An Immunomodulatory Hydrogel by Hyperthermia-Assisted Self-Cascade Glucose Depletion and ROS Scavenging for Diabetic Foot Ulcer Wound Therapeutics.

Current therapeutic protocols for diabetic foot ulcers (DFUs), a severe and rapidly growing chronic complication in diabetic patients, remain nonspecific. Hyperglycemia-caused inflammation and excessive reactive oxygen species (ROS) are common obstacles encountered in DFU wound healing, often leading to impaired recovery. These two effects reinforce each other, forming an endless loop. However, adequate and inclusive methods are still lacking to target these two aspects and break the vicious cycle. This study proposes a novel approach for treating DFU wounds, utilizing an immunomodulatory hydrogel to achieve self-cascade glucose depletion and ROS scavenging to regulate the diabetic microenvironment. Specifically, AuPt@melanin-incorporated (GHM3) hydrogel dressing is developed to facilitate efficient hyperthermia-enhanced local glucose depletion and ROS scavenging. Mechanistically, in vitro/vivo experiments and RNA sequencing analysis demonstrate that GHM3 disrupts the ROS-inflammation cascade cycle and downregulates the ratio of M1/M2 macrophages, consequently improving the therapeutic outcomes for dorsal skin and DFU wounds in diabetic rats. In conclusion, this proposed approach offers a facile, safe, and highly efficient treatment modality for DFUs.

Simultaneous cortex-wide fluorescence Ca2+ imaging and whole-brain fMRI.

Achieving a comprehensive understanding of brain function requires multiple imaging modalities with complementary strengths. We present an approach for concurrent widefield optical and functional magnetic resonance imaging. By merging these modalities, we can simultaneously acquire whole-brain blood-oxygen-level-dependent (BOLD) and whole-cortex calcium-sensitive fluorescent measures of brain activity. In a transgenic murine model, we show that calcium predicts the BOLD signal, using a model that optimizes a gamma-variant transfer function. We find consistent predictions across the cortex, which are best at low frequency (0.009-0.08 Hz). Furthermore, we show that the relationship between modality connectivity strengths varies by region. Our approach links cell-type-specific optical measurements of activity to the most widely used method for assessing human brain function.

Values of applying white blood cell counts in the prognostic evaluation of resectable colorectal cancer.

The count and classification of white blood cells (WBCs) may be used as prognostic markers in certain types of cancer. The present study investigated the prognostic potential of the counts of WBCs, including lymphocytes (LYs), monocytes (MOs), neutrophils (NEs), eosinophils (EOs) and basophils (BAs), in the prognosis of resectable colorectal cancer. The present study recruited 153 resectable colorectal cancer cases retrospectively, which were pathologically confirmed. All patients were divided into two groups, according to the median value of LY (low LY, ≤1.632x109/l or high LY, >1.632x109/l), MO (low MO, ≤0.330x109/l or high MO, >0.330x109/l), NE (low NE, ≤3.600x109/l or high NE, >3.600x109/l), EO (low EO, ≤0.085x109/l or high EO, >0.085x109/l), BA (low BA, ≤0.010x109/l or high BA, >0.010x109/l), or WBC (low WBC, ≤5.780x109/l or high WBC, >5.780x109/l). To evaluate the alterations in WBC counts following surgery and adjuvant chemotherapy; all samples received oxiplatin and capecitabine (XELOX) for 6­8 cycles or 5­fluorouracil, leucovorin and oxaliplatin (mFOLFOX6) for 10­12 cycles. XELOX included oxaliplatin administered intravenously at a dose of 130 mg/m2 on day 1 and 850­1,250 mg/m2 capecitabine twice daily for days 1­14, repeated every 3 weeks. mFOLFOX6 included oxaliplatin administered intravenously at a dose of 85 mg/m2, 400 mg/m2 leucovorin and 400 mg/m2 5­FU on day 1 followed by 1,200 mg/m2/days continuous infusion for 2 days (in total, 2,400 mg/m2 over 46­48 h), repeated every 2 weeks. The present study investigated the post/pre­treatment of LY, MO, NE, EO, BA and WBC ratios (≤1 indicated that LY, MO, NE, EO, BA and WBC counts were not increased following therapy; whereas, >1 suggested increased counts). Kaplan­Meier curves were constructed to demonstrate overall survival (OS). A multivariate and univariate logistic regression analyses model was employed to identify the independent risk factors. Low pre­treatment BA counts were associated with larger tumor size (>5 cm); pre­treatment BA levels were positively associated with OS. Surgery significantly decreased the count of BAs and increased the count of EOs; whereas, no effect was observed on LYs, MOs, NEs or WBCs. Adjuvant chemotherapy markedly decreased the counts of LY, NE and WBC; whereas, no notable effects on MOs, EOs or BAs were observed. Whole course treatment (surgery combined with adjuvant chemotherapy) significantly decreased the values of LY, NE and WBC; however, increased the value of EO; no effects on the MO or BA counts were observed. An increased post­/pre­treatment NE ratio suggested poorer prognosis. Multivariate Cox regression analysis revealed that sex, tumor size, pre­treatment BA count and the post­/pre­treatment NE ratio were independent prognostic factors affecting OS. The results of the present study suggested that the pre­treatment BA count and post­/pre­treatment NE ratio may be potential prognostic factors for resectable colorectal cancer.