Scattered crypt intestinal epithelial cell apoptosis induces necrotizing enterocolitis via intricate mechanisms.

BACKGROUND & AIMS: Necrotizing enterocolitis (NEC) is a life-threatening disease affecting mostly the ileum of preemies. Intestinal epithelial cell (IEC) apoptosis contributes to NEC pathogenesis. However, how scattered crypt IEC apoptosis leads to NEC with excessive villus epithelial necrosis remains unclear. METHODS: A novel triple-transgenic mouse model, namely, 3xTg-iAPcIEC (inducible apoptosis phenotype in crypt-IEC), was developed to induce IECs-specific overexpression of Fasl transgene using doxycycline (Dox)-inducible tetO-rtTA system and villin-cre technology. The three days old neonatal 3xTg-iAPcIEC mice and their littermate controls were subcutaneously (s.c.) challenged with a single dose of Dox. Intestinal tissues were processed at different time points to examine scattered crypt IEC apoptosis-mediated NEC development. Gene knockout technology, antibody-mediated cell depletion, and antibiotic-facilitated Gram-positive bacteria depletion were used to study mechanisms. RESULTS: Treatment of 3xTg-iAPcIEC mouse pups with Dox induces scattered crypt IEC apoptosis followed by crypt inflammation and excessive villous necrosis resembling NEC. This progression correlated with elevated Ifng, Rip3, CD8+ T cells, and Gram-positive bacteria in the ileum. Mechanistically, IFN-γ and RIP3-activated signals mediate the effect of scattered crypt IEC apoptosis on the induction of intestinal crypt inflammation and villous necrosis. Meanwhile, pathophysiological events of CD8+ T cell infiltration and dysbiosis with Gram-positive bacteria primarily contribute to excessive villous inflammation and necrosis. Notably, blocking any of these events protects against NEC development in 3xTg-iAPcIEC mouse pups, underlining their central roles in NEC pathogenesis. CONCLUSIONS: Scattered crypt IEC apoptosis induces NEC in mouse pups via IFN-γ, RIP3, CD8+ T cells, and Gram-positive bacteria-mediated comprehensive pathophysiological events. Our findings may advance knowledge in the prevention and treatment of NEC.

Genetic substructure and host-specific natural selection trend across vaccine-candidate ORF-2 capsid protein of hepatitis-E virus.

Hepatitis E virus is a primary cause of acute hepatitis worldwide. The present study attempts to assess the genetic variability and evolutionary divergence among HEV genotypes. A vaccine promising capsid-protein coding ORF-2 gene sequences of HEV was evaluated using phylogenetics, model-based population genetic methods and principal component analysis. The analyses unveiled nine distinct clusters as subpopulations for six HEV genotypes. HEV-3 genotype samples stratified into four different subgroups, while HEV-4 stratified into three additional subclusters. Rabbit-infectious HEV-3ra samples constitute a distinct cluster. Pairwise analysis identified marked genetic distinction of HEV-4c and HEV-4i subgenotypes compared to other genotypes. Numerous admixed, inter and intragenotype recombinant strains were detected. The MEME method identified several ORF-2 codon sites under positive selection. Some selection signatures lead to amino acid substitutions within ORF-2, resulting in altered physicochemical features. Moreover, a pattern of host-specific adaptive signatures was identified among HEV genotypes. The analyses conclusively depict that recombination and episodic positive selection events have shaped the observed genetic diversity among different HEV genotypes. The significant genetic diversity and stratification of HEV-3 and HEV-4 genotypes into subgroups, as identified in the current study, are noteworthy and may have implications for the efficacy of anti-HEV vaccines.

A combination of generated hydrogen sulfide and nitric oxide activity has a potentiated protectant effect against cisplatin induced nephrotoxicity.

