (MNs) have emerged as a promising tool for various therapeutic and diagnostic applications. While MNs have been prominently used for transdermal applications, recent advances in materials science, microfabrication technologies, and clinical devices enable the expansion of MNs to diverse non-transdermal applications. AREAS COVERED: This review provides an overview of recent advances in the MN technology for non-transdermal applications. The classification of MNs and their applications to ocular, vascular, oral, mucosal, and cancer tissues are particularly highlighted. EXPERT OPINION: Recent efforts in MN designs have enabled and broadened MNs to many non-transdermal applications. It is anticipated to witness many new MN-mediated non-transdermal applications in the near future. By advancing MN systems with suitable properties for target tissues, it is possible to achieve high drug delivery efficiency that outperforms traditional drug delivery methods. Further endeavors in translation and commercialization of these novel technologies are equally critical.

Association of breastfeeding and postmenopausal osteoporosis in Chinese women: a community-based retrospective study.

BACKGROUND: Postmenopausal osteoporosis (PMOP) has long been a pervasive public health concern. With the aging Chinese population, the prevention, assessment and management of postmenopausal osteoporosis were particularly important. During the breastfeeding, a large amount of Calcium loss from maternal bone for infants' growth. However, whether this loss is completely reversible remains controversial. As the relationship between breastfeeding and postmenopausal osteoporosis is different from society to society and is not clear from the literature, the purpose of this study was to determine whether breastfeeding was an independent factor for the development of PMOP based on Chinese postmenopausal population. METHODS: A retrospective cross-sectional investigation was conducted at Tianjin Xiaobailou health Community Healthcare Center between December 2017 and June 2018. Postmenopausal women over the age of 50 who underwent the annual health examination or visited the center to perform bone densitometry as a part of routine screening for disease were recruited. A trained community nurse administered a questionnaire to all participants by face-to-face interview. Participants were questioned about age, BMI, Vitamin D and calcium intake, the history of smoking, drinking and fracture, age of menarche, age of menopause, the number of pregnancy, parity, feeding pattern (breastfeeding, artificial feeding and mixed feeding) and overall breastfeeding duration. BMD measurements were carried out using quantitative ultrasound (QUS) at the bilateral radius. RESULTS: A total of 202 women who met the inclusive and exclusive criteria were enrolled. Univariate analysis revealed that overall breastfeeding more than 24 months increased the risk of osteoporosis (OR 39.00, 95%CI 2.40-634.65, p = 0.010). However, multivariate estimate of the risk of osteoporosis by overall breastfeeding duration suggested that when controlling for age, BMI, the number of pregnancy and parity, the overall breastfeeding duration was not an independent risk factor for postmenopausal osteoporosis (OR 5.22, 95%CI 0.18-147.76, p = 0.333). Additionally, age (OR 1.16, 95%CI 1.05-1.29, p = 0.003), BMI (OR 1.26, 95%CI 1.04-1.54, p = 0.021) and the number of pregnancy (OR 1.80, 95%CI 1.08-2.98, p = 0.024) were significant associated with postmenopausal osteoporosis. CONCLUSION: Breastfeeding was not associated with postmenopausal osteoporosis, while age, BMI and the number of pregnancy may contribute to increasing risk of postmenopausal osteoporosis in Chinese women.

The prognostic impact of decreased pretreatment haemoglobin level on the survival of patients with lung cancer: a systematic review and meta-analysis.

BACKGROUND: Many studies have reported the prognostic value of haemoglobin level for cancers. Whereas the prognostic impact of decreased pretreatment haemoglobin level on the survival of patients with lung cancer remains controversial, herein, a systematic review and meta-analysis were conducted to investigate whether a decreased haemoglobin level before treatment is a significant predictor of survival in patients with lung cancer. METHODS: We performed a systematic review and meta-analysis of observational studies to evaluate the prognostic impact of a decreased haemoglobin level on the survival of patients with lung cancer. Relevant studies were retrieved from databases including PubMed, Embase, Web of Science and the Cochrane Library. Reference lists were hand-searched for potentially eligible studies. The Newcastle-Ottawa scale was used to assess the quality of included studies. Observational studies were included if they provided sufficient information for the extraction of the pooled hazard ratios (HR) and 95% confidence intervals (95% CI) for overall survival, disease-free survival, relapse-free survival, progression-free survival, event-free survival and time to progression. Subgroup analysis, meta-regression and sensitivity analyses were applied to explain the heterogeneity. RESULTS: Fifty-five articles involving a total of 22,719 patients were obtained to evaluate the correlation between haemoglobin level and survival. The results indicated that decreased haemoglobin level was significantly associated with poor overall survival of patients with lung cancer (HR 1.51, 95% CI 1.42-1.61), both in non-small cell lung cancer (HR 1.57, 95% CI 1.44-1.72) and in small cell lung cancer (HR 1.56, 95% CI 1.21-2.02). We also found that the lower the haemoglobin level, the shorter was the overall survival of patients with lung cancer (HR 1.11, 95% CI 1.06-1.16). However, the relationship between decreased haemoglobin and relapse-free survival was not significant (HR 1.37, 95% CI 0.91-2.05). CONCLUSION: A decreased pretreatment haemoglobin level among patients with lung cancer is a prognostic factor of poor survival that can serve as an important indicator in survival prediction, risk stratification and treatment selection. In clinical practice, more attention should be paid to monitoring pretreatment haemoglobin levels among patients with lung cancer.