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We report an innovative synthetic strategy for the generation of polysubstituted indoles from indolines, aryldiazonium salts, and azoles. The methodology encompasses an electrophilic substitution reaction affording C5-indoline intermediates which undergo an iodine-mediated oxidative transformation coupled with C–H functionalization to yield the indole derivatives. [ABSTRACT FROM AUTHOR]

Background: To investigate the optimal dose of pretreated-dexmedetomidine in fentanyl-induced cough (FIC) suppression. Methods: Patients of 180 undergoing elective surgery with general anesthesia, aged 18–65 years, BMI 18.5–30 kg/m2, ASA I or II, were equally randomized into four groups (n = 45) to receive intravenous pretreatment of dexmedetomidine with 0 (group 1), 0.3 (group 2), 0.6 (group 3) and 0.9 (group 4) mcg/kg over 10 mins, respectively. After the pretreatment, all patients were given a 5-s intravenous injection of fentanyl 4 mcg/kg. The symptoms of irritating cough including the severity and onset time were recorded for 1 min after fentanyl injection. General anesthesia induction was completed with midazolam, propofol and cisatracurium, then endotracheal tube or laryngeal mask was inserted and connected to an anesthesia machine. MAP, HR and SpO2 at the beginning of pretreatment (T0), 3 min (T1), 6 min (T2), 9 min (T3) and 12 min (T4) after the beginning of pretreatment were recorded. Side effects of dexmedetomidine, such as bradycardia, hypertension, hypotension, and respiratory depression were also recorded during the course. Results: Totally 168 patients completed the study. The incidences of cough were 52.4, 42.9, 11.9, and 14.3% in groups 1, 2, 3, and 4, respectively, with no significant differences between groups 1 and 2 (P > 0.05) and between groups 3 and 4 (P > 0.05). The incidence and severity of cough in groups 3 and 4 were significantly lower than those in groups 1 and 2 (P < 0.05). Compared to T0, HR at T2 (P < 0.05), T3 (P < 0.01), and T4 (P < 0.01) decreased significantly and MAP at T4 decreased significantly (P < 0.05) in group 4. Bradycardia occurred in 1 case and respiratory depression occurred in 1 case in group 4. Compared to group 1, the onset time of cough in the other 3 groups were delayed significantly (P < 0.05). Conclusion: Pretreated dexmedetomidine 0.6 mcg/kg blous intravenous infusion over 10 mins could reduce FIC effectively without side effects. Trial registration: This study was registered in ClinicalTrials.gov (NCT03126422), April 13, 2017. [ABSTRACT FROM AUTHOR]

A directing-group-free strategy for oxidative regioselective aminochalcogenation of indolines with amines and dichalconides is presented. This strategy combines tandem coupling sequences and oxidative dehydrogenation methods in a multi-component reaction, enabling the fast construction of a series of C2,3- or C2,5-aminochalcogenated indole derivatives. Moreover, the application of this synthetic approach is demonstrated through the late-stage modification of pharmaceuticals and the derivatization of the products, highlighting its potential and significance. [ABSTRACT FROM AUTHOR]

Comprehensive Summary: A one‐pot synthesis of vicinal diamines using indoles, azoles and phenothiazines in a tandem multi‐component reaction is developed. The utilization of a copper‐iodine co‐catalytic system enables the generation of a diverse range of vicinal diaminoindoles with good selectivity and moderate to good yields. An attractive aspect of this method is that it can be conducted under mild and environmentally friendly conditions, showcasing its potential as an alternative approach for synthesizing vicinal diamines. Moreover, the use of a multicomponent tandem reaction highlights the power and versatility of such strategies in synthetic chemistry. [ABSTRACT FROM AUTHOR]

The development of a rational protocol to realize the complete regioselectivity and the capability to switch regioselectivity is an appealing yet challenging task. Herein, a regiodivergent C−H arylation of 2‐pyridylthiophenes has been demonstrated via the choice of RuII and PdII catalysts. The reactions proceeded smoothly in a good regioselective manner to afford the corresponding C3‐ and C5‐arylated thiophenes. Late‐stage diversification of biologically relevant scaffold derived from estrone and successful transformation of the products further highlighted the potential utility and importance of this synthetic strategy. [ABSTRACT FROM AUTHOR]

A novel and effective RhIII- and PdII-controlled switchable C–H alkenylation of 2-pyridylthiophenes with alkenes is realized. The alkenylation reactions proceeded smoothly in a highly regio- and stereo-selective manner to afford a broad range of C3- and C5-alkenylated products. Depending on the catalyst employed, the reactions involve two typical approaches: C3-alkenylation via chelation-assisted rhodation and C5-alkenylation via electrophilic palladation. This regiodivergent synthetic protocol was successfully applied for the straightforward building of π-conjugated difunctionalized 2-pyridylthiophenes, which may show great potential in organic electronic materials. [ABSTRACT FROM AUTHOR]

A novel europium complex with the mixed ligands of 1-methyl-3,5-bis(4′-carboxy-phenyl)-1,2,4-triazole (mbcpt) and p -phthalic acid (pa), [Eu 2 Cl 2 (H 3 O) 2 ( μ 4 -mbcpt) 2 ( μ 4 -pa)] n ( 1 ), has been synthesized under the solvothermal conditions and structurally characterized by single-crystal X-ray diffraction. Complex 1 exhibits a three-dimensional (3-D) metal-​organic framework. The 3-D open framework features a 2-fold-interpenetrated network. Solid-state diffuse reflectance spectroscopy uncovers the presence of a wide optical band gap of 3.56 eV, indicating that it is a wide band gap organic semiconductor material. Solid-state photoluminescence measurement reveals that complex 1 shows red light emission bands locating at 602, 611, 642 and 690 nm, which can be assigned to the 5 D 0 → 7 F J (Eu 3+ ) with the value of J = 1, 2, 3 and 4, respectively. Magnetic measurements reveal that complex 1 shows an antiferromagnetic behavior. [ABSTRACT FROM AUTHOR]

Introduction: Rocuronium intravenous pain is common in induction of general anesthesia. The aim of our study was to determine the median effective dose (ED50) of prophylactic intravenous remifentanil for the prevention of rocuronium injection pain and to explore the effect of age on the ED50. Methods: Eighty-nine adult patients undergoing elective general anesthesia, ASA I or II, regardless of gender or weight, were stratified according to age: group R1 18–44 years, group R2 45–59 years, and group R3 60–80 years. The initial dose of prophylactic remifentanil before rocuronium injection was set at 1 μg/kg lean body weight (LBW). The remifentanil doses were adjusted according to the degree of injection pain using the Dixon sequential method, with a ratio of 1.1 between adjacent doses. Injection pain was graded, and the occurrence of injection pain and adverse reactions were recorded. The ED50 and 95% confidence intervals (CIs) of remifentanil were calculated using the Dixon–Massey formula. Patients were asked whether they recalled feeling any injection pain in the post-anesthesia care unit (PACU). Results: The ED50 (95% CIs) of prophylactic remifentanil for the prevention of rocuronium injection pain were 1.266 μg/kg (1.186–1.351 μg/kg), 1.188 μg/kg (1.065–1.324 μg/kg), and 1.070 μg/kg (1.014–1.129 μg/kg) LBW in group R1, group R2, and group R3, respectively. No adverse reactions to remifentanil occurred in any group. In PACU, 84.6, 86.7, and 85.7% of patients who experienced injection pain had memories of the pain in group R1, group R2, and group R3, respectively. Conclusions: Prophylactic intravenous remifentanil can prevent rocuronium injection pain, and its ED50 decreases with age, with 1.266 μg/kg (18–44 years), 1.188 μg/kg (45–59 years), and 1.070 μg/kg LBW (60–80 years), respectively. Trial Registration: ClinicalTrials.gov: NCT05217238 (registration date 18 Dec 2021). [ABSTRACT FROM AUTHOR]

The position‐selective functionalization of the poorly reactive benzenoid nucleus of indoles has remained a great challenge in organic chemistry. Here we describe a directing‐group‐free, three‐component tandem C3‐acylation/C5,6‐H disulfenylation of indoles via an iodine‐, Lewis acid‐ and Brønsted acid‐cooperated mediated strategy. This protocol is remarkable for its exceptional regio‐ and chemo‐selectivity, broad substrate scope, good functional group tolerance and mild reaction conditions. Advantageously, the present protocol offers great potential for the development of general site‐selective functionalization at the benzenoid nucleus of indoles, removing the requirement for neighbouring activating groups. [ABSTRACT FROM AUTHOR]

A very easy sequential metathesis for the synthesis of Pd(II)–CMC@Ce(OH) 4 organic/inorganic hybrid and its application as effective pre-catalyst for the Suzuki–Miyaura reaction have been reported. It was found that the Pd nanoparticles (Pd NPs) were formed in situ in the course of the Suzuki–Miyaura couplings when Pd(II)–CMC@Ce(OH) 4 was used as a pre-catalyst. The activity of the Pd NPs in the reaction was enhanced synergistically by the unique redox properties (Ce 3+ /Ce 4+ ) of Ce(OH) 4 and coordination with carboxyl groups as well as free hydroxyl groups of the hybrid of CMC@Ce(OH) 4 . The results exhibit the Pd(0)–CMC@Ce(OH) 4 is super over Pd(II)@CMC, Pd(II)@CeO 2 , and Pd(II)@Ce(OH) 4 catalysts in the Suzuki–Miyaura reaction. Moreover, the catalyst could be easily separated by simple filtration and reused at least seven runs without losing its activity. [ABSTRACT FROM AUTHOR]

The first Trypsin from porcine pancreas catalyzed a novel one-pot three-component reaction of α-bromoketone, primary alkylamines, and phenylisothiocyanate for the synthesis of thiazole-imine derivatives with high yields (up to 98%) in a short time under mild conditions. The results revealed that Trypsin exhibited excellent catalytic activity and great tolerance for broad substrates. This Trypsin -catalyzed three component convergent method provides a novel strategy for the synthesis of thiazole-2-imine derivatives and expands the promiscuous functions of enzymes in organic synthesis. [ABSTRACT FROM AUTHOR]

• Based on the 0-1 integer programming, a new subspace clustering method is proposed, named k -sparse LSR. • The new method can directly solve the optimization of the LSR constrained by an L0-norm-based inequality without any relaxation. • With the help of the 0-1 integer constraint, the L0-norm-based constraint is equivalent to an intersection of two continuous constraint sets. • The new method is proven to have both k-sparsity and the grouping effect. Subspace clustering is a powerful technology for clustering high-dimensional data. Least squares regression (LSR) is one of the classical subspace clustering models because of the explicit solution and grouping effect that tends to cluster highly correlated data together. However, LSR lacks sparsity, which may lead to its sensitivity to noise and dimension of data. Since the ℓ 0 -norm constrained optimization is difficult to solve, we introduce a new method based on the 0-1 integer programming, named k -sparse LSR (KSLSR), to directly solve the optimization of the LSR constrained by an ℓ 0 -norm-based constraint without any relaxation, where k represents the maximum number of non-zero elements of the representation coefficient. With the help of the 0-1 integer constraint, the ℓ 0 -norm-based constraint is equivalent to two continuous constraints. Thus, the obtained KSLSR method with two continuous constraints is equivalent to the ℓ 0 -norm constrained optimization and can be effectively solved by the alternating direction multiplier method (ADMM). In addition, the new method is proven to provide a solution with both k -sparsity and the grouping effect, which makes it robust to the noise and dimension of data. Extensive experiments are conducted to demonstrate the effectiveness and superiority of the proposed method. [ABSTRACT FROM AUTHOR]

Background: Dexmedetomidine has controversial influence on cardiac electrophysiology. The aim of this study was to explore the effects of dexmedetomidine on perioperative cardiac electrophysiology in patients undergoing general anesthesia. Methods: Eighty-one patients were randomly divided into four groups: groups D1, D2, D3 receiving dexmedetomidine 1, 1, 0.5 μg/kg over 10 min and 1, 0.5, 0.5 μg/kg/h continuous infusion respectively, and control group (group C) receiving normal saline. Twelve-lead electrocardiograms were recorded at the time before dexmedetomidine/normal saline infusion (T1), loading dose finish (T2), surgery ending (T6), 1 h (T7) after entering PACU, 24 h (T8), 48 h (T9), 72 h (T10) and 1 month (T11) postoperatively. Cardiac circulation efficiency (CCE) were also recorded. Results: Compared with group C, QTc were significantly increased at T2 in groups D1 and D2 while decreased at T7 and T8 in group D3 (P < 0.05), iCEB were decreased at T8 (P < 0.05). Compared with group D1, QTc at T2, T6, T7, T9 and T10 and iCEB at T8 were decreased, and CCE at T2-T4 were increased in group D3 significantly (P < 0.05). Compared with group D2, QTc at T2 and iCEB at T8 were decreased and CCE at T2 and T3 were increased in group D3 significantly (P < 0.05). Conclusions: Dexmedetomidine at a loading dose of 0.5 μg/kg and a maintenance dose of 0.5 μg/kg/h can maintain stability of cardiac electrophysiology during perioperative period and has no significant adverse effects on CCE. Trial registration: ClinicalTrials.gov NCT04577430 (Date of registration: 06/10/2020). [ABSTRACT FROM AUTHOR]

Sterile filtration is an effective method to remove any microorganisms present during nanoemulsion preparation. However, it lacks effective control parameters. Here, we established a simple and rapid approach for the process control of nanoemulsion sterile filtration by utilizing optical density detection as a process control parameter. During sterile filtration, the optical density or optical density ratio of the filtrate were continuously monitored to explore the correlation between optical density and the emulsion content and the change in the optical density ratio before and after sterile filtration. In the emulsion stability test, the optical density ratio was determined. A good correlation was obtained between the optical density and the nanoemulsion content during sterile filtration, thereby reducing sterile filtration loss. The optical density ratio changed significantly after sterile filtration, indicating that it could be used as a process control parameter to monitor leakage during emulsion sterile filtration. The optical density ratio can be a characterization index for stability monitoring as it is more sensitive than particle size detection and more convenient than large particle detection. These parameters may be used for sterile filtration process control and as an index for nanoemulsion characterization. This approach overcomes the limitations of existing nanoemulsion characterization methods. [ABSTRACT FROM AUTHOR]

Surgical resection, the mainstay for melanoma treatment, faces challenges due to high tumor recurrence rates and complex postoperative wound healing. Chronic inflammation from residual disease and the risk of secondary infections impede healing. We introduce an innovative, injectable hydrogel system that integrates a multifaceted therapeutic approach. The hydrogel, crosslinked by calcium ions with sodium alginate, encapsulates a blood clot rich in dendritic cells (DCs) chemoattractants and melanoma cell-derived nanovesicles (NVs), functioning as a potent immunostimulant. This in situ recruitment strategy overcomes the limitations of subcutaneous tumor vaccine injections and more effectively achieves antitumor immunity. Additionally, the hydrogel incorporates Chlorella extracts, enhancing its antimicrobial properties to prevent wound infections and promote healing. One of the key findings of our research is the dual functionality of Chlorella extracts; they not only expedite the healing process of infected wounds but also increase the hydrogel's ability to stimulate an antitumor immune response. Given the patient-specific nature of the blood clot and NVs, our hydrogel system offers customizable solutions for individual postoperative requirements. This personalized approach is highlighted by our study, which demonstrates the synergistic impact of the composite hydrogel on preventing melanoma recurrence and hastening wound healing, potentially transforming postsurgical melanoma management. [ABSTRACT FROM AUTHOR]