Aim: Hydrogen sulfide and nitricoxide possess cytoprotective activity and in vivo, they are generated from exogenous sodium hydrosulfide and L-arginine respectively. Cisplatin is a major chemotherapeutic agent used to treat cancer and has a high incidence of nephrotoxicity as a side effect. The study aim was to explore the effects of NaHS and L-arginine or their combination on cisplatin induced nephrotoxicity in rats. Methods: Wistar Kyoto rats were given a single intraperitoneal dose of cisplatin (5 mg/kg) followed either by NaHS (56 µmol/kg, i. p.), L-arginine (1.25 g/L in drinking water) or their combination daily for 28-days. Post-mortem plasma, urine and kidney samples were collected for biochemical assays and histopathological analysis. Results: Cisplatin decreased body weights and increased urinary output, while plasma creatinine and urea levels were elevated, but sodium and potassium concentrations were diminished. The renal function parameters, blood urea nitrogen and creatinine clearance, were raised and decreased respectively. Regarding markers of reactive oxygen species, plasma total superoxide dismutase was reduced, whereas malondiadehyde was augmented.Cisplatin also diminished plasma and urinary H2S as well as plasma NO, while NaHS and L-arginine counteracted this activity on both redox-active molecules. Cisplatin cotreatment with NaHS, and/or L-arginine exhibited a reversal of all other measured parameters. Conclusion: In current study, NaHS and L-arginine as monotherapy protected the rats from cisplatin-induced nephrotoxicity but the combination of both worked more effectively suggesting the augmented anti-inflammatory and antioxidative potential of test treatments when administered together.

Vaccinomics-aided next-generation novel multi-epitope-based vaccine engineering against multidrug resistant Shigella Sonnei: Immunoinformatics and chemoinformatics approaches.

Shigella sonnei is a gram-negative bacterium and is the primary cause of shigellosis in advanced countries. An exceptional rise in the prevalence of the disease has been reported in Asia, the Middle East, and Latin America. To date, no preventive vaccine is available against S. sonnei infections. This pathogen has shown resistances towards both first- and second-line antibiotics. Therefore, an effective broad spectrum vaccine development against shigellosis is indispensable. In the present study, vaccinomics-aided immunoinformatics strategies were pursued to identify potential vaccine candidates from the S. sonnei whole proteome data. Pathogen essential proteins that are non-homologous to human and human gut microbiome proteome set, are feasible candidates for this purpose. Three antigenic outer membrane proteins were prioritized to predict lead epitopes based on reverse vaccinology approach. Multi-epitope-based chimeric vaccines was designed using lead B- and T-cell epitopes combined with suitable linker and adjuvant peptide sequences to enhance immune responses against the designed vaccine. The SS-MEVC construct was prioritized based on multiple physicochemical, immunological properties, and immune-receptors docking scores. Immune simulation analysis predicted strong immunogenic response capability of the designed vaccine construct. The Molecular dynamic simulations analysis ensured stable molecular interactions of lead vaccine construct with the host receptors. In silico restriction and cloning analysis predicted feasible cloning capability of the SS-MEVC construct within the E. coli expression system. The proposed vaccine construct is predicted to be more safe, effective and capable of inducing robust immune responses against S. sonnei infections and may be worthy of examination via in vitro/in vivo assays.

Pancreatic regenerative potential of manuka honey evidenced through pancreatic histology and levels of transcription factors in diabetic rat model.

Background: Diabetes mellitus is a commonly occurring metabolic disorder accompanied by high morbidity and alarming mortality. Besides various available therapies, induction of pancreatic regeneration has emerged as a promising strategy for alleviating the damaging effect of diabetes. Honey, a potent antioxidative and anti-inflammatory agent, has been reported in the literature archive to exhibit favourable results in the regeneration process of several organ systems. Design: The current research work was intended to explore the potential role of manuka honey in pancreatic regeneration in alloxan-induced diabetic rats by accessing the pancreatic histology and levels of relevant transcription factors, including MAFA, PDX-1, INS-1, INS-2, NEUROG3, NKX6-1, and NEUROD. An equal number of rats were allocated to all four experimental groups: normal, negative control, positive control, and treatment group. Diabetes was induced in all groups except normal through a single intraperitoneal dose of alloxan monohydrate. No subsequent treatment was given to the negative control group, while the positive control and treatment groups were supplemented with metformin (150 mg/kg/day) and manuka honey (3 g/kg/day), respectively. Results: Statistical comparison of glucose and insulin levels, oxidative stress indicators, changes in the architecture of pancreatic islets, and expression levels of regeneration-associated transcription factors advocated the potential role of manuka honey in ameliorating the alloxan-induced hyperglycaemia, hyperinsulinemia, oxidative stress, and necrotic changes in islets along with significant upregulation of relevant transcription factors. Conclusion: This suggests to us the auspicious role of antioxidants in honey in pancreatic regeneration and advocates the favourable role of manuka honey in combating diabetes mellitus.

Immunoinformatic-guided novel mRNA vaccine designing to elicit immunogenic responses against the endemic Monkeypox virus.

Monkeypox virus (MPXV) is an orthopoxvirus, causing zoonotic infections in humans with smallpox-like symptoms. The WHO reported MPXV cases in May 2022 and the outbreak caused significant morbidity threats to immunocompromised individuals and children. Currently, no clinically validated therapies are available against MPXV infections. The present study is based on immunoinformatics approaches to design mRNA-based novel vaccine models against MPXV. Three proteins were prioritized based on high antigenicity, low allergenicity, and toxicity values to predict T- and B-cell epitopes. Lead T- and B-cell epitopes were used to design vaccine constructs, linked with epitope-specific linkers and adjuvant to enhance immune responses. Additional sequences, including Kozak sequence, MITD sequence, tPA sequence, Goblin 5', 3' UTRs, and a poly(A) tail were added to design stable and highly immunogenic mRNA vaccine construct. High-quality structures were predicted by molecular modeling and 3D-structural validation of the vaccine construct. Population coverage and epitope-conservancy speculated broader protection of designed vaccine model against multiple MPXV infectious strains. MPXV-V4 was eventually prioritized based on its physicochemical and immunological parameters and docking scores. Molecular dynamics and immune simulations analyses predicted significant structural stability and binding affinity of the top-ranked vaccine model with immune receptors to elicit cellular and humoral immunogenic responses against the MPXV. The pursuance of experimental and clinical follow-up of these prioritized constructs may lay the groundwork to develop safe and effective vaccine against MPXV.Communicated by Ramaswamy H. Sarma.

SEC24D gene as a biomarker in human cancers and its association with CD8+ T cell immune cell infiltration.

OBJECTIVE: The SEC24D (SEC24 Homolog D, COPII Coat Complex Component) gene belongs to the SEC24 subfamily of genes. The protein encoded by this gene, along with its other binding partners, mediates the transport of newly-synthesized proteins from the endoplasmic reticulum to the Golgi apparatus. METHODS: A pan-cancer analysis of this gene, as well as its diagnostic and prognostic implications, are lacking in the medical literature. First, we analyzed SEC24D gene expression, its prognostic effect, promoter methylation level, genetic alteration landscape, pathways, CD8+ T immune cell infiltration, and gene-drug network in various types of cancer through various online databases and bioinformatic tools. Then, we performed the expression and methylation validation analysis of the SEC24D gene on cell lines using RNA sequencing (RNA-seq) and targeted bisulfite sequencing (bisulfite-seq) techniques. RESULTS: Bioinformatic analysis showed that the SEC24D gene was overexpressed in metastasis across Kidney Renal Clear Cell Carcinoma (KIRC), Lung Squamous Cell Carcinoma (LUSC), and Stomach Adenocarcinoma (STAD) patients and was a prognostic risk factor. Then, using RNA sequencing and targeted bisulfite sequencing analysis, it was validated in cell lines that SEC24D was overexpressed and hypomethylated in KIRC patients. Mutational analysis revealed that SEC24D was mutated less frequently in KIRC, LUSC, and STAD patients. It was further observed that CD8+ T cell infiltration levels were increased in SEC24D-overexpressed KIRC, LUSC, and STAD samples. Pathway enrichment analysis of SEC24D-associated genes revealed their participation in two important pathways. Moreover, we suggested a few valuable drugs for treating KIRC, LUSC, and STAD patients with respect to overexpressed SEC24D. CONCLUSION: This is the first pan-cancer study that details the oncogenic roles of SEC24D among different cancers.

Patient Perspectives and Side-Effects Experience on Chemotherapy of Non-Small Cell Lung Cancer: A Qualitative Study.

Purpose: This study aimed to explore patients' experiences of palliative chemotherapy for non-small cell lung cancer (NSCLC), how patients adapt to their new and challenging life after chemotherapy, their beliefs, and their quality of life. Patients and Methods: The study used an exploratory descriptive qualitative approach that was designed to explore the experiences and side effects of NSCLC patients on chemotherapy in Pakistan. The study was designed to obtain a deeper understanding of 22 NSCLC patients' experiences, using a face-to-face approach and interviews were conducted. Patients who have completed chemotherapy agreed to participate in semi-structured interviews. Results: The data were arranged into five themes: hospital facilities and environment, patient's beliefs in alternative treatments, presenting a positive/negative face, life is for living, and health insurance coverage. The major complaints related to bad experiences of chemotherapy-induced side effects, but these patients still managed to complete the full course of their respective chemotherapy. Additionally, the current study revealed the real experience of patients with NSCLC which had been less studied. The patient's experience was summarized into four themes and several subthemes. Conclusion: This study aid healthcare providers when deciding on treatment options that will improve shared decision-making between clinicians and treatment outcomes.

Mannosylated preactivated hyaluronic acid-based nanostructures for bacterial infection treatment.

Salmonella Typhi is an intracellular bacterium causing a variety of enteric diseases, being typhoid fever the most common. Current modalities for treating S. typhi infection are subjected to multi-drug resistance. Herein, a novel macrophage targeting approach was developed via coating bioinspired mannosylated preactivated hyaluronic acid (Man-PTHA) ligands on a self-nanoemulsifying drug delivery system (SNEDDS) loaded with the anti-bacterial drug ciprofloxacin (CIP). The shake flask method was used to determine the drug solubility in the different excipients (oil, surfactants and co-surfactants). Man-PTHA were characterized by physicochemical, in vitro, and in vivo parameters. The mean droplet size was 257 nm, with a PDI of 0.37 and zeta potential of -15 mV. In 72 h, 85 % of the drug was released in a sustained manner, and the entrapment efficiency was 95 %. Outstanding biocompatibility, mucoadhesion, muco-penetration, anti-bacterial action and hemocompatibility were observed. Intra-macrophage survival of S. typhi was minimal (1 %) with maximum nanoparticle uptake, as shown by their higher fluorescence intensity. Serum biochemistry evaluation showed no significant changes or toxicity, and histopathological evaluation confirmed the entero-protective nature of the bioinspired polymers. Overall, results confirm that Man-PTHA SNEDDS can be employed as novel and effective delivery systems for the therapeutic management of S. typhi infection.

A unique investigation of thallium, tellurium, osmium, and other heavy metals in recurrent pregnancy loss: A novel approach.

OBJECTIVE: To study the impact of heavy metals especially tellurium, thallium, and osmium, in recurrent pregnancy loss (RPL) and to study their association with antioxidant status and DNA damage. METHODS: This case-control study included women with RPL (n = 30) and healthy pregnant women as control (n = 30). Following blood collection, serum levels of thallium, tellurium, osmium, lead, mercury, and cadmium were estimated by inductively coupled plasma mass spectrophotometer. RESULTS: Women with RPL exhibited significantly higher levels of heavy metals (P < 0.001) when compared with control women. Intriguingly, increased levels of serum thallium, tellurium, osmium, and lead were negatively correlated with total antioxidant status (P < 0.05). Further, the RPL group demonstrated strong positive correlation between heavy metals (thallium, tellurium, osmium, lead) and DNA damage (P < 0.05). No significant correlation between other heavy metals and markers of cellular damage was noted. CONCLUSION: Enhanced levels of heavy metals in women with RPL and correlation of thallium, tellurium, osmium, and lead with markers of cellular damage reflect the role of heavy metal poisoning, especially thallium, tellurium, and osmium, as potential risk factor in the etiology underlying recurrent miscarriage.

Inhibition of Escherichia coli ATP synthase and cell growth by dietary pomegranate phenolics.

Historically, people have been using pomegranate to alleviate many disease conditions. Pomegranate is known for its antiinflammatory, antioxidant, neuroprotective, anticancer, and antibacterial properties. In the current study, we examined effects of 8 dietary phenolics present in pomegranate (DPPs)-cyanidin-3-glucoside, cyanin chloride, delphinidin-3-glucoside, delphinidin-3,5-diglucoside, pelargonidin-3-glucoside, pelargonin chloride, punicalagin, and punicalin-on Escherichia coli ATP synthase and cell growth. DPPs caused complete or near complete (89%-100%) inhibition of wild-type E. coli ATP synthase and partial (5%-64%) inhibition of mutant enzymes αR283D, αE284R, ßV265Q, and γT273A. Growth inhibition of wild-type, null, and mutant strains in the presence of DPPs were lower than that of isolated wild-type and mutant ATP synthase. On a molar scale, cyanin chloride was the most potent, and pelargonidin-3-glucoside was the least effective inhibitor of wild-type ATP synthase. Partial inhibition of mutant enzymes confirmed that αR283D, αE284R, ßV265Q, and γT273A are essential in the formation of the phytochemical binding site. Our results establish that DPPs are potent inhibitors of wild-type E. coli ATP synthase and that the antimicrobial nature of DPPs can be associated with the binding and inhibition of microbial ATP synthase. Additionally, selective inhibition of microbial ATP synthase by DPPs is a useful method to combat antimicrobial resistance.

Benign tumors in TSC are amenable to treatment by GD3 CAR T cells in mice.

Mutations underlying disease in tuberous sclerosis complex (TSC) give rise to tumors with biallelic mutations in TSC1 or TSC2 and hyperactive mammalian target of rapamycin complex 1 (mTORC1). Benign tumors might exhibit de novo expression of immunogens, targetable by immunotherapy. As tumors may rely on ganglioside D3 (GD3) expression for mTORC1 activation and growth, we compared GD3 expression in tissues from patients with TSC and controls. GD3 was overexpressed in affected tissues from patients with TSC and also in aging Tsc2+/- mice. As GD3 overexpression was not accompanied by marked natural immune responses to the target molecule, we performed preclinical studies with GD3 chimeric antigen receptor (CAR) T cells. Polyfunctional CAR T cells were cytotoxic toward GD3-overexpressing targets. In mice challenged with Tsc2-/- tumor cells, CAR T cells substantially and durably reduced the tumor burden, correlating with increased T cell infiltration. We also treated aged Tsc2+/- heterozygous (>60 weeks) mice that carry spontaneous Tsc2-/- tumors with GD3 CAR or untransduced T cells and evaluated them at endpoint. Following CAR T cell treatment, the majority of mice were tumor free while all control animals carried tumors. The outcomes demonstrate a strong treatment effect and suggest that targeting GD3 can be successful in TSC.

A stability perspective of bioinspired unmanned aerial vehicles performing optimal dynamic soaring.

The phenomenon of dynamic soaring, as exhibited by soaring birds, has long been a biological inspiration for aerospace and control engineers. If this fascinating phenomenon, which allows soaring birds to perform almost unpowered flight using wind shear, can be mimicked by unmanned aerial vehicles (UAVs), then there is substantial potential for technological and economic enhancement of UAV performance. Although there has been a considerable amount of research covering the modeling, optimization, control and simulation aspects of different UAVs performing dynamic soaring, there is little to no conclusive work analyzing the stability of such UAVs in soaring orbits. In this paper we present a comprehensive framework for determining the stability of soaring UAVs utilizing both linear (Floquet-based) and nonlinear (contraction theory-based) techniques. Floquet stability analysis was inconclusive, which led to the use of a nonlinear contraction formulation to reach a conclusive stability assessment for an actual nonlinear fixed-wing UAV performing dynamic soaring. Furthermore, parametric variation along with numerical simulations were conducted to ascertain the response of the actual nonlinear system when perturbed from the nominal motion studied in this paper. The analysis and simulations revealed that the system possesses instability as the UAV motion diverges from its nominal trajectory and follows an undesirable path. From this result we conclude, for the first time in the literature as far as we are aware, that UAVs performing dynamic soaring in an optimal way to reduce wind shear requirements are inherently unstable. The results of this work suggest that mimicking of dynamic soaring by UAVs will require careful investigation of tracking and regulatory controls that need to be implemented.

Antibiotics Drive Microbial Imbalance and Vitiligo Development in Mice.

Vitiligo is impacted by environmental triggers. We studied the contribution of the microbiome in FH mice, in which depigmentation is mediated by tyrosinase-reactive T cells. The mice received oral antibiotics and were monitored for depigmentation. The microbiome was studied in fecal and skin samples using 16S rRNA analysis. The resulting T-cell distributions were evaluated. In untreated mice, pigment loss did not expand to the pelage, whereas mice in the ampicillin group were approximately 1/3 depigmented at 30 weeks. In contrast to models of autoimmunity that are less dependent on IFN-γ, ampicillin but not neomycin treatment correlated with accelerated disease and reduced bacteria in the fecal pellets. Modified cytokine patterns in the tissue and serum suggest a response that transcends the gut. Ampicillin-induced depigmentation was accompanied by gut but not skin dysbiosis, and reduced T cell numbers in both sites. Neomycin induced a redistribution of gut T cells and an accumulation of skin regulatory T cells. This treatment spurred a Bacteroides-dominated population of fecal bacteria. Reduced diversity is prominent particularly after ampicillin treatment, when the gut is dominated by Pseudomonas species. In line with current concepts relating the microbiome and the immune system, we predict that dietary measures might promote skin health and delay vitiligo onset.

Fetal exposure to the maternal microbiota in humans and mice.

Previous studies have demonstrated the presence of microbial DNA in the fetal environment. However, it remains unclear whether this DNA represents viable bacteria and how it relates to the maternal microbiota across body sites. We studied the microbiota of human and mouse dyads to understand these relationships, localize bacteria in the fetus, and demonstrate bacterial viability. In human preterm and full-term mother-infant dyads at the time of cesarean delivery, the oral cavity and meconium of newborn infants born as early as 24 weeks of gestation contained a microbiota that was predicted to originate from in utero sources, including the placenta. Using operative deliveries of pregnant mice under highly controlled, sterile conditions in the laboratory, composition, visualization, and viability of bacteria in the in utero compartment and fetal intestine were demonstrated by 16S rRNA gene sequencing, fluorescence in situ hybridization, and bacterial culture. The composition and predicted source of the fetal gut microbiota shifted between mid- and late gestation. Cultivatable bacteria in the fetal intestine were found during mid-gestation but not late gestation. Our results demonstrate a dynamic, viable mammalian fetal microbiota during in utero development.

miR-144-mediated Inhibition of ROCK1 Protects against LPS-induced Lung Endothelial Hyperpermeability.

Dysfunctional endothelial cell (EC) barrier and increased lung vascular permeability is a cardinal feature of acute lung injury and sepsis that may result in a pathophysiological condition characterized by alveolar flooding, pulmonary edema, and subsequent hypoxemia. In lung ECs, activation of Rho-associated kinase-1 (ROCK1) phosphorylates myosin light chain (MLC)-associated phosphatase at its inhibitory site, which favors phosphorylation of MLC, stress fiber formation, and hyperpermeability during acute lung injury. The role of microRNA-144 (miR-144) has been well investigated in many human diseases, including cardiac ischemia/reperfusion-induced injury, lung cancer, and lung viral infection; however, its role in pulmonary EC barrier regulation remains obscure. Here, we investigated the miR-144-mediated mechanism in the protection of endothelial barrier function in an LPS-induced lung injury model. By using transendothelial electrical resistance and transwell permeability assay to examine in vitro permeability and immunofluorescence microscopy to determine barrier integrity, we showed that ectopic expression of miR-144 effectively blocked lung EC barrier disruption and hyperpermeability in response to proinflammatory agents. Furthermore, using a gain-and-loss-of-function strategy, overexpression of miR-144 significantly decreased ROCK1 expression. Concomitantly, miR-144 inhibits ROCK1-mediated phosphorylation of MLC phosphataseThr853 and thus phosphorylation of MLCThr18/Ser19 to counteract stress fiber formation in LPS-activated EC. Finally, in LPS-challenged mice, intranasal delivery of miR-144 mimic via liposomes attenuated endotoxemia-induced increases in lung wet/dry ratio, vascular permeability, and inflammation. In conclusion, these data suggest that miR-144-attenuated activation of inflammatory ROCK1/MLC pathway in vascular ECs is a promising therapeutic strategy to counter inflammatory lung injury.

An SOI CMOS-Based Multi-Sensor MEMS Chip for Fluidic Applications.

An SOI CMOS multi-sensor MEMS chip, which can simultaneously measure temperature, pressure and flow rate, has been reported. The multi-sensor chip has been designed keeping in view the requirements of researchers interested in experimental fluid dynamics. The chip contains ten thermodiodes (temperature sensors), a piezoresistive-type pressure sensor and nine hot film-based flow rate sensors fabricated within the oxide layer of the SOI wafers. The silicon dioxide layers with embedded sensors are relieved from the substrate as membranes with the help of a single DRIE step after chip fabrication from a commercial CMOS foundry. Very dense sensor packing per unit area of the chip has been enabled by using technologies/processes like SOI, CMOS and DRIE. Independent apparatuses were used for the characterization of each sensor. With a drive current of 10 µA-0.1 µA, the thermodiodes exhibited sensitivities of 1.41 mV/°C-1.79 mV/°C in the range 20-300 °C. The sensitivity of the pressure sensor was 0.0686 mV/(Vexcit kPa) with a non-linearity of 0.25% between 0 and 69 kPa above ambient pressure. Packaged in a micro-channel, the flow rate sensor has a linearized sensitivity of 17.3 mV/(L/min)-0.1 in the tested range of 0-4.7 L/min. The multi-sensor chip can be used for simultaneous measurement of fluid pressure, temperature and flow rate in fluidic experiments and aerospace/automotive/biomedical/process industries.