Search

Background: Patients with primary hyperparathyroidism (PHPT) are at risk for severe hypocalcemia (SH) following parathyroidectomy (PTX), but limited data exist on the predictors of SH. We aimed to identify risk factors for early postoperative SH after PTX in patients with PHPT and to evaluate the predictive value of clinical parameters. Methods: A retrospective review of patients with PHPT who underwent PTX between January 2010 and December 2022 was performed. A total of 46 patients were included in the study, with 15 (32.6%) experiencing postoperative SH, 19 (41.3%) having calculi in the ureter or kidney, and 37 (80.4%) having osteoporosis. Patients were divided into SH and non-SH groups based on postoperative serum calcium levels. Preoperative biochemical indicators, bone turnover markers, and renal function parameters were analyzed and correlated with postoperative SH. Results: Statistically significant (P < 0.05) differences were found in preoperative serum calcium (serum Ca), intact parathyroid hormone, serum phosphorus (serum P), serum Ca/P, percentage decrease of serum Ca, total procollagen type 1 intact N-terminal propeptide, osteocalcin (OC), and alkaline phosphatase levels between the two groups. Multivariate analysis showed that serum P (odds ratio [OR] = 0.989; 95% confidence interval [95% CI] = 0.981–0.996; P = 0.003), serum Ca (OR = 0.007; 95% CI = 0.001–0.415; P = 0.017), serum Ca/P (OR = 0.135; 95% CI = 0.019–0.947; P = 0.044) and OC levels (OR = 1.012; 95% CI = 1.001–1.024; P = 0.036) were predictors of early postoperative SH. The receiver operating characteristic curve analysis revealed that serum P (area under the curve [AUC] = 0.859, P < 0.001), serum Ca/P (AUC = 0.735, P = 0.010) and OC (AUC = 0.729, P = 0.013) had high sensitivity and specificity. Conclusion: Preoperative serum P, serum Ca/P and osteocalcin levels may identify patients with PHPT at risk for early postoperative SH after PTX. [ABSTRACT FROM AUTHOR]

Stimuli‐responsive hydrogels that leverage protein conformational changes are of significant interest in the design of dynamic materials applicable in a myriad of fields, such as drug delivery, actuators, biosensors, and microfluidics. The small calcium binding protein calmodulin (CaM), which undergoes three‐stage conformational changes upon successive binding with Ca2+ and specific ligands, offers a mechanism to create dynamic hydrogels with three distinct physical states. In this work, a CaM‐based recombinant protein hydrogel is engineered using [Ru(bpy)3]2+‐mediated photo‐crosslinking. This hydrogel displays the ability to reversibly increase its Young's modulus by 1.5‐fold and ∼7‐fold, respectively, upon binding with Ca2+ and subsequent interaction with trifluoperazine. The magnitude of stiffness changes is tunable by adjusting the length proportion of dynamic and static domains and modifying protein content. This tunable and reversible control over hydrogel mechanics is further utilized to engineer shape‐morphing materials, highlighting the versatile potential of this CaM‐based protein hydrogel for diverse applications. [ABSTRACT FROM AUTHOR]

Advancements in nanochemistry have led to the development of engineered gold nanostructures (GNSs) with remarkable potential for a variety of dental healthcare applications. These innovative nanomaterials offer unique properties and functionalities that can significantly improve dental diagnostics, treatment, and overall oral healthcare applications. This review provides an overview of the latest advancements in the design, synthesis, and application of GNSs for dental healthcare applications. Engineered GNSs have emerged as versatile tools, demonstrating immense potential across different aspects of dentistry, including enhanced imaging and diagnosis, prevention, bioactive coatings, and targeted treatment of oral diseases. Key highlights encompass the precise control over GNSs' size, crystal structure, shape, and surface functionalization, enabling their integration into sensing, imaging diagnostics, drug delivery systems, and regenerative therapies. GNSs, with their exceptional biocompatibility and antimicrobial properties, have demonstrated efficacy in combating dental caries, periodontitis, peri-implantitis, and oral mucosal diseases. Additionally, they show great promise in the development of advanced sensing techniques for early diagnosis, such as nanobiosensor technology, while their role in targeted drug delivery, photothermal therapy, and immunomodulatory approaches has opened new avenues for oral cancer therapy. Challenges including long-term toxicity, biosafety, immune recognition, and personalized treatment are under rigorous investigation. As research at the intersection of nanotechnology and dentistry continues to thrive, this review highlights the transformative potential of engineered GNSs in revolutionizing dental healthcare, offering accurate, personalized, and minimally invasive solutions to address the oral health challenges of the modern era. [ABSTRACT FROM AUTHOR]

Background: Previous studies suggested higher serum progesterone (P) levels were strongly associated with a lower clinical pregnancy rate (CPR) for in vitro fertilization-embryo transfer (IVF-ET). However, the effect of increased serum P levels on the day of human chorionic gonadotropin (hCG) administration on clinical outcomes in short-acting gonadotropin-releasing hormone agonist (GnRHa) downregulated IVF-ET cycles remains unclear.Methods: We conducted a retrospective cohort study from January 2017 to December 2021, which included a total of 1664 patients receiving their first short-acting GnRHa IVF-ET cycles at our reproductive medicine centre of Nanjing Drum Tower Hospital. The smooth curve fitting and interaction analysis were employed to analyse the association between the CPR and the serum P levels with different embryo types (cleavage-stage embryo or blastocyst). In addition, total cycles were grouped according to different P levels on the trigger day of hCG administration for further analysis.Results: The CPR of patients with increased serum P level (higher than 1.5 ng/mL) on the hCG day did not decrease. A smoothing curve fitting showed that the CPR did not change obviously with the increase in serum P levels. Subgroup analysis of different types of embryos transferred showed that no correlation was observed between the CPR and serum P levels on the day of hCG administration in cleavage-stage embryo transfer cycles. However, the CPR of patients receiving blastocyst transfer showed a downward trend with the increase in serum P levels. At the same time, an interaction analysis also confirmed that the CPR of blastocyst transfer was more likely to be affected by elevated serum P levels on the hCG day.Conclusion: In the luteal phase short-acting GnRHa downregulated IVF-ET cycles, the elevated serum P levels on the hCG day did not affect the CPR of cleavage-stage embryo transfer but reduced the CPR of blastocyst transfer. [ABSTRACT FROM AUTHOR]