Efficient cytosolic delivery is a significant hurdle when using short interfering RNA (siRNA) in therapeutic applications. Here we show that cholesterol-rich exosomes are prone to entering cancer cells through membrane fusion, achieving direct cytosolic delivery of siRNA. Molecular dynamics simulations suggest that deformation and increased contact with the target cell membrane facilitate membrane fusion. In vitro we show that cholesterol-enriched milk-derived exosomes (MEs) achieve a significantly higher gene silencing effect of siRNA, inducing superior cancer cell apoptosis compared with the native and cholesterol-depleted MEs, as well as conventional transfection agents. When administered orally or intravenously to mice bearing orthotopic or subcutaneous tumours, the cholesterol-enriched MEs/siRNA exhibit antitumour activity superior to that of lipid nanoparticles. Collectively, by modulating the cholesterol content of exosome membranes to facilitate cell entry via membrane fusion, we provide a promising approach for siRNA-based gene therapy, paving the way for effective, safe and simple gene therapy strategies., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

A one-pot strategy for iron-catalyzed C2,3-H arylphosphorylation of electron-deficient quinoxalines with phosphines and aryl compounds is reported. The proposed method features the use of non-noble metal catalysts, the capacity of utilizing multiple aryl compounds as substrates, the simultaneous formation of C-P and C-C bonds in one pot, the simplicity of its operation, the mildness of the reaction conditions, and its compatibility with a wide range of substrates. Moreover, it offers a practical route for direct access to 2-aryl-3-phosphino N -heteroarenes, a class of potential cyclometalated C^N and N^P bidentate ligands that are difficult to prepare with existing C(sp 2 )-H functionalization methods.

We have disclosed silver(I)-induced switching of regioselectivity in rhodium-catalyzed C-H alkynylation of indole derivatives with the help of a pivaloyl directing group by tuning C-H metalation modes. The judicious choice of AgOAc, Ag 2 O, and Ag 2 CO 3 affords an array of C2-alkynylated indoles, C4-alkynylated indoles, and C2,C4-dialkynylated indoles, respectively. The synthetic utility of the alkyne fragment is demonstrated by derivatization into valuable indole-based compounds.

The prospect of employing chemoimmunotherapy targeted towards the endoplasmic reticulum (ER) presents an opportunity to amplify the synergistic effects of chemotherapy and immunotherapy. In this study, we initially validated celastrol (CEL) as an inducer of immunogenic cell death (ICD) by promoting ER stress and autophagy in colorectal cancer (CRC) cells. Subsequently, an ER-targeted strategy was posited, involving the codelivery of CEL with PD-L1 small interfering RNAs (siRNA) using KDEL peptide-modified exosomes derived from milk (KME), to enhance chemoimmunotherapy outcomes. Our findings demonstrate the efficient transportation of KME to the ER via the Golgi-to-ER pathway. Compared to their non-targeting counterparts, KME exhibited a significant augmentation of the CEL-induced ICD effect. Additionally, it facilitated the release of danger signaling molecules (DAMPs), thereby stimulating the antigen-presenting function of dendritic cells and promoting the infiltration of T cells into the tumor. Concurrently, the ER-targeted delivery of PD-L1 siRNA resulted in the downregulation of both intracellular and membrane PD-L1 protein expression, consequently fostering the proliferation and activity of CD8 + T cells. Ultimately, the ER-targeted formulation exhibited enhanced anti-tumor efficacy and provoked anti-tumor immune responses against orthotopic colorectal tumors in vivo . Collectively, a robust ER-targeted delivery strategy provides an encouraging approach for achieving potent cancer chemoimmunotherapy., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Authors.)

The exploration of remote functionalization of indoles is impeded by the inherently dominant reactivity intrinsic to the pyrrole moiety. Herein, we delineate a novel strategy facilitated by Lewis acid mediation, enabling the remote C-H functionalization, which culminates in the synthesis of an array of selectively functionalized indole derivatives, encompassing 3-trifluoroacetyl and 5-benzoyl motifs, utilizing trifluoroacetic anhydride and various acyl chlorides. Notably, the protocol exhibits versatility, as epitomized by the extension of C5-acylation to alkylation and sulfonation reactions. This methodology is distinguished by its exemplary regio- and chemo-selectivity, extensive substrate scope, commendable tolerance to a diverse array of functional groups, and the employment of comparatively mild reaction conditions.

Two complementary regiodivergent C-H alkynylations of 2-arylthiazoles are reported. When Ru II catalysis is employed, an aryl ortho -alkynylation process is favored. The alkynylated products are gained in good yields. With the use of Pd II catalysis, a thiazole C5-alkynylation process is developed, allowing for the construction of C5-alkynylated products. This strategy not only expands the methods for the functionalization of 2-arylthiazoles, but also provides new opportunities for the rapid assembly of complex molecular structures, which may have great potential in organic synthesis, medicinal chemistry, and materials science.

Foam flooding is an important tool for reservoir development. This study aims to further investigate the interaction between stimulus-responsive wormlike micelle (WLM)-CO 2 foams and crude oil. We performed micromorphology experiments as our major studies and used molecular dynamics simulations as an auxiliary tool for interfacial analysis. We utilized foam generation, liquid separation, and defoaming as the entry points of experimental research and energy as the quantitative assessment index to investigate the dynamic process of the action of different oil contents and oil phase types in a DOAPA@NaSal-H + foam system. We also examined the role of NaSal in the generation and development of the foam system. Results indicated that the law of crude oil's effect on foam could be summarized as "low contents are beneficial and high contents are harmful." In addition, although the DOAPA@NaSal-H + foam system has high compatibility for saturated and aromatic hydrocarbons, it is highly suitable for application in reservoir environments with relatively high asphaltene and resin contents. Through combined experimental and simulation approaches, we clarified the law governing the stability of the DOAPA@NaSal-H + foam system in different oil-containing environments, identified the key role of NaSal, and provided a reference for the targeted application of the DOAPA@NaSal-H + foam system in different oil reservoirs.

Elevated interstitial fluid pressure (IFP) within pathological tissues (e.g., tumors, obstructed kidneys, and cirrhotic livers) creates a significant hindrance to the transport of nanomedicine, ultimately impairing the therapeutic efficiency. Among these tissues, solid tumors present the most challenging scenario. While several strategies through reducing tumor IFP have been devised to enhance nanoparticle delivery, few approaches focus on modulating the intrinsic properties of nanoparticles to effectively counteract IFP during extravasation and penetration, which are precisely the stages obstructed by elevated IFP. Herein, we propose an innovative solution by engineering nanoparticles with a fusiform shape of high curvature, enabling efficient surmounting of IFP barriers during extravasation and penetration within tumor tissues. Through experimental and theoretical analyses, we demonstrate that the elongated nanoparticles with the highest mean curvature outperform spherical and rod-shaped counterparts against elevated IFP, leading to superior intratumoral accumulation and antitumor efficacy. Super-resolution microscopy and molecular dynamics simulations uncover the underlying mechanisms in which the high curvature contributes to diminished drag force in surmounting high-pressure differentials during extravasation. Simultaneously, the facilitated rotational movement augments the hopping frequency during penetration. This study effectively addresses the limitations posed by high-pressure impediments, uncovers the mutual interactions between the physical properties of NPs and their environment, and presents a promising avenue for advancing cancer treatment through nanomedicine., Competing Interests: Competing interests statement:The authors declare no competing interest.

An organoselenium-catalyzed C2,3-diarylation of unprotected N-H indoles with electron-rich aromatics has been developed. This one-pot multicomponent tandem cross-dehydrogenation coupling reaction allows for the incorporation of two different aromatic groups to indoles. More importantly, this approach offers significant advantages, including a high atom and step economy, eliminating the need for prepreparation of the reaction substrates, streamlining the synthetic process and enhancing its practicality. Overall, this organoselenium-catalyzed C2,3-diarylation reaction presents an efficient and versatile strategy for the functionalization of indole derivatives.

Lung cancer is the leading cause of cancer death, and its effective treatment is a difficult medical problem. Lung cancer belongs to the traditional Chinese medicine(TCM) disease categories of lung accumulation, lung amassment, and overstrain cough. Rich theoretical basis and practical experience have been accumulated in the TCM treatment of lung cancer. Astragali Radix is one of the representatives of Qi-tonifying drugs. It mainly treat the lung cancer with the syndrome of Qi deficiency and pathogen stagnation, following the principle of reinforcing healthy Qi and eliminating patgogenic Qi. Astragali Radix exerts a variety of pharmacological activities in the treatment of lung cancer, including inhibiting tumor cell proliferation and promoting tumor cell apoptosis, inhibiting tumor invasion and migration, regulating the tumor microenvironment, suppressing tumor angiogenesis, modulating autophagy, inducing macrophage polarization, enhancing immunity, inhibiting immune escape, and reversing cisplatin resistance. The active ingredients of Astragali Radix in treating lung cancer include polysaccharides, saponins, and flavonoids. This study reviewed the pharmacological activities and active ingredients of Astragali Radix in the treatment of lung cancer, providing a basis for the development and utilization of Astragali Radix resources and active ingredients and the research and development of anti-tumor drugs.

A metal-free one-pot oxidative cross-dehydrogenation coupling reaction for the formation of C-N/C-C bonds at the C2,3-positions of indoles with azoles and quinoxalinones has been developed. The proposed method has several notable features, including metal-free catalysis, the use of N-H free indoles as substrates, ease of operation, mild reaction conditions, and compatibility with a wide range of substrates.

Background: The aim of this paper was to explore pupillary monitoring for determining remifentanil consumption during general anesthesia and evaluating postoperative recovery quality., Methods: Eighty patients undergoing elective laparoscopic uterine surgery were randomly divided into pupillary monitoring group (Group P) and control group (Group C). In Group P, remifentanil dosage during general anesthesia was determined according to pupil dilation reflex; in Group C, it was adjusted according to hemodynamic changes. Intraoperative remifentanil consumption and endotracheal tube extraction time were recorded. The Numerical Rating Scale (NRS) Score, hemodynamic changes, and opioid-related adverse reactions in the post-anesthesia care unit were also recorded. The parameters of pupil light reflex from extubation to 30 min after extubation were analyzed in Group P, and the responsiveness of these parameters and hemodynamic changes to NRS was determined by ROC curve analyses., Results: Compared with Group C, in Group P, intraoperative remifentanil consumption, the NRS Score at 20 minutes after extubation, extubation time, and the incidence of nausea, vomiting, and respiratory amnesia were all significantly decreased (all, P<0.05). In Group P, ∆HR and ∆MAP had no value in judging the change of NRS. The ROC values and diagnostic cutoff values of ΔInit, ΔACV, and ΔMCV responding to NRS variation were 0.775 (95% CI: 0.582-0.968), 0.734(95% CI: 0.537-0.930), and 0.822 (95% CI: 0.648-0.997) and 0.21 (sensitivity, 92.3%; specificity, 23.1%), -1.3 (sensitivity, 92.3%; specificity, 18.3%), and -1.0 (sensitivity, 84.6%; specificity, 17.7%), respectively., Conclusions: Intraoperative pupil dilation reflex monitoring can reduce remifentanil consumption and improve postoperative recovery quality. Furthermore, postoperative pupil light reflex monitoring can help evaluate pain degree with high sensitivity.

The clinical utility of gemcitabine, an antimetabolite antineoplastic agent applied in various chemotherapy treatments, is limited due to the required intravenous injection. Although chemical structure modifications of gemcitabine result in enhanced oral bioavailability, these modifications compromise complex synthetic routes and cause unexpected side effects. In this study, gemcitabine-loaded glycocholic acid-modified micelles (Gem-PPG) were prepared for enhanced oral chemotherapy. The in vitro transport pathway experiments revealed that intact Gem-PPG were transported across the intestinal epithelial monolayer via an apical sodium-dependent bile acid transporter (ASBT)-mediated pathway. In mice, the pharmacokinetic analyses demonstrated that the oral bioavailability of Gem-PPG approached 81%, compared to less than 20% for unmodified micelles. In addition, the antitumor activity of oral Gem-PPG (30 mg/kg, BIW) was superior to that of free drug injection (60 mg/kg, BIW) in the xenograft model. Moreover, the assessments of hematology, blood chemistry, and histology all indicated the hypotoxicity profile of the drug-loaded micelles.

Study Objectives: We explored the effects of stellate ganglion block on postoperative sleep disturbance in patients scheduled to undergo radical surgery for gastrointestinal malignancies., Methods: Forty such patients were randomly assigned to the control group (Group C) or the preoperative stellate ganglion block treatment group (Group S). Using actigraphy, sleep quality was evaluated on the first night before the operation and first, second, and third postoperative nights. The Pittsburgh Sleep Quality Index scale was used for sleep state assessment on 1 day preoperatively and the first, second, third, fifth, and seventh days postoperatively. Plasma interleukin (IL)-1, IL-6, and IL-10 and melatonin levels were checked at 1 day preoperatively and the first and third days postoperatively. Mean arterial pressure, heart rate, and pulse oxygen saturation (SpO 2 ) were recorded before general anesthesia induction, immediately after tracheal intubation, at the beginning of the operation, 1 and 2 hours after the beginning of the operation, at the end of the operation, immediately after extubation, and 30 minutes after transfer to the postanesthesia care unit., Results: Compared with Group C, in Group S sleep efficiency, total sleep time, and sleep maintenance were increased and sleep period change index, number of awakenings, wake after sleep onset, and body movements were reduced on the first and second postoperative nights; Pittsburgh Sleep Quality Index scores and occurrence of postoperative sleep disturbance were lower on the first and second nights postoperatively; IL-6 was reduced on the first night postoperatively; IL-1 and IL-10 were reduced on the third night postoperatively; melatonin was increased on the first night postoperatively; and mean arterial pressure and heart rate were decreased before general anesthesia induction, immediately after tracheal intubation, and at the end of the operation (all P < .05). Conclusions: Stellate ganglion block alleviates postoperative sleep disturbance by reducing postoperative inflammatory response, increasing melatonin levels, and stabilizing perioperative hemodynamics in patients undergoing radical surgery for gastrointestinal malignancies., Clinical Trial Registration: Registry: ClinicalTrials.gov; Name: The Effect of Stellate Ganglion Block on Postoperative Sleep Disturbance and Cognitive Function in Elderly Surgical Patients; URL: https://clinicaltrials.gov/ct2/show/NCT04800653; Identifier: NCT04800653., Citation: Yan S, Wang Y, Yu L, et al. Stellate ganglion block alleviates postoperative sleep disturbance in patients undergoing radical surgery for gastrointestinal malignancies. J Clin Sleep Med . 2023;19(9):1633-1642., (© 2023 American Academy of Sleep Medicine.)

Herein, a ruthenium-mediated remote C-H mono- and disulfonylation of 2-pyridones with arylsulfonyl chlorides is developed. The catalytic system consisting of a [Ru( p -cymene)Cl 2 ] 2 catalyst and KOAc additive allows 2-pyridones to undergo C3,C5-disulfonylation in 1,4-dioxane, and C5-sulfonylation when the C3-position of 2-pyridones is blocked. The successful transformation of the products and late-stage modification of estrone further highlighted the potential utility and significance of this synthetic protocol. Preliminary mechanistic studies indicated that the remote regioselectivity might be dictated via chelation-assisted ruthenation.