Asymmetric hydrogenation of ketimines with minimally different alkyl groups.

Asymmetric catalysis allows the synthesis of optically active compounds, often requiring the differentiation between two substituents on prochiral substrates1. Despite decades of development of mainly noble metal catalysts, achieving differentiation between substituents with similar steric and electronic properties remains a significant challenge2,3. Here, we introduce a class of earth-abundant manganese catalysts for the asymmetric hydrogenation of dialkyl ketimines to give a range of chiral amine products. These catalysts distinguish between pairs of minimally differentiated alkyl groups bound to the ketimine, such as methyl and ethyl, and even subtler distinctions, like ethyl and n-propyl. The degree of enantioselectivity can be adjusted by modifying the components of the chiral manganese catalyst. This reaction demonstrates a wide substrate scope and achieves a turnover number (TON) of up to 107,800. Our mechanistic studies indicate that the exceptional stereoselectivity arises from the modular assembly of confined chiral catalysts and cooperative non-covalent interactions between the catalyst and the substrate.

Enhancing Hydride Transfer in Catalytic Hydrogenation via σ-Electron-Induced Polarization of Imines.

In this study, we investigated the role of aluminum cations in facilitating hydride transfer during the hydrogenation of imines within the context of Noyori-type metal-ligand cooperative catalysis. We propose a novel model involving aluminum cations directly coordinated with imines to induce activation from the lone pair electron site, a phenomenon termed σ-induced activation. The aluminum metal-hydride amidate complex ("HMn-NAl") exhibits a higher ability of hydride transfer in the hydrogenation of imines compared to its lithium counterpart ("HMn-NLi"). Density functional theory (DFT) calculations uncover that the aluminum cation efficiently polarizes unsaturated bonds through σ-electron-induced activation in the transition state of hydride transfer, thereby enhancing substrate electrophilicity more efficiently. Additionally, upon substrate coordination, aluminum's coordination saturation improves the hydride nucleophilicity of the HMn-NAl complex via the breakage of the Al-H coordination bond.

The Long-Acting Serine Protease Inhibitor mPEG-SPA-MDSPI16 Alleviates LPS-Induced Acute Lung Injury.

Anti-inflammatory drugs have become the second-largest class of common drugs after anti-infective drugs in animal clinical care worldwide and are often combined with other drugs to treat fever and viral diseases caused by various factors. In our previous study, a novel serine protease inhibitor-encoding gene (MDSPI16) with improved anti-inflammatory activity was selected from a constructed suppressive subducted hybridization library of housefly larvae. This protein could easily induce an immune response in animals and had a short half-life, which limited its wide application in the clinic. Thus, in this study, mPEG-succinimidyl propionate (mPEG-SPA, Mw = 5 kDa) was used to molecularly modify the MDSPI16 protein, and the modified product mPEG-SPA-MDSPI16, which strongly inhibited elastase production, was purified. It had good stability and safety, low immunogenicity, and a long half-life, and the IC50 for elastase was 86 nM. mPEG-SPA-MDSPI16 effectively inhibited the expression of neutrophil elastase and decreased ROS levels. Moreover, mPEG-SPA-MDSPI16 exerted anti-inflammatory effects by inhibiting activation of the NF-κB signaling pathway and the MAPK signaling pathway in neutrophils. It also exerted therapeutic effects on a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. In summary, mPEG-SPA-MDSPI16 is a novel anti-inflammatory protein modified with PEG that has the advantages of safety, nontoxicity, improved stability, and strong anti-inflammatory activity in vivo and in vitro and is expected to become an effective anti-inflammatory drug.

Establishment of a risk classifier to predict the in-hospital death risk of nosocomial fungal infections in cancer patients.