Background: To measure total type 1 serum amino-terminal propeptide procollagen (t-P1NP), β- type 1 cross-linked C-terminal telopeptide collagen (β-CTX), N-terminal osteocalcin (OC), and 25-(OH)-VD3 levels before parathyroidectomy (PTX) in patients with PHPT, and correlate these measurements with bone mineral density (BMD) changes at 1-year post-PTX. Methods: Patients with primary hyperparathyroidism (PHPT) were followed from diagnosis to 12 months after surgery. Serum levels of calcium, parathyroid hormone (PTH), vitamin 25-(OH)-VD3, OC, β-CTX, t-P1NP, and BMD were measured before and 1 year after surgery. Results: One year after PTX, mean BMD increased by 25.7, 27.7, and 33.5% in the lumbar spine (L1-L4), femoral neck (FN), and greater trochanter (GT), respectively. Percent BMD change 1-year post-PTX was significant correlated with preoperative levels of β-CTX (L1-L4: r = 0.41, P < 0.0001; FN: r = 0.54, P = 0.0003; GT: r = 0.46, P = 0.0029), t-P1NP (L1-L4: r = 0.58, P < 0.0001; FN: r = 0.73, P < 0.0001; GT: r = 0.65, P < 0.0001), 25-(OH)-VD3 (L1-L4: r = −0.33, P = 0.034; FN: r = −0.48, P = 0.002; GT: r = −0.52, P = 0.0007), and OC (L1-L4: r = 0.49, P = 0.0013; FN: r = 0.55, P = 0.0002; GT: r = 0.47, P = 0.002). Conclusions: Preoperative levels of turnover markers and BMD improvements were significantly correlated in patients with PHPT 1 year after PTX. [ABSTRACT FROM AUTHOR]

Vocabulary plays a critical role in later reading achievement of emergent bilingual children (EBC) who are learning two languages. Given emerging vocabulary intervention research for EBC, we synthesize studies on vocabulary interventions designed for preschool and kindergarten EBC to provide the cumulative knowledge on the following dimensions: (a) EBC's characteristics, (b) features of selected target words and books, (c) critical components of vocabulary interventions, and (d) the overall effectiveness of the interventions as reflected by the percentage of studies reporting a significant increase on proximal measures of EBC's target words. Through a systematic search, we identified 19 articles using experimental or quasi-experimental designs. Overall, EBC increased their knowledge of words taught through vocabulary instruction, and the use of bilingual or family heritage instructional language increased EBC's vocabulary knowledge in both languages. [ABSTRACT FROM AUTHOR]

Objective: Dose an elevated serum progesterone (P) level on the human chorionic gonadotropin (hCG) trigger day have a negative effect on clinical pregnancy outcomes for embryos transferred at different stages of development in long-acting gonadotropin-releasing hormone agonist (GnRHa) in vitro fertilization-embryo transfer (IVF-ET) cycles?Study Design: This was a noninterventional, retrospective, observational, single-centre cohort study. A total of 1951 patients received long-acting GnRHa for pituitary downregulation in IVF-ET cycles at Nanjing Drum Tower Hospital from January 2018 to December 2020. The serum P levels on the day of hCG administration were measured, together with other cycle parameters, to explore the relationship between P levels and the clinical pregnancy rate (CPR) of different embryos transferred.Results: When the serum P level on the hCG day was higher than 1.5 ng/mL, the CPR did not decrease significantly. There was no correlation between the CPR of cleavage-stage embryo transfer and the serum P level on the hCG day. In addition, the interaction analysis suggested that the CPR of patients undergoing blastocyst transfer decreased as serum P levels on the hCG day increased. Progesterone levels on the day of hCG administration were closely related to the CPR of blastocyst transfer rather than cleavage-stage embryo transfer.Conclusion: An increased serum P level on the day of hCG administration did not affect the CPR of cleavage-stage embryo transfer, but it reduced the CPR of blastocyst transfer cycles. [ABSTRACT FROM AUTHOR]

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH‐sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria‐mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A‐activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5‐fluorouracil (5‐FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft‐bearing mice that have a low response rate to 5‐FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor‐specific microenvironment‐activatable systems. [ABSTRACT FROM AUTHOR]

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH‐sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria‐mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A‐activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5‐fluorouracil (5‐FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft‐bearing mice that have a low response rate to 5‐FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor‐specific microenvironment‐activatable systems. [ABSTRACT FROM AUTHOR]

Background: This study aimed to explore the relationship between serum oestrogen (E2) levels before endometrial transformation and pregnancy outcomes of hormone replacement therapy-frozen embryo transfer (HRT-FET) cycles, which has been investigated for years without any consensus.Methods: A retrospective cohort study of 10,209 cycles HRT-FET cycles was conducted at the Reproductive Medicine Center of Nanjing Drum Tower Hospital from March 2017 to December 2020. A smooth fitting curve was constructed to identify the relationship between serum E2 levels before endometrial transformation and the clinical pregnancy rate. Then, threshold and saturation effect analysis was employed to explore the cut-off value of serum E2 levels. In addition, patients were divided into 2 groups based on their levels of serum E2 measured before progesterone-induced endometrial transformation: Group 1, < 300 pg/mL (n = 6251) and Group 2, ≥ 300 pg/mL (n = 3958). The clinical pregnancy and miscarriage rates of all groups were compared. Further smooth fitting curve analysis was employed by different subgroups segmented according to different endometrial thicknesses.Results: When the serum E2 level was greater than 300 pg/mL, the clinical pregnancy rate decreased significantly (62.9% vs. 59.8%, p < 0.01), but the miscarriage rates were similar (13.5% vs. 15.6%, p = 0.14). While serum E2 level reached or exceeded 1400 pg/mL, there was no significant correlation between the clinical pregnancy rate and E2 level. The clinical pregnancy rate reached its higher level at lower E2 levels, regardless of the different endometrail thicknesses.Conclusions: Patients with a lower pretransformation serum E2 level (less than 300 pg/mL) have a higher clinical pregnancy rate and there was no correlation between the clinical pregnancy rate and a higher serum E2 level (greater than 1400 pg/mL) in HRT-FET cycles. [ABSTRACT FROM AUTHOR]

Temperature monitoring in vivo plays a vital role in the investigation of biological processes of organisms and the improvement of disease theranostic methods. The development of lanthanide luminescent nanocomposite‐derived temperature probes in vivo allows accurate and reliable interrogation of biological thermodynamic processes due to their superior photostability, high sensitivity, and non‐invasive sensing fashion. This concept presented an overview of the recent development of lanthanide luminescent nanocomposite which are suitable for in vivo temperature monitoring, including the thermometric principles, key features, materials designs as well as their potential biomedical applications for non‐invasive temperature detection in the living body. The perspectives of these lanthanide luminescent nanocomposite thermometers for the optimization of temperature monitoring performance and potential future development are also discussed. [ABSTRACT FROM AUTHOR]

Exosomes, a type of extracellular vesicles, have attracted considerable attention due to their ability to provide valuable insights into the pathophysiological microenvironment of the cells from which they originate. This characteristic implicates their potential use as diagnostic disease biomarkers clinically, including cancer, infectious diseases, neurodegenerative disorders, and cardiovascular diseases. Aptasensors, which are electrochemical aptamers based biosensing devices, have emerged as a new class of powerful detection technology to conventional methods like ELISA and Western analysis, primarily because of their capability for high performance bioanalysis. This review covers the current research landscape on the detection of exosomes utilizing nanoarchitectonics strategy for the development of electrochemical aptasensors. Strategies involving signal amplification and biofouling prevention are discussed, with an emphasis on nanoarchitectonics-based bio-interfaces, showcasing their potential to enhance sensitivity and selectivity through optimal conduction and mass transport properties. The ongoing challenges to broaden the clinical applications of these biosensors are also highlighted. [ABSTRACT FROM AUTHOR]

The American School Counselor Association (ASCA) requires that school counselors engage with and advocate for students with emotional and behavioral disorders (EBD), in addition to requiring competency in counseling culturally and linguistically diverse (CLD) students. However, few publications have called for increased attention to the intersectional needs of this population. This column provides a brief rationale for focusing on students with EBD who are also CLD and recommends a trauma-informed approach to supporting them through fostering a safe school-wide environment, building faculty and staff cultural competence, increasing collaborative communication with students and families, and recommending counseling services in individualized education program meetings. [ABSTRACT FROM AUTHOR]

A tenet of the Multi-Tiered System of Supports (MTSS) is that even evidence-based interventions will not be effective with all children. We examined preschool children's response to a supplemental literacy intervention (Story Friends) in two classrooms. Children with weak vocabulary skills were identified and received the intervention. The extremes in children's response to Story Friends ranged from highly effective to very ineffective. In one classroom, three children who were not responsive to Story Friends received additional intervention components. Two of these children acquired new vocabulary words at rates comparable to highly responsive peers receiving Story Friends only, and greater than peers in both classrooms not receiving additional support. The third child was dropped due to refusal to attend sessions. Children's lack of learning the control words demonstrated that their progress on the taught words was not due simply to listening to the words read in the stories. [ABSTRACT FROM AUTHOR]

Background: The use of health care services is influenced by various factors, including demographic, social, economic, and health status factors. This study aimed to identify the factors that influence health care use in health insurance subscribers and medical aid beneficiaries in Korea.Methods: A total of 11,793 subjects were identified, including 10,838 health insurance subscribers and 955 medical aid beneficiaries, using the Korea Welfare Panel Study database. The data were analysed by percentage, t-test, and multiple regression using SPSS 20.0.Results: Medical aid beneficiaries had 13.51 more days of outpatient visits and 8.38 more days of hospitalization compared with health insurance subscribers. Factors affecting the frequency of outpatient visits for health insurance subscribers were gender, age, household type, education level, income level, administrative district, perceived health status, chronic disease, and disability. These factors accounted for 19.8% of explanation (p < .001). Whereas, gender, household type, administrative district, perceived health status, and chronic disease were identified as factors influencing outpatient frequency for medical aid beneficiaries. These factors accounted for 11.2% of explanation (p < .001). For health insurance subscribers, factors affecting the length of hospitalization were gender, public pension status, place of residence, administrative district, economic activity, income level, perceived health status, and disability status. These factors accounted for 7.2% of explanation (p < .001). While, factors affecting the length of hospitalization for medical aid beneficiaries were accounted for by 3.4% (p < .001). Gender and perceived health status were identified as factors influencing the length of hospitalization of medical aid beneficiaries.Conclusions: There were differences between medical aid beneficiaries and health insurance subscribers in health care use and influencing factors. Future management programs should take into consideration the specific factors that influence the use of health care services in health insurance subscribers and medical aid beneficiaries. [ABSTRACT FROM AUTHOR]

A unique cuboid spider silk from the outer egg sac of Nephila pilipes, with an unusual square cross‐section, is disclosed. The structure–function relationships within this silk are first studied through structural characterization, mechanical measurement, protein conformation, and polypeptide signature of silk proteins. This silk maintains the higher stiffness property of egg sac silks, and also shows a species difference. Environmental response of the mechanical properties within this silk are observed. Synchrotron FTIR microspectroscopy is used to monitor the silk protein conformation in a single natural silk. The β‐sheet structure aligns parallel to the fiber axis with a content of 22% ± 2.6%. The de novo resulting polypeptide from the solid silk fibers are novel, and an abundant polar amino acid insertion is observed. Short polyalanine (An, n ≤ 3), alternating serine and alanine (S/A)X, and alternating glycine and alanine (G/A)X, GGX, and SSX dominates in the resulting de novo polypeptide. This accords with the composition pattern of other egg sac silk proteins, besides the rarely observed GGX. This study broadens the library of egg sac spider silks and provides a new perspective to uncover structure–function relationships in spider silk. [ABSTRACT FROM AUTHOR]

The emergence of novel two-dimensional (2D) monoelemental materials (Xenes) has shown remarkable potential for their applications in different fields of technology, as well as addressing new discoveries in fundamental science. Xenes (e.g., borophene, silicene, germanene, stanene, phosphorene, arsenene, antimonene, bismuthene, and tellurene) are of particular interest because they are the most chemically tractable materials for synthetic exploration. Owing to their excellent physical, chemical, electronic and optical properties, Xenes have been regarded as promising agents for biosensors, bioimaging, therapeutic delivery, and theranostics, as well as in several other new bio-applications. In this tutorial review, we summarize their general properties including the classification of Xenes according to their bulk properties. The synthetic and modification methods of Xenes are also presented. Furthermore, the representative Xene nanoplatforms for various biomedical applications are highlighted. Finally, research progress, challenges, and perspectives for the future development of Xenes in biomedicines are discussed. [ABSTRACT FROM AUTHOR]

Background. The main objective of this meta-analysis was to investigate whether remote ischemic preconditioning (RIPC) reduces cardiac and renal events in patients undergoing elective cardiovascular interventions. Methods and Results. We systematically searched articles published from 2006 to 2016 in PubMed, EMBASE, Web of Science, Cochrane Library, and Google Scholar. Odds ratios (ORs) with 95% confidence intervals (CIs) were used as the effect index for dichotomous variables. The standardized mean differences (SMDs) with 95% CIs were calculated as the pooled continuous effect. Sixteen RCTs of 2435 patients undergoing elective PCI were selected. Compared with control group, RIPC could significantly reduce the incidence of perioperative myocardial infarction (OR = 0.64; 95% CI: 0.48–0.86; P=0.003) and acute kidney injury (OR = 0.56; 95% CI: 0.322–0.99; P=0.049). Metaregression analysis showed that the reduction of PMI by RIPC was enhanced for CAD patients with multivessel disease (coef.: −0.05 [-0.09;-0.01], P=0.022). There were no differences in the changes of cTnI (P=0.934) and CRP (P=0.075) in two groups. Conclusion. Our meta-analysis of RCTs demonstrated that RIPC can provide cardiac and renal protection for patients undergoing elective PCI, while no beneficial effect on reducing the levels of cTnI and CRP after PCI was reported. [ABSTRACT FROM AUTHOR]

As a 2D nanomaterial, MXene (Ti 3 C 2 T x) has shown enormous potential for use in fields such as biomedical and environmental pollution. However, the utilization of MXene materials in plants has received little attention thus far. The efficient use of MXene materials in agriculture and forestry is first highlighted in this study. Phenotypic and physiological analyses indicated that MXene application significantly enhanced the tolerance of Torreya grandis to Pb stress by reducing Pb accumulation. Furthermore, we illustrated two independent mechanisms of MXene material in reducing Pb accumulation in T. grandis : 1) MXene converted the available form of Pb into stable forms via its strong Pb adsorption ability, resulting in a decrease of the available form of Pb in soils, and 2) MXene application obviously increased the cell wall pectin content to restrict more Pb in the cell wall by regulating the expression of pectin synthesis/metabolism-related genes (TgPLL2 , TgPLL11 , TgPG5 , TgPG30 , TgGAUT3 and TgGAUT12) in T. grandis roots. Overall, this finding provides insight into the application of MXene material in modern agriculture and forestry, which will facilitate the rapid development of nanotechnology in sustainable agriculture and forestry. [Display omitted] • MXene application enhances the tolerance of Torreya grandis to Pb stress. • MXene application reduces the accumulations of Pb in T. grandis. • MXene converts the available Pb to stable Pb via its strong Pb adsorption ability. • MXene application increases the pectin content to restrict more Pb in cell wall. [ABSTRACT FROM AUTHOR]

Ultrasensitive determination of the chiral nature of a molecule is important for fully understanding protein and DNA structures, and for the design, synthesis and purification of drug molecules. Consequently, development of ultrasensitive detection of chiral molecules is a grand challenge and at the heart of many of today’s research fields, including chemistry, biology, biotechnology and pharmacology. Here a novel method afforded by electrochemically tracing the Cu 2+ ions that are replaced by L/D -carnitine on an L/D -cysteine modified gold electrode is described. The electrochemical signal of copper ionswas monitored, these were immobilized on the L/D -cysteine functionalized gold electrode surface via cooperative metal-ligand interaction, followed by replacing the Cu 2+ with L -carnitine or D -carnitine chiral molecules based on the hetero- or homo- chiral interaction between carnitine and cysteine molecules. The results illustrated that the Cu 2+ replacement ratio between L/D -carnitine and D/L -cysteine were higher than that between L/D -carnitine and L/D -cysteine, which is consistent with previous studies that hetero-chiral interaction is stronger than homo-chiral interaction. This study demonstrates a facile, but innovative electrochemical method to probe the chiral recognition of carnitine molecules. [ABSTRACT FROM AUTHOR]

In this paper, the influence of chemically reduced graphene oxide sheets (CRGOs) on the electrochemical performance through methyl or carboxylic acid terminated self-assembled monolayers (SAMs) is reported. The gold electrode was initially modified with methyl or carboxylic acid terminated alkanethiols with various carbon chain lengths (n = 4, 6, 8 and 11) and subsequently immobilization of the CRGOs on a SAM surface was achieved via a hydrophobic and electrostatic interaction. By using the potassium ferricyanide as a redox probe, it was observed that CRGOs could effectively enhance the heterogeneous electron transfer (ET) of the SAM due to a tunneling effect. The assemblies based on thiol end groups with methyl head groups were observed to afford more hydrophobic interaction binding with CRGOs with a higher reduction time than the assemblies developed with thiol end groups and a −COOH group which were shown to bind more electrostatically with CRGOs, a lowering reduction time. The Nyquist plots developed show a gradual decrease of the charge transfer resistance ( R ct ) of [Fe(CN) 6 ] 3−/4− redox couple at the CRGOs-SAMs electrode with the controllable adsorption of different CRGO’s onto the SAM. Depending on the chain length and terminal functional group the electron transfer rate kinetics were observed to differ considerably. [ABSTRACT FROM AUTHOR]

Two pure dehydrated borogermanates with microporous structure, β -K 2 [B 2 Ge 3 O 10 ] and NH 4 [BGe 3 O 8 ], have been synthesized and characterized by XRD, FT-IR, TG techniques. The molar enthalpies of solution of 2.51 mg of GeO 2 (s)/0.99 mg of H 3 BO 3 (s)/1.98 mg of H 3 BO 3 (s) in 2.00 cm 3 of 1 mol · dm −3 NaOH (aq) were measured, respectively. The molar enthalpies of solution of 2.44 mg of K 2 B 4 O 7 · 4H 2 O (s) and 2.18 mg of NH 4 B 5 O 8 · 4H 2 O (s) in the mixture solvent of 2.00 cm 3 of 1 mol · dm −3 NaOH (aq) which contains 2.51 mg of GeO 2 (s) were measured, respectively. The molar enthalpies of solution of 3.82 mg of β -K 2 [B 2 Ge 3 O 10 ] (s) in the mixture solvent of 2.00 cm 3 of 1 mol · dm −3 NaOH (aq) which contains 0.99 mg of H 3 BO 3 (s), and 3.00 mg of NH 4 [BGe 3 O 8 ] (s) in the mixture solvent of 2.00 cm 3 of 1 mol · dm −3 NaOH (aq) which contains 1.98 mg of H 3 BO 3 ) (s) were also measured, respectively. With the use of standard molar enthalpies of formation for NH 4 B 5 O 8 · 4H 2 O (s), K 2 B 4 O 7 · 4H 2 O (s), GeO 2 (s), H 3 BO 3 (s) and H 2 O (l), the standard molar enthalpies of formation of – (3937.1 ± 4.7) kJ · mol −1 for β -K 2 [B 2 Ge 3 O 10 ] and – (2713.7 ± 6.0) kJ · mol −1 for NH 4 [BGe 3 O 8 ] at T = 298.15 K were obtained on the basis of the appropriate thermochemical cycles, respectively. [ABSTRACT FROM AUTHOR]

We describe an alternative electrochemical technique to monitor covalent bond formation in real-time using nanoparticle–electrode collisions. The method is based on recognising the redox current when MP-11 functionalised chemical reduced graphene oxide (rGO) nanosheets collide with Lomant's reagent modified gold microelectrode. This facile and highly sensitive monitoring method can be useful for investigating the fundamental of single-molecule reactions. [ABSTRACT FROM AUTHOR]

Due to their potential biomedical applications, protein-based hydrogels have attracted considerable interest. Although various methods have been developed to engineer self-assembling, physically-crosslinked protein hydrogels, exploring novel driving forces to engineer such hydrogels remains challenging. Protein fragment reconstitution, also known as fragment complementation, is a self-assembling mechanism by which protein fragments can reconstitute the folded conformation of the native protein when split into two halves. Although it has been used in biophysical studies and bioassays, fragment reconstitution has not been explored for hydrogel construction. Using a small protein GL5 as a model, which is capable of fragment reconstitution to reconstitute the folded GL5 spontaneously when split into two halves, GN and GC, we demonstrate that protein fragment reconstitution is a novel driving force for engineering self-assembling reversible protein hydrogels. Fragment reconstitution between GN and GC crosslinks GN and GC-containing proteins into self-assembling reversible protein hydrogels. These novel hydrogels show temperature-dependent reversible sol-gel transition, and excellent property against erosion in water. Since many proteins can undergo fragment reconstitution, we anticipate that such fragment reconstitution may offer a general driving force for engineering protein hydrogels from a variety of proteins, and thus significantly expanding the 'toolbox' currently available in the field of biomaterials. [ABSTRACT FROM AUTHOR]

Covalently immobilized poly(4-vinylphenol) (PVP) monolayer films were fabricated by spin coating PVP on perfluorophenyl azide (PFPA)-functionalized surfaces followed by UV irradiation. The pH-responsive behavior of these PVP ultrathin films was evaluated by ellipsometry, quartz crystal microbalance (QCM) and surface plasmon resonance (SPR). By monitoring the responses of these films to pH in situ , the ionization constant of the monolayer thin films was obtained. The apparent p K a value of these covalently immobilized PVP monolayers, 13.4 by SPR, was 3 units higher than that of the free polymer in aqueous solution. [ABSTRACT FROM AUTHOR]

Carbohydrate–functionalized single-walled carbon nanotubes (SWNTs) were synthesized using microwave-assisted reaction of perfluorophenyl azide with the nanotubes. The results showed that microwave radiation provides a rapid and effective means to covalently attach carbohydrates to SWNTs, producing carbohydrate–SWNT conjugates for biorecognition. The carbohydrate–functionalized SWNTs were furthermore shown to interact specifically with cognate carbohydrate-specific proteins (lectins), resulting in predicted recognition patterns. The carbohydrate-presenting SWNTs constitute a new platform for sensitive protein- or cell recognition, which pave the way for glycoconjugated carbon nanomaterials in biorecognition applications. [ABSTRACT FROM AUTHOR]

Protein hydrogels have attracted considerable interest due to their potential applications in biomedical engineering. Creating protein hydrogels with dynamic mechanical properties is challenging. Here, the engineering of a novel, rationally designed protein-hydrogel is reported that translates molecular level protein folding-unfolding conformational changes into macroscopic reversibly tunable mechanical properties based on a redox controlled protein folding-unfolding switch. This novel protein folding switch is constructed from a designed mutually exclusive protein. Via oxidation and reduction of an engineered disulfide bond, the protein folding switch can switch its conformation between folded and unfolded states, leading to a drastic change of protein's effective chain length and mechanical compliance. This redox-responsive protein can be readily photochemically crosslinked into solid hydrogels, in which molecular level conformational changes (folding-unfolding) can result in significant macroscopic changes in hydrogel's physical and mechanical properties due to the change of the effective chain length between two crosslinking points in the protein hydrogel network. It is found that when reduced, the hydrogel swells and is mechanically compliant; when oxidized, it swells to a less extent and becomes resilient and stiffer, exhibiting an up to fivefold increase in its Young's modulus. The changes of the mechanical and physical properties of this hydrogel are fully reversible and can be cycled using redox potential. This novel protein hydrogel with dynamic mechanical and physical properties could find numerous applications in material sciences and tissue engineering. [ABSTRACT FROM AUTHOR]

In this study, the modification of basal planes of highly oriented pyrolytic graphite (HOPG) electrodes with pyrene-functionalised biotin (PFB), via π-π stacking, and ethylene glycol antifouling molecules, via covalent bonding, for detection of streptavidin is presented. Biotin was first conjugated to the pyrene moieties by an esterification reaction in order to enable the self-assembly of biotin onto the surface of HOPG via non-covalent π-π stacking. The as-prepared biotinylated electrode was used as the sensing probe to analyze the concentration of streptavidin via the diminution in pyrene electrochemistry resulted from the desorption of pyrene from the surface that is mediated by the biotin-streptavidin recognition. X-ray photoelectron spectroscopy (XPS), cyclic voltammetry (CV), square wave voltammetry (SWV) measurements, and electrochemical impedance spectroscopy (EIS) were used to characterize the amount of surface bound pyrene modified biotin and the concentration of streptavidin. This simple strategy can be applied to the detection of other biomolecules via bio-recognition and the reversible π-π stacking process. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate the clinical utility of serum luteinizing hormone (LH) level in predicting frozen embryo transfer (FET) outcomes among the patients with an ovulation induction (OI) cycle. Methods: A total of 250 patients who underwent OI cycle frozen–thawed embryo transfer from January 2018 to June 2020 in Drum Tower Hospital affiliated with Nanjing University Medical School were retrospectively analyzed. The primary outcomes were clinical pregnancy rate and the live birth rate. Results: The results showed that a significant difference in Serum LH level on the day of human chorionic gonadotropin (hCG) administration was observed between the clinical pregnancy group and no clinical pregnancy group (p = 0.002), while there was no significant difference between the live birth group and no live birth group (p = 0.06). Multiple logistic regression analysis of factors related to clinical pregnancy showed serum LH level on the day of hCG administration was related to improved clinical pregnancy rate (OR was 1.02, 95% CI: 1.0–1.03, p = 0.02), while serum LH level had no significant effect on live birth rate. The ROC curves revealed the serum LH level was significantly correlated with clinical pregnancy rate and live birth rate; the cut-off point of serum LH level on the day of hCG administration was 8.46 miu/mL for clinical pregnancy rate (AUC 0.609, p = 0.003). Conclusion: In patients with OI FET, serum LH level on the day of hCG administration might be a biomarker for the prediction of clinical pregnancy. The prediction that patients who underwent OI cycle frozen–thawed embryo transfer with serum LH levels below 8.46 mIU /mL might be pregnant appeared to be meaningful. [ABSTRACT FROM AUTHOR]

DNA Damage Response, DNA Repair, Drug Delivery, Floxuridine, Protein Phosphatase 2A Keywords: DNA Damage Response; DNA Repair; Drug Delivery; Floxuridine; Protein Phosphatase 2A EN DNA Damage Response DNA Repair Drug Delivery Floxuridine Protein Phosphatase 2A 1 1 1 04/06/22 20220411 NES 220411 B Reaktionen auf DNA-Schäden b , welche die DNA-Reparatur und Zellzykluskontrollpunkte in Krebszellen involvieren, gelten als eines der Haupthindernisse für die traditionelle Chemotherapie. Die Ergebnisse zeigen, dass die DNA-Schadensreparaturwege während der 5-FU/FUDR-Therapie eine entscheidende Rolle spielen, und sie unterstreichen die Bedeutung der Hemmung dieser Wege für die Sensibilisierung von Krebszellen gegenüber Chemotherapeutika. [Extracted from the article]

We report a novel multifunctional construct, M1, designed explicitly to target the DNA damage response in cancer cells. M1 contains both a floxuridine (FUDR) and protein phosphatase 2A (PP2A) inhibitor combined with a GSH‐sensitive linker. Further conjugation of the triphenylphosphonium moiety allows M1 to undergo specific activation in the mitochondria, where mitochondria‐mediated apoptosis is observed. Moreover, M1 has enormous effects on genomic DNA ascribed to FUDR's primary function of impeding DNA/RNA synthesis combined with diminishing PP2A‐activated DNA repair pathways. Importantly, mechanistic studies highlight the PP2A obtrusion in FUDR/5‐fluorouracil (5‐FU) therapy and underscore the importance of its inhibition to harbor therapeutic potential. HCT116 cell xenograft‐bearing mice that have a low response rate to 5‐FU show a prominent effect with M1, emphasizing the importance of DNA damage response targeting strategies using tumor‐specific microenvironment‐activatable systems. [ABSTRACT FROM AUTHOR]

Deficiency or mutation in the p53 tumor suppressor gene commonly occurs in human cancer and can contribute to disease progression and chemotherapy resistance. Currently, although the pro-survival or pro-death effect of autophagy remains a controversial issue, increasing data seem to support the idea that autophagy facilitates cancer cell resistance to chemotherapy treatment. Here we report that 5-FU treatment causes aberrant autophagosome accumulation in HCT116 p53−/− and HT-29 cancer cells. Specific inhibition of autophagy by 3-MA, CQ or small interfering RNA treatment targeting Atg5 or Beclin 1 can potentiate the re-sensitization of these resistant cancer cells to 5-FU. In further analysis, we show that JNK activation and phosphorylation of Bcl-2 are key determinants in 5-FU-induced autophagy. Inhibition of JNK by the compound SP600125 or JNK siRNA suppressed autophagy and phosphorylation of c-Jun and Bcl-2 but increased 5-FU-induced apoptosis in both HCT116 p53−/− and HT29 cells. Taken together, our results suggest that JNK activation confers 5-FU resistance in HCT116 p53−/− and HT29 cells by promoting autophagy as a pro-survival effect, likely via inducing Bcl-2 phosphorylation. These results provide a promising strategy to improve the efficacy of 5-FU-based chemotherapy for colorectal cancer patients harboring a p53 gene mutation. [ABSTRACT FROM AUTHOR]

Two new flavonoid glycosides, named quercetin-3-O-(2″-O-tigloyl)-α-l-rhamnopyranoside (1) and quercetin-3-O-(3″-O-tigloyl)-α-l-rhamnopyranoside (2), together with 10 known flavonoids (3–12), were isolated from the whole plant of the halophyteLimonium franchetii. Their structures were elucidated on the basis of extensive spectroscopic analysis including 2D NMR and HR-EI-MS. In addition, primary bioassays showed that compound1had moderate cytotoxic activity against rat C6 glioma cell lines. [ABSTRACT FROM PUBLISHER]

Abstract: The Mitogen Activated Protein Kinase (MAPK) signaling plays a critical role in the outcome and the sensitivity to anticancer therapies. Activated MAPK can transmit extracellular signals to regulate cell growth, proliferation, differentiation, migration, apoptosis and so on. Apoptosis as well as macroautophagy (hereafter referred to as autophagy) can be induced by extracellular stimuli such the treatment of chemotherapeutic agents, resulting in different cell response to these drugs. However, the molecular mechanisms mediating these two cellular processes remain largely unknown. Recently, several studies provide new insights into p38 and JNK MAPK pathways function in the control of the balance of autophagy and apoptosis in response to genotoxic stress. Our increased understanding of the role of p38 and JNK MAPK pathways in regulating the balance of autophagy and apoptosis will hopefully provide prospective strategies for cancer therapy. [Copyright &y& Elsevier]

The influence of graphene on the electrical communication through organic layers fabricated on graphite and gold electrodes is investigated. These layers were prepared by in situ reductive adsorption of 4-aminobenzoic acid in the presence of NaNO2 and HCl to have surface bound carboxylic acid functionalities, followed by covalent attachment of 1-aminopyrene via an amide coupling reaction to have surface bound pyrene groups for graphene immobilization via noncovalent ππ stacking interaction. The coverage of the layers created via reductive adsorption on graphite electrodes was found to be much higher than that on gold electrodes. It was revealed that graphene significantly enhances the electrical communication through the layers on graphite electrodes but on gold electrodes the enhancement effect through the layers was only minor. However, when gold electrodes were modified with a self-assembled monolayer (SAM) of propanethiol the subsequent immobilization of graphene resulted in a significant enhancement of the electrical communication. It is also found that immobilization of graphene could affect the electron transfer between the redox probe, pyrene and the underlying electrodes. Atomic force microscopy (AFM) and scanning electron microscopy (SEM) were used to characterize the graphene sheets. Cyclic voltammetry, electrochemical impedance spectroscopy (EIS), and X-ray photoelectron spectroscopy (XPS) were also used to characterize the stepwise modified electrodes. [ABSTRACT FROM AUTHOR]

The purpose of this article is to synthesize the available studies regarding responsive interaction intervention (RII) for children with or at risk for developmental delays with a focus on six dimensions: (a) the characteristics of participants, (b) the features of RII, (c) the measurement of treatment fidelity, (d) the overall effectiveness of RII as reflected by the percentage of studies reporting significant changes in adult or child outcomes, (e) the measurement of maintenance and generalization of RII effects, and (f) the social validity or level of acceptability. Through a search of articles from 1990 to 2010, the authors identified 26 studies (31 articles) employing group experimental or quasiexperimental designs incorporating these dimensions. Overall, the results of the reviewed studies indicated that implementation of RII resulted in significant positive changes in adults’ responsive behaviors and children’s emotional and social-communicative outcomes. Although the most frequently reported child outcomes were in the social-communication domain, the most consistently significant positive outcomes for parent and child outcomes were in the emotional domain. The authors identify several gaps in this literature and suggest areas where research is needed. [ABSTRACT FROM PUBLISHER]

The fabrication of glucose oxidase (GOx) enzyme electrodes with controlled alternate enzyme and graphene layers is described. GOx was first modified with pyrene functionalities in order to be self-assembled onto a graphene basal plane via non-covalent π–π stacking interaction. Fluorescence spectroscopy analysis revealed that about 5.4 pyrene functional groups were attached to each GOx and the pyrene functionalized GOx retained more than 76% of the biocatalytical activity compared with the native enzyme. Via alternate layer-by-layer self-assembly of graphene and pyrene functionalized GOx, mono- and multi-layered enzyme electrodes with controlled biocatalytical activity can be easily fabricated. The biocatalytical activity of the as-prepared enzyme electrodes increased with increasing graphene and GOx layers and increased insignificantly when the layers reached four. Such multi-layered enzyme electrodes with controlled nanostructure exhibited reliable application in human serum samples analysis with high detection sensitivity, good stability and repeatability. A broad linear detection limit of 0.2 to 40 mM was obtained. [ABSTRACT FROM AUTHOR]

Abstract: A gold electrode modified with graphene via non-covalent interaction for a chemical sensor is presented. The gold electrode was first modified with carboxylic acid functionalities, followed by the immobilization of pyrene groups via the esterification reaction. The freshly prepared graphene nanosheets were then attached on the electrode surface via π–π stacking interaction for the analysis of Cu2+ and Pb2+. The graphene modified gold electrode exhibited enhanced analytical sensitivity toward Cu2+ and Pb2+. The linear detection range for Cu2+ analysis is 1.5–20nM and Pb2+ is 0.4–20nM. Good reusability and repeatability were also observed. [Copyright &y& Elsevier]

An important consideration in epileptic seizure prediction is proving the existence of a pre-seizure state that can be detected using various signal processing algorithms. In the analyses of intracranial electroencephalographic (EEG) recordings of four epilepsy patients, the short-term changes in the measures of complexity and synchrony were detected before the majority of seizure events across the sample patient population. A decrease in complexity and increase in phase synchrony appeared several minutes before seizure or, sex and the changes were more pronounced in the focal region than in the remote region. This result was also validated statistically using a surrogate data method. [ABSTRACT FROM AUTHOR]

Carbon nanotubes (CNTs) are promising blocks for building advanced yarns with unique structural and functional attributes. However, the complexity of fabrication and high cost has hindered the widespread adoption of CNT yarns. In this study, a rapid and continuous twisting wet spun yarn strategy to produce highly densified CNT yarns is presented. The method involves effectively dispersing CNTs in the surfactant dispersion, swiftly removing the surfactant in the coagulation bath and twisting treatment to effectively improve the density of yarn and the orientation of CNT. Detailed characterizations on the influence of each spinning conditions reveal that twisting treatment significantly enhances the packing density of yarns, improves the orientation of CNTs, and mitigates the impact of impurities on conductivity. The resulting CNT yarns exhibit a remarkable tensile strength of 600 MPa, a Young's modulus of ≈40 GPa, and a high conductivity of 8990 S cm−1. When utilized as a yarn heater, the CNT yarn demonstrates an ultra‐fast electrothermal response of over 1000 °C s−1 at a low operating voltage of 5 V. Impressively, the mechanical properties of CNT yarns show good stability during heating. This study provides a perspective of structural engineering for the large‐scale preparation of high‐performance CNT yarns. [ABSTRACT FROM AUTHOR]

RNA-based therapies have catalyzed a revolutionary transformation in the biomedical landscape, offering unprecedented potential in disease prevention and treatment. However, despite their remarkable achievements, these therapies encounter substantial challenges including low stability, susceptibility to degradation by nucleases, and a prominent negative charge, thereby hindering further development. Chemically modified platforms have emerged as a strategic innovation, focusing on precise alterations either on the RNA moieties or their associated delivery vectors. This comprehensive review delves into these platforms, underscoring their significance in augmenting the performance and translational prospects of RNA-based therapeutics. It encompasses an in-depth analysis of various chemically modified delivery platforms that have been instrumental in propelling RNA therapeutics toward clinical utility. Moreover, the review scrutinizes the rationale behind diverse chemical modification techniques aiming at optimizing the therapeutic efficacy of RNA molecules, thereby facilitating robust disease management. Recent empirical studies corroborating the efficacy enhancement of RNA therapeutics through chemical modifications are highlighted. Conclusively, we offer profound insights into the transformative impact of chemical modifications on RNA drugs and delineates prospective trajectories for their future development and clinical integration. [ABSTRACT FROM AUTHOR]

Transient receptor potential cation channel subfamily M member (TRPM8) is abnormally expressed in many malignant tumors, such as breast cancer and pancreatic cancer, but its expression in gastric cancer (GC) has remained unclear. The present study aimed to detect TRPM8 expression and to explore its clinical significance in GC. Western blotting and immunohistochemistry were used to detect the protein expression of TRPM8 in 134 pairs of GC and adjacent healthy tissues. The association of TRMP8 with the 5-year overall survival rate of patients with GC was assessed using a Cox regression model. TRPM8 protein expression was significantly elevated (P<0.05) in gastric tumor cells (SUN-1, AGS, SNU-5 and NCI-N87) and was significantly associated with tumor diameter (P=0.003), Tumor-Node-Metastasis stage (P=0.003), lymph node metastasis (P=0.001) and cancer cell remote metastasis (P=0.010) in patients with GC. The expression of TRPM8 protein was significantly higher in GC patients with a tumor diameter of ≥2.5 cm. Additionally, TRPM8 protein expression in patients with metastases was significantly higher compared with patients without metastasis. Cox regression analysis revealed that TRPM8 protein expression was an independent risk factor for prognosis (odds ratio, 1.625; 95% CI=0.552-3.128) in patients with GC. In addition, the 5-year overall survival rate of patients with high expression of TRPM8 protein (64.44%) in GC was significantly lower compared with patients with low expression (12.36%). TRPM8 was highly expressed in GC tissues and may promote GC cell proliferation and metastasis in vivo. [ABSTRACT FROM AUTHOR]

Editor's Note: this Article has been retracted; the Retraction Note is available at https://doi.org/10.1038/s41598-021-82870-5. [ABSTRACT FROM AUTHOR]

[Display omitted] • A reactive MD simulation model for moving droplet corrosion is first developed. • The interaction between droplet wetting and corroding on metal is investigated. • A combination of "sliding" and "rolling" movement mechanisms. The corrosion behavior of moving droplet using reactive molecular dynamics simulation, especially the moving droplet induced is studied for the first time to the best of our knowledge. The effect of wetting on corrosion is mainly reflected in the ordered structure. The ordered structure, which promotes efficient interfacial charge transfer. Residues such as water molecules, aggressive ions and hydrogen ions fill copper surface defects. Moreover, the trace charge atoms on the metal surface and the anions in the ordered structure will form a built-in electric field by Coulomb interaction. Furthermore, there is a combination of "sliding" and "rolling" movement mechanisms. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment (TME), yet in situ engineering of TAMs for enhanced tumor immunotherapy remains a significant challenge in translational immuno‐oncology. Here, we report an innovative nanodrug‐delivering‐drug (STNSP@ELE) strategy that leverages two‐dimensional (2D) stanene‐based nanosheets (STNSP) and β‐Elemene (ELE), a small‐molecule anticancer drug, to overcome TAM‐mediated immunosuppression and improve chemo‐immunotherapy. Our results demonstrate that both STNSP and ELE are capable of polarizing the tumor‐supportive M2‐like TAMs into a tumor‐suppressive M1‐like phenotype, which acts with the ELE chemotherapeutic to boost antitumor responses. In vivo mouse studies demonstrate that STNSP@ELE treatment can reprogram the immunosuppressive TME by significantly increasing the intratumoral ratio of M1/M2‐like TAMs, enhancing the population of CD4+ and CD8+ T lymphocytes and mature dendritic cells, and elevating the expression of immunostimulatory cytokines in B16F10 melanomas, thereby promoting a robust antitumor response. Our study not only demonstrates that the STNSP@ELE chemo‐immunotherapeutic nanoplatform has immune‐modulatory capabilities that can overcome TAM‐mediated immunosuppression in solid tumors, but also highlights the promise of this nanodrug‐delivering‐drug strategy in developing other nano‐immunotherapeutics and treating various types of immunosuppressive tumors. [ABSTRACT FROM AUTHOR]

Tumor‐associated macrophages (TAMs) play a critical role in the immunosuppressive solid tumor microenvironment (TME), yet in situ engineering of TAMs for enhanced tumor immunotherapy remains a significant challenge in translational immuno‐oncology. Here, we report an innovative nanodrug‐delivering‐drug (STNSP@ELE) strategy that leverages two‐dimensional (2D) stanene‐based nanosheets (STNSP) and β‐Elemene (ELE), a small‐molecule anticancer drug, to overcome TAM‐mediated immunosuppression and improve chemo‐immunotherapy. Our results demonstrate that both STNSP and ELE are capable of polarizing the tumor‐supportive M2‐like TAMs into a tumor‐suppressive M1‐like phenotype, which acts with the ELE chemotherapeutic to boost antitumor responses. In vivo mouse studies demonstrate that STNSP@ELE treatment can reprogram the immunosuppressive TME by significantly increasing the intratumoral ratio of M1/M2‐like TAMs, enhancing the population of CD4+ and CD8+ T lymphocytes and mature dendritic cells, and elevating the expression of immunostimulatory cytokines in B16F10 melanomas, thereby promoting a robust antitumor response. Our study not only demonstrates that the STNSP@ELE chemo‐immunotherapeutic nanoplatform has immune‐modulatory capabilities that can overcome TAM‐mediated immunosuppression in solid tumors, but also highlights the promise of this nanodrug‐delivering‐drug strategy in developing other nano‐immunotherapeutics and treating various types of immunosuppressive tumors. [ABSTRACT FROM AUTHOR]

PROteolysis TArgeting Chimeras (PROTACs) are an emerging class of promising therapeutic modalities that selectively degrade intracellular proteins of interest by hijacking the ubiquitin‐proteasome system. However, the lack of techniques to efficiently transport these degraders to targeted cells and consequently the potential toxicity of PROTACs limit their clinical applications. Here, a strategy of nanoengineered PROTACs, that is, Nano‐PROTACs, is reported, which improves the bioavailability of PROTACs and maximizes their capacity to therapeutically degrade intracellular oncogenic proteins for tumor therapy. The Nano‐PROTACs are developed by encapsulating PROTACs in glutathione (GSH)‐responsive poly(disulfide amide) polymeric (PDSA) nanoparticles and show that ARV@PDSA Nano‐PROTAC, nanoengineered BRD4 degrader ARV‐771, improves BRD4 protein degradation and decreases the downstream oncogene c‐Myc expression. Benefiting from the GSH‐scavenging ability to amply the c‐Myc‐related ferroptosis and cell cycle arrest, this ARV@PDSA Nano‐PROTACs strategy shows superior anti‐tumor efficacy with a low dose administration and good biocompatibility in vivo. The findings reveal the potential of the Nano‐PROTACs strategy to treat a broad range of diseases by dismantling associated pathogenic proteins. [ABSTRACT FROM AUTHOR]