A pH responsive, chitosan‐based hydrogel film is used to cap the pores of a porous SiO2 layer. The porous SiO2 layer is prepared by thermal oxidation of an electrochemically etched Si wafer, and the hydrogel film is prepared by reaction of chitosan with glycidoxypropyltrimethoxysilane (GPTMS). Optical reflectivity spectroscopy and scanning electron microscopy (SEM) confirm that the bio‐polymer only partially infiltrates the porous SiO2 film, generating a double layer structure. The optical reflectivity spectrum displays Fabry–Pérot interference fringes characteristic of a double layer, which is characterized using reflective interferometric Fourier transform spectroscopy (RIFTS). Monitoring the position of the RIFTS peak corresponding to the hydrogel layer allows direct, real‐time observation of the reversible volume phase transition of the hydrogel upon cycling of pH in the range 6.0–7.4. The swelling ratio and response time are controlled by the relative amount of GPTMS in the hydrogel. The pH‐dependent volume phase transition can be used to release insulin trapped in the porous SiO2 layer underneath the hydrogel film. At pH 7.4, the gel in the top layer effectively blocks insulin release, while at pH 6.0 insulin penetrates the swollen hydrogel layer, resulting in a steady release into solution.

For appropriate selection of antibiotics in the treatment of pathogen infection, rapid antibiotic susceptibility testing (AST) is urgently needed in clinical practice. This study reports the utilization of a microfluidic pH sensor for monitoring bacterial growth rate in culture media spiked with different kinds of antibiotics. The microfluidic pH sensor was fabricated by integration of pH-sensitive chitosan hydrogel with poly(dimethylsiloxane) (PDMS) microfluidic channels. For facilitating the reflectometric interference spectroscopic measurements, the chitosan hydrogel was coated on an electrochemically etched porous silicon chip, which was used as the substrate of the microfluidic channel. Real-time observation of the pH change in the microchannel can be realized by Fourier transform reflectometric interference spectroscopy (FT-RIFS), in which the effective optical thickness (EOT) was selected as the optical signal for indicating the reversible swelling process of chitosan hydrogel stimulated by pH change. With this microfluidic pH sensor, we demonstrate that confinement of bacterial cells in a nanoliter size channel allows rapid accumulation of metabolic products and eliminates the need for long-time preincubation, thus reducing the whole detection time. On the basis of this technology, the whole bacterial growth curve can be obtained in less than 2 h, and consequently rapid AST can be realized. Compared with conventional methods, the AST data acquired from the bacterial growth curve can provide more detailed information for studying the antimicrobial behavior of antibiotics during different stages. Furthermore, the new technology also provides a convenient method for rapid minimal inhibition concentration (MIC) determination of individual antibiotics or the combinations of antibiotics against human pathogens that will find application in clinical and point-of-care medicine.

Noninvasive and visual monitoring of glucose is highly desirable for diabetes diagnostics and long-term home-based health management. Owing to the correlation of the glucose level between blood and sweat, on-body sweat glucose detection provides potential for noninvasive healthcare but is highly challenging. Herein, we for the first time demonstrate a wearable skin pad based on the ratiometric fluorescent nanohybrid, which can realize noninvasive and visual monitoring of sweat glucose. Luminescent porous silicon (PSi) particles, which have a porous structure and oxidation-responsive photoluminescence decay, are chosen to load (adsorb or entrap) carbon quantum dots (CQDs) for the construction of the dual fluorescence nanohybrid. Bimetallic (Au and Ag) nanoparticles (BiM) are also co-decorated on the PSi particle to improve detection sensitivity by enhancing PSi's initial fluorescence and oxidation kinetics. Owing to the efficient fluorescence resonance energy transfer effect, BiM-CQDs@PSi initially exhibits PSi's red fluorescence with complete quenching of CQDs's blue fluorescence. The oxidation of PSi triggered by hydrogen peroxide (H 2 O 2 ) weakens the FRET effect and decays PSi's fluorescence, causing ratiometric fluorescence to change from red (PSi) to blue (CQDs). A wearable skin pad is easily fabricated by co-immobilization of BiM-CQDs@PSi and glucose oxidase (GOX) in a transparent and biocompatible chitosan film supported by an adhesive polyurethane membrane. When the skin pad is attached on the body, the same ratiometric fluorescence transition (red → blue) is observed upon the stimulation of H 2 O 2 generated in GOX-catalyzed oxidation of sweat glucose. Based on the strong correlation between the ratio of the fluorescence change and sweat glucose level, clinical tests toward diabetics and healthy volunteers can clearly indicate hyperglycemia.

Neoadjuvant chemotherapy is a common treatment for patients with gastric cancer. Although its benefits have been demonstrated, neoadjuvant chemotherapy is underutilized in gastric cancer management, because of the lack of biomarkers for patient selection and a limited understanding of resistance mechanisms. Here, we performed whole-genome, whole-exome, and RNA sequencing on 84 clinical samples (including matched pre- and posttreatment tumors) from 35 patients whose responses to neoadjuvant chemotherapy were rigorously defined. We observed increased microsatellite instability and mutation burden in nonresponse tumors. Through comparisons of response versus nonresponse tumors and pre- versus posttreatment samples, we found that C10orf71 mutations were associated with treatment resistance, which was supported by drug response data and potentially through inhibition of cell cycle, and that MYC amplification correlated with treatment sensitivity, whereas MDM2 amplification showed the opposite pattern. Neoadjuvant chemotherapy also reshapes tumor-immune signaling and microenvironment. Our study provides a critical basis for developing precision neoadjuvant regimens.

Many primary tumours have low levels of molecular oxygen (hypoxia), and hypoxic tumours respond poorly to therapy. Pan-cancer molecular hallmarks of tumour hypoxia remain poorly understood, with limited comprehension of its associations with specific mutational processes, non-coding driver genes and evolutionary features. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2658 cancers across 38 tumour types, we quantify hypoxia in 1188 tumours spanning 27 cancer types. Elevated hypoxia associates with increased mutational load across cancer types, irrespective of underlying mutational class. The proportion of mutations attributed to several mutational signatures of unknown aetiology directly associates with the level of hypoxia, suggesting underlying mutational processes for these signatures. At the gene level, driver mutations in TP53, MYC and PTEN are enriched in hypoxic tumours, and mutations in PTEN interact with hypoxia to direct tumour evolutionary trajectories. Overall, hypoxia plays a critical role in shaping the genomic and evolutionary landscapes of cancer.