BACKGROUND: Patients with malignancy are at a higher risk of developing nosocomial infections. However, limited studies investigated the clinical features and prognostic factors of nosocomial infections due to fungi in cancer patients. Herein, this study aims to investigate the clinical characteristics of in-hospital fungal infections and develop a nomogram to predict the risk of in-hospital death during fungal infection of hospitalized cancer patients. METHODS: This retrospective observational study enrolled cancer patients who experienced in-hospital fungal infections between September 2013 and September 2021. Univariate and multivariate logistic regression analyses were performed to identify independent predictors of in-hospital mortality. Variables demonstrating significant statistical differences in the multivariate analysis were utilized to construct a nomogram for personalized prediction of in-hospital death risk associated with nosocomial fungal infections. The predictive performance of the nomogram was evaluated using receiver operating characteristic (ROC) curves, calibration curves, and decision curve analysis. RESULTS: A total of 216 participants were included in the study, of which 57 experienced in-hospital death. C.albicans was identified as the most prevalent fungal species (68.0%). Respiratory infection accounted for the highest proportion of fungal infections (59.0%), followed by intra-abdominal infection (8.8%). The multivariate regression analysis revealed that Eastern Cooperative Oncology Group Performance Status (ECOG-PS) 3-4 (odds ratio [OR] = 6.08, 95% confidence interval [CI]: 2.04-18.12), pulmonary metastases (OR = 2.76, 95%CI: 1.11-6.85), thrombocytopenia (OR = 2.58, 95%CI: 1.21-5.47), hypoalbuminemia (OR = 2.44, 95%CI: 1.22-4.90), and mechanical ventilation (OR = 2.64, 95%CI: 1.03-6.73) were independent risk factors of in-hospital death. A nomogram based on the identified risk factors was developed to predict the individual probability of in-hospital mortality. The nomogram demonstrated satisfactory performance in terms of classification ability (area under the curve [AUC]: 0.759), calibration ability, and net clinical benefit. CONCLUSIONS: Fungi-related nosocomial infections are prevalent among cancer patients and are associated with poor prognosis. The constructed nomogram provides an invaluable tool for oncologists, enabling them to make timely and informed clinical decisions that offer substantial net clinical benefit to patients.

Au nanoclusters-decorated WO3 nanorods for ultrasensitive photoelectrochemical sensing of Hg2.

Photosensitizers and enzyme mimics are extensively used in photoelectrochemical (PEC) sensing, but few materials can be used as both photosensitizers and enzyme mimics in PEC sensing. Herein, we report Au nanoclusters (AuNCs) as both photosensitizers and peroxidase mimics for sensitive PEC sensing of Hg2+. It is found that AuNCs can act as photosensitizers to improve the PEC activity of WO3 nanorods; so the WO3/AuNCs composite material can be used as an advanced photosensitive material for PEC detection. AuNCs can also catalyze precipitate formation on the photoelectrode because of their peroxidase mimetic activity, and the interface electron transfer is hindered by the formed precipitate. Thus, the photocurrent of the WO3/AuNCs-based photoelectrode is quenched. When Hg2+ is present, the AuNCs-catalyzed precipitate formation is inhibited by Hg2+ because of the binding of Hg2+ to AuNCs through Hg2+-Au+ interactions. The photocurrent of the WO3/AuNCs-based photoelectrode increases accordingly, enabling "signal on" PEC detection of Hg2+. A broad linear range for Hg2+ detection is achieved between 1.0 pM and 50 nM with a detection limit of 0.2 pM. We have developed an advanced photosensitive material and introduced a simple method for PEC detection of Hg2+.

1T-MoS2 Nanosheets Coupled with CoS2 Nanoparticles: Electronic Modulation for Efficient Electrochemical Nitrogen Fixation.

Electrocatalytic nitrogen reduction reaction (eNRR), a substitute process for the conventional Haber-Bosch for NH3 production, has drawn tremendous attention due to its merits in mild conditions, abundant reactant sources, low energy consumption, and environmental protection. However, electrocatalysts for eNRR are still subjected to low catalytic activity and selectivity. Herein, we constructed a CoS2/1T-MoS2 heterostructure with CoS2 nanoparticles uniformly loaded on 1T-MoS2 nanosheets and applied it as an eNRR electrocatalyst for the first time. Theoretical calculation suggests that electron transfer from CoS2 to 1T-MoS2 across their contact interface optimizes the local electronic structure of 1T-MoS2, where the electron-depletion region near CoS2 is in favor of accepting lone-pair electrons from N2 to enable N2 absorption, and the electron-accumulation region near 1T-MoS2 is conductive to break inert N≡N triple bonds. Unlike pure 1T-MoS2, the potential-determining step (PDS) demonstrates a significantly lower energy barrier. In addition, the weak interaction between CoS2/1T-MoS2 and hydrogen discourages competitive hydrogen evolution reaction. As a result, CoS2/1T-MoS2 exhibited noticeably improved eNRR activity and selectivