Molecular Imprinting-Based SERS Detection Strategy for the Large-Size Protein Quantitation and Curbing Non-Specific Recognition.

Molecular imprinting-based surface-enhanced Raman scattering (MI-SERS) sensors have shown remarkable potential from an academic standpoint. However, their practical applications, especially in the detection of large-size protein (≥10 nm), face challenges due to the lack of versatile sensing strategies and nonspecific fouling of matrix species. Herein, we propose a Raman reporter inspector mechanism (RRIM) implemented on a protein-imprinted polydopamine (PDA) layer coated on the SERS active substrate. In the RRIM, after large-size protein recognition, the permeability of the PDA imprinted cavities undergoes changes that are scrutinized by Raman reporter molecules. Target proteins can specifically bind and fully occupy the imprinted cavities, whereas matrix species cannot. Then, Raman reporter molecules with suitable size are introduced to serve as both inspectors of the recognition status and inducers of the SERS signal, which can only penetrate through the vacant and nonspecifically filled cavities. Consequently, changes in the SERS signal exclusively originate from the specific binding of target proteins, while the nonspecific recognition of matrix species is curbed. The RRIM enables reproducible quantitation of the large-size cyanobacteria-specific protein model (≥10 nm), phycocyanin, at the level down to 2.6 × 10-3 µg L-1. Finally, the practical applicability of the RRIM is confirmed by accurately analyzing crude urban waterway samples over 21 min without any pretreatment.

Respiratory failure and rhabdomyolysis caused by severe hypokalemia in a young female with hypertension: a rare critical condition in primary aldosteronism.

BACKGROUND: The two classic manifestations of primary aldosteronism are hypertension and hypokalemia. However, acute respiratory failure due to hypokalemia in primary hyperaldosteronism is rare. CASE PRESENTATION: The patient was a 27-year-old female who presented with drowsiness and weakness in all extremities. She had been diagnosed with hypertension three years prior, with irregular follow-up, and had a history of preeclampsia one year later. She exhibited high blood pressure and severe hypokalemia (2 mEq/L), leading to respiratory depression and impending respiratory arrest. Consequently, the patient was intubated and transferred to the intensive care unit (ICU). She also developed rhabdomyolysis. Blood pressure tests, including hormonal tests (aldosterone: 13.2 ng/dL, plasma renin activity: 0.32 ng/mL/h), were conducted. Due to the high aldosterone-renin ratio, an abdominopelvic computed tomography (CT) scan was performed. The CT scan revealed a 14 × 12 mm round mass with a washout value above 60%, consistent with an adrenal adenoma, leading to a diagnosis of primary aldosteronism. The patient was discharged after stabilization, and one and a half months after ICU admission, a laparoscopic left adrenalectomy was successfully performed without post-operative complications. Histopathology showed encapsulated hypertrophy of the adrenal cortex with a predominance of large clear cells, confirming the diagnosis of adrenal adenoma. At the most recent follow-up, the patient had normal potassium levels, was normotensive without any medications, and exhibited no alarming signs or symptoms. CONCLUSION: Respiratory depression to the extent of impending respiratory failure and rhabdomyolysis as a result of hypokalemia in primary aldosteronism are extremely rare. In this patient, who developed respiratory depression due to resistant hypokalemia, timely investigation of secondary causes and diagnosis of adrenal adenoma were crucial. The surgery provided definitive treatment for the patient's blood pressure and prevented the recurrence of life-threatening complications.

Severity of the Omicron SARS-CoV-2 variant compared with the previous lineages: A systematic review.

The Omicron variant was first detected in October 2021, which evolved from the original SARS-CoV-2 strain and was found to possess many mutations. Immune evasion was one of the notable consequences of these mutations. Despite Omicron exhibiting increased transmissibility, the rates of hospitalizations and deaths among patients infected with this variant were substantially lower when compared to other strains. However, concluding that the Omicron variant is less severe than other variants of SARS-CoV-2 requires consideration of multiple factors, including the vaccination status of infected patients as well as any previous infections with other variants. This review compiled data about any reported indicators of severity in Omicron-infected patients, including studies comparing Omicron with other variants while adjusting for confounders. A comprehensive search was conducted using different databases to target any studies about Omicron. In total, 62 studies met our inclusion criteria and were included in this study. Many studies reported a significantly reduced risk of hospitalization, ICU admission, need for oxygenation/ventilation, and death in Omicron-infected patients compared to patients infected with other variants, such as Delta. Some studies, however, reported comparable severity in Omicron infected patients as to other variants emphasizing a substantial risk for severe illness. Furthermore, the COVID-19 vaccines were less effective against Omicron relative to previous lineages, except after receiving the booster dose. One study recommended vaccination during pregnancy, which may help prevent future cases of severe SARS-CoV-2 pneumonia in neonates and young infants due to the transfer of humoral response from the mother.

Role of previous infection with SARS-CoV-2 in protecting against omicron reinfections and severe complications of COVID-19 compared to pre-omicron variants: a systematic review.

BACKGROUND: The SARS-CoV-2 virus elicited a major public concern worldwide since December 2019 due to the high number of infections and deaths caused by COVID-19. The Omicron variant was detected in October 2021 which evolved from the wild-type SARS-CoV-2 and was found to possess many mutations. Omicron exhibited high transmissibility and immune evasion as well as reduced severity when compared to the earlier variants. Although vaccinated individuals were largely protected against infections in previous waves, the high prevalence of both reinfections and breakthrough infections with Omicron was observed. The aim of this review is to understand the effectiveness of previous infection on subsequent reinfection, given its significance in driving public health policy, including vaccination prioritization and lockdown requirements. METHODS: A comprehensive literature search was conducted using several databases to target studies reporting data related to the effectiveness of the previous infection with SARS-CoV-2 in protecting against the Omicron variant. Screening of the studies, quality assessment and data extraction were conducted by two reviewers for each study. RESULTS: Only 27 studies met our inclusion criteria. It was observed that previous infection was less effective in preventing reinfections with the Omicron variant compared to the Delta variant irrespective of vaccination status. Furthermore, being fully vaccinated with a booster dose provided additional protection from the Omicron variant. Additionally, most infections caused by Omicron were asymptomatic or mild and rarely resulted in hospitalizations or death in comparison to the Delta wave. CONCLUSION: A majority of the studies reached a consensus that although previous infection provides some degree of immunity against Omicron reinfection, it is much lower in comparison to Delta. Full vaccination with two doses was more protective against Delta than Omicron. Receiving a booster dose provided additional protection against Omicron. It is therefore clear that neither vaccination nor previous infection alone provide optimal protection; hybrid immunity has shown the best results in terms of protecting against either Omicron or Delta variants. However, additional research is needed to quantify how long immunity from vaccination versus previous infection lasts and whether individuals will benefit from variant-specific vaccinations to enhance protection from infection.

Synthesis and evaluation of ginsenosides imprinted polymer-based chromatographic stationary phase.

The molecular imprinting technique has aroused great interest in preparing novel stationary phases, and the resulting materials named molecularly imprinted polymers coated silica packing materials exhibit good performance in separating diverse analytes based on their good characteristics (including high selectivity, simple synthesis, and good chemical stability). To date, mono-template is commonly used in synthesizing molecularly imprinted polymers-based stationary phases. The resulting materials always own the disadvantages of low column efficiency and restricted analytes, and the price of ginsenosides with high purity was very high. In this study, to overcome the weaknesses of molecularly imprinted polymers-based stationary phases mentioned above, the multi-templates (total saponins of folium ginseng) strategy was used to prepare ginsenosides imprinted polymer-based stationary phase. The resulting ginsenosides imprinted polymer-coated silica stationary phase has a good spherical shape and suitable pore structures. Additionally, the total saponins of folium ginseng were cheaper than other kinds of ginsenosides. Moreover, the ginsenosides imprinted polymer-coated silica stationary phase-packed column performed well in the separation of ginsenosides, nucleosides, and sulfonamides. The ginsenosides imprinted polymer-coated silica stationary phase possesses good reproducibility, repeatability, and stability for seven days. Therefore, a multi-templates strategy for synthesizing the ginsenosides imprinted polymer-coated silica stationary phase is considered in the future.

Technical Challenges of Molecular-Imprinting-Based Optical Sensors for Environmental Pollutants.

Combating environmental pollution constantly requires new affinity tools to selectively recognize and sensitively detect them. Molecularly imprinted polymers (MIPs) are plastic antibodies that have exhibited great potential as recognition units in optical sensing platforms to monitor wide varieties of environmental pollutants, including ionic species, organic compounds, gases, and even manufactured nanoparticles. The construction, sensing strategies, and applications of molecular-imprinting-based optical sensors (MI-OSs) have been discussed in recent reviews, thus we deliberately set them aside. This Perspective elaborates on unanswered questions and main approaches being taken to address the challenges of MI-OS technologies, which have been less considered until now. Specifically, we highlight obscure technical aspects of MI-OS fabrication and validation that impact their practical applications and importantly offer conceivable solutions to related problems to bridge the research gap.

The effect of microbiome-modulating probiotics, prebiotics and synbiotics on glucose homeostasis in type 2 diabetes: A systematic review, meta-analysis, and meta-regression of clinical trials.

AIM/HYPOTHESIS: The globally escalating diabetes epidemic is responsible for significant morbidity and mortality. Microbiome-modulating nutraceuticals have been investigated for their potential to restore metabolic and floral homeostasis in type 2 diabetic patients METHODS: A systematic review, meta-analyses and meta-regressions were conducted to investigate the effect of probiotics, prebiotics, and synbiotics on various biomarkers of glucose homeostasis based on a multi-database search of clinical trials published through April 10, 2022. Data was pooled using random effects meta-analyses and reported as mean differences with 95% confidence intervals (CIs), followed by univariate linear model meta-regression. RESULTS: Data from 68 trial comparisons across 58 studies (n = 3835) revealed that, compared to placebo/control group, administration of pro/pre/synbiotics was associated with statistically significant changes in fasting plasma glucose (-12.41 mg/dl [95% CI: -15.94; -8.88], p 0.0001), glycated hemoglobin (-0.38% [95% CI: -0.47; -0.30], p 0.0001), fasting insulin (-1.49 µU/mL [95% CI: -2.12; -0.86], p 0.0001), HOMA-IR (-0.69 [95% CI: -1.16; -0.23], p = 0.0031) and QUICKI (0.0148 [95% CI: 0.0052; 0.0244], p = 0.0025), but not C-peptide (-0.0144 ng/mL [95% CI: -0.2564; -0.2275], p = 0.9069). Age, baseline BMI, baseline biomarker value, pro/prebiotic dosage, trial duration, nutraceutical type, and recruitment region significantly affected the potential of pro/pre/synbiotics use as personalized diabetes adjunct therapy. Lastly, we discuss unexplained observations and directives for future trials, with the aim of maximizing our understanding of how microbiome-modulating nutraceuticals can treat various metabolic diseases CONCLUSIONS: Pro/pre/synbiotic supplementation improved glucose homeostasis in diabetic patients. Our results support their potential use as adjunct therapy for improving glycemia and insulinemia alongside pharmacological therapeutics.

A ZnFe2O4-catalyzed segment imprinted polymer on a three-dimensional origami paper-based microfluidic chip for the detection of microcystin.

Microcystin has been causing serious environmental pollution; however, the recognition of such compounds is still challenging because of low abundance and coexisting interfering species. In this contribution, we develop a novel microfluidic paper-based colorimetric sensor by exploiting molecular imprinting technology and Fenton reaction for on-site microcystin-RR determination in complex water samples using a smartphone.

Brown adipose tissue transplantation as a novel alternative to obesity treatment: a systematic review.

BACKGROUND: Obesity, a global challenge, is a complex disorder linked to various diseases. Different kinds of treatments are currently used to treat or control this pandemic. Despite their positive effects on controlling obesity, they still have limitations and side effects including digestive problems, difficulties of daily infusion of some drugs, surgical complications, and weight regain. All these issues cause these conventional methods not to have desirable efficacy. In this regard, brown adipose tissue (BAT) transplantation as a new investigational treatment is proposed, which has beneficial effects with no documented side effect in studies up to now. METHODS: This systematic review protocol was registered in the International Prospective Register of Systematic Reviews (Registration Number: CRD42018110045). The systematical search was conducted on Web of Science, Scopus, PubMed, Embase, and ProQuest databases. The quality assessments in the included studies and data gathering were conducted independently by two authors. The main variables were anthropometric indices including body weight, levels of leptin, IGF-1, glucagon, adiponectin, fasting blood glucose, and UCP-1. RESULTS: Following the search in mentioned databases, ten articles were entered into this systematic review. In most studies, weight gain and white adipocyte size were reduced in the BAT transplant group. It seems that the transplantation leads to the regeneration of healthy adipose tissue by activating the endogenous BAT. CONCLUSIONS: Since BAT transplantation is one of the possible future treatments of obesity, many studies are conducted to evaluate the outcomes and related procedures precisely, so it can finally step into clinical application.

Construction of molecularly imprinted nanoparticles by employing ultrasound waves for selective determination of doxepin from human plasma samples: Modeling and optimization.

In this work, molecularly imprinted nanoparticles (MINPs) were applied as selective adsorbent for ultrasound-assisted micro-solid-phase extraction (UAMSPE) of doxepin (DP) from human plasma samples, which was then cleaned up, pre-concentrated and subjected to HPLC. The MINPs were synthesized based on a non-covalent approach by precipitation polymerization utilizing methacrylic acid and styrene as functional monomers, DP as template, ethylene glycol dimethacrylate as cross-linker and 2,2-azobisisobutyronitrile (AIBN) as initiator. The obtained MINPs were characterized by Fourier transform-infrared and field emission scanning electron microscopy. Factors influencing the efficiency of UAMSPE such as sonication time, volume of eluent solvent and amount of sorbent were investigated using a central composite design and the optimal points were identified as 4 min of sonication time, 380 µL of eluent solvent and 30 mg of sorbent. Under optimized conditions, the proposed method has linear responses in the range of 0.2-2000 ng mL-1 , with a satisfactory limit of detection of 0.04 ng mL-1 and limit of quantification of 0.11 ng mL-1 .

Preparation of hollow porous molecularly imprinted and aluminum(III) doped silica nanospheres for extraction of the drugs valsartan and losartan prior to their quantitation by HPLC.

Water compatible hollow porous molecularly imprinted nanospheres (HP-MINs) have been prepared for specific recognition and extraction of the blood pressure regulating drugs valsartan (VAL) and losartan (LOS). All synthetic steps were performed in aqueous medium and without consumption of organic solvents. The morphology and functionality of the materials were characterized by FT-IR, FE-SEM, and TEM techniques. The adsorption and selectivity experiments demonstrate that the HP-MINs possess a high binding capacity, fast kinetics, excellent water dispersibility and remarkable selectivity for VAL and LOS. The HP-MINs were utilized for dispersive solid phase extraction of VAL and LOS prior to their determination by HPLC-UV. Main variables and their interactions on extraction yield were optimized by multivariate analysis with least amount of experiments. Under optimized conditions, the method has a linear response in the 5-2000 µg L-1 concentration range of both VAL and LOS. The limits of detection are 1.5 µg L-1 for VAL and 1.4 µg L-1 for LOS. Graphical abstract Schematic representation of dispersive solid phase extraction (d-SPE) of valsartan (VAL) and losartan (LOS) from urine sample by hollow porous molecularly imprinted nanospheres (HP-MINs).

Metal-organic framework-based SERS chips enable in situ and sensitive detection of dissolved hydrogen sulfide in natural water: Towards a bring-back-chip mode for field analysis.

Hydrogen sulfide (H2S) in natural water plays an important role in carbon and sulfur cycles in biosphere. Current detection protocol is complicated, which need to "bring back water" to lab followed by gas chromatograph analysis. In situ, field detection is still challenging. Herein, a portable, sensitive surface enhanced Raman scattering (SERS) chip was proposed for in situ H2S sampling and SERS signal stabilizing, enabling a "bring back chip" manner for lab analysis. The SERS chip was composed of single core-shell gold nanorod-ZIF-8 framework (Au NR@ZIF-8) nanoparticle. Relying on headspace adsorption, evaporated H2S was enriched in the ZIF-8 shell and then reacted with Au NR, resulting in the weakening of the Au-Br bond Raman peak (175 cm-1) and the appearance of the Au-S bond Raman peak (273 cm-1). The SERS signal reached equilibrium in 10 min. The detection range of H2S was 0.1-2000 µg/L and limit of detection was 0.098 µg/L. SERS signal was not interfered by normal volatile gases. Moreover, SERS signal of a reacted chip was stable at an ambient condition, allowing for in situ sampling and bring-back detection. The applicability of the chip was verified by dynamic H2S monitoring during artificial black-odor water evolution, and in-field quantitative analysis of H2S content in river water and sediment. Finally, the chip was sealed in a waterproof breathable membrane device, which realized the detection of vertical profiles of H2S in the river. This work provided a promising tool for field analysis of H2S in natural environments.

Molecular imprinting-based indirect fluorescence detection strategy implemented on paper chip for non-fluorescent microcystin.

Fluorescence analysis is a fast and sensitive method, and has great potential application in trace detection of environmental toxins. However, many important environmental toxins are non-fluorescent substances, and it is still a challenge to construct a fluorescence detection method for non-fluorescent substances. Here, by means of charge transfer effect and smart molecular imprinting technology, we report a sensitive indirect fluorescent sensing mechanism (IFSM) and microcystin (MC-RR) is selected as a model target. A molecular imprinted thin film is immobilized on the surface of zinc ferrite nanoparticles (ZnFe2O4 NPs) by using arginine, a dummy fragment of MC-RR. By implementation of IFSM on the paper-based microfluidic chip, a versatile platform for the quantitative assay of MC-RR is developed at trace level (the limit of detection of 0.43 µg/L and time of 20 min) in real water samples without any pretreatment. Importantly, the proposed IFSM can be easily modified and extended for the wide variety of species which lack direct interaction with the fluorescent substrate. This work offers the potential possibility to meet the requirements for the on-site analysis and may explore potential applications of molecularly imprinted fluorescent sensors.

Risk of secondary tumours in patients with non-metastatic and metastatic human retinoblastoma.

BACKGROUND: Retinoblastoma is an intraocular cancer in children and infants. Despite all the available treatment options and high survival rates in children with retinoblastoma, exposure to secondary tumours in adulthood is one of the concerns that physicians face. In many cases, dysfunction of the RB1 gene is the main cause of secondary tumours due to retinoblastoma. Therefore, the aim of this study was to evaluate the incidence of other secondary tumours in children with retinoblastoma. METHODS: In this regard, we performed continuous and integrated bioinformatics analyses to find genes, protein products, and signal pathways involved in other cancers. RESULTS: 1170 high-expression genes and 960 low-expression genes between non-invasive and invasive retinoblastoma were isolated. After examining the signal pathways, we observed bladder cancer and small cell lung cancer in the overexpressed genes. We also observed 5 cancers of endometriosis, prostate, non-small cell lung cancer, glioblastoma and renal cell carcinoma in low-expression genes. Based on the P-value index, non-small cell lung cancer, prostate and bladder cancers had the highest risk, and endometriosis cancer showed a lower probability of developing a secondary tumour in patients with retinoblastoma. In addition, the network between proteins also showed us that TP53, CDK2, SRC, MAPK1 proteins with high expression and JUN, HSP90AA1, and UBC proteins with low-expression play a significant role in candidate cancers. CONCLUSION: Lastly, we used continuous bioinformatics analysis to show that seven cancers are strongly linked to retinoblastoma cancer. Of course, more research is needed to find the best way to care for children who have been treated for retinoblastoma.

Can probiotic, prebiotic, and synbiotic supplementation modulate the gut-liver axis in type 2 diabetes? A narrative and systematic review of clinical trials.

Background: Type 2 diabetes, one of the most common noncommunicable diseases, is a metabolic disorder that results in failed homeostatic control in several body systems, including hepatic function. Due to the gut microbiome's potential role in diabetes' pathogenesis, prebiotics, probiotics, and synbiotics have been proposed as complimentary therapeutic approaches aimed at microbiota readjustment. Methods: A systematic review was conducted on PubMed, Scopus, Web of Science, Embase, and the Cochrane Library examining the effect of probiotics, prebiotics, and synbiotics on hepatic biomarkers in patients with diabetes. Results: From 9,502 search hits, 10 studies met the inclusion criteria and were included in this review. A total of 816 participants (460 intervention and 356 control) were investigated for the effects of nine different hepatic biomarker measurements including aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total protein, bilirubin, liver steatosis, liver stiffness, fatty liver index, and gamma-glutamyl transferase levels. Of the 13 intervention groups analyzed from the 10 studies, 3 were prebiotic interventions, 3 were single species probiotic interventions, 3 were multi-species probiotic interventions, and 4 were synbiotic interventions. Nutraceuticals used in these trials included six genera of bacteria (Lactobacillus, Bifidobacterium, Streptococcus, Acetobacter, Lactococcus, and Propionibacterium), five different prebiotic formulations (inulin, inulin and beta carotene, chicory inulin enriched with oligofructose, galacto-oligosaccharides syrup, and powdered cinnamon), or a combination of these to form multi-species probiotics or synbiotics. Conclusion: Although some studies showed insignificant changes in hepatic biomarkers, generally the results yielded a decrease in liver damage due to reduced oxidative stress, pro-inflammatory cytokines, gut dysbiosis, and insulin resistance which led to improvements in hepatic biomarker levels.

Chiral molecular imprinting-based SERS detection strategy for absolute enantiomeric discrimination.

Chiral discrimination is critical in environmental and life sciences. However, an ideal chiral discrimination strategy has not yet been developed because of the inevitable nonspecific binding entity of wrong enantiomers or insufficient intrinsic optical activities of chiral molecules. Here, we propose an "inspector" recognition mechanism (IRM), which is implemented on a chiral imprinted polydopamine (PDA) layer coated on surface-enhanced Raman scattering (SERS) tag layer. The IRM works based on the permeability change of the imprinted PDA after the chiral recognition and scrutiny of the permeability by an inspector molecule. Good enantiomer can specifically recognize and fully fill the chiral imprinted cavities, whereas the wrong cannot. Then a linear shape aminothiol molecule, as an inspector of the recognition status is introduced, which can only percolate through the vacant and nonspecifically occupied cavities, inducing the SERS signal to decrease. Accordingly, chirality information exclusively stems from good enantiomer specific binding, while nonspecific recognition of wrong enantiomer is curbed. The IRM benefits from sensitivity and versatility, enabling absolute discrimination of a wide variety of chiral molecules regardless of size, functional groups, polarities, optical activities, Raman scattering, and the number of chiral centers.

Greenificated Molecularly Imprinted Materials for Advanced Applications.

Molecular imprinting technology (MIT) produces artificial binding sites with precise complementarity to substrates and thereby is capable of exquisite molecular recognition. Over five decades of evolution, it is predicted that the resulting host imprinted materials will overtake natural receptors for research and application purposes, but in practice, this has not yet been realized due to the unsustainability of their life cycles (i.e., precursors, creation, use, recycling, and end-of-life). To address this issue, greenificated molecularly imprinted polymers (GMIPs) are a new class of plastic antibodies that have approached sustainability by following one or more of the greenification principles, while also demonstrating more far-reaching applications compared to their natural counterparts. In this review, the most recent developments in the delicate design and advanced application of GMIPs in six fast-growing and emerging fields are surveyed, namely biomedicine/therapy, catalysis, energy harvesting/storage, nanoparticle detection, gas sensing/adsorption, and environmental remediation. In addition, their distinct features are highlighted, and the optimal means to utilize these features for attaining incredibly far-reaching applications are discussed. Importantly, the obscure technical challenges of the greenificated MIT are revealed, and conceivable solutions are offered. Lastly, several perspectives on future research directions are proposed.

The Promising Role of Microbiome Therapy on Biomarkers of Inflammation and Oxidative Stress in Type 2 Diabetes: A Systematic and Narrative Review.

Background: One in 10 adults suffer from type 2 diabetes (T2D). The role of the gut microbiome, its homeostasis, and dysbiosis has been investigated with success in the pathogenesis as well as treatment of T2D. There is an increasing volume of literature reporting interventions of pro-, pre-, and synbiotics on T2D patients. Methods: Studies investigating the effect of pro-, pre-, and synbiotics on biomarkers of inflammation and oxidative stress in T2D populations were extracted from databases such as PubMed, Scopus, Web of Science, Embase, and Cochrane from inception to January 2022. Results: From an initial screening of 5,984 hits, 47 clinical studies were included. Both statistically significant and non-significant results have been compiled, analyzed, and discussed. We have found various promising pro-, pre-, and synbiotic formulations. Of these, multistrain/multispecies probiotics are found to be more effective than monostrain interventions. Additionally, our findings show resistant dextrin to be the most promising prebiotic, followed closely by inulin and oligosaccharides. Finally, we report that synbiotics have shown excellent effect on markers of oxidative stress and antioxidant enzymes. We further discuss the role of metabolites in the resulting effects in biomarkers and ultimately pathogenesis of T2D, bring attention toward the ability of such nutraceuticals to have significant role in COVID-19 therapy, and finally discuss few ongoing clinical trials and prospects. Conclusion: Current literature of pro-, pre- and synbiotic administration for T2D therapy is promising and shows many significant results with respect to most markers of inflammation and oxidative stress.

Molecular Imprinting: Green Perspectives and Strategies.

Advances in revolutionary technologies pose new challenges for human life; in response to them, global responsibility is pushing modern technologies toward greener pathways. Molecular imprinting technology (MIT) is a multidisciplinary mimic technology simulating the specific binding principle of enzymes to substrates or antigens to antibodies; along with its rapid progress and wide applications, MIT faces the challenge of complying with green sustainable development requirements. With the identification of environmental risks associated with unsustainable MIT, a new aspect of MIT, termed green MIT, has emerged and developed. However, so far, no clear definition has been provided to appraise green MIT. Herein, the implementation process of green chemistry in MIT is demonstrated and a mnemonic device in the form of an acronym, GREENIFICATION, is proposed to present the green MIT principles. The entire greenificated imprinting process is surveyed, including element choice, polymerization implementation, energy input, imprinting strategies, waste treatment, and recovery, as well as the impacts of these processes on operator health and the environment. Moreover, assistance of upgraded instrumentation in deploying greener goals is considered. Finally, future perspectives are presented to provide a more complete picture of the greenificated MIT road map and to pave the way for further development.

Label-free SERS detection of Raman-Inactive protein biomarkers by Raman reporter indicator: Toward ultrasensitivity and universality.

It is still challenging to sensitively detect protein biomarkers via surface-enhanced Raman scattering (SERS) technique owing to their low Raman activity. SERS tag-based immunoassay is usually applied; however, it is laborious and needs specific antibodies. Herein, an ultrasensitive and universal "Raman indicator" sensing strategy is proposed for protein biomarkers, with the aid of a glass capillary-based molecularly imprinted SERS sensor. The sensor consists of an inner SERS substrate layer for signal enhancement and an outer mussel-inspired polydopamine imprinted layer as a recognition element. Imprinted cavities have two missions: first, selectively capturing the target protein, and second, the only passageway of Raman indicator to access SERS substrate. Specific protein recognition means filling imprinted cavities and blocking Raman indicator flow. Thus, the quantity of captured protein can be reflected by the signal decrease of ultra-Raman active indicator molecule. The capillary sensor exhibited specific and reproducible detection at the level down to 4.1 × 10-3 µg L-1, for trypsin enzyme in as-received biological samples without sample preparation. The generality of the mechanism is confirmed by using three different protein models. This platform provides a facile, fast and general route for sensitive SERS detection of Raman inactive biomacromolecules, which offers great promising utility for in situ and fast point-of-care practical bioassay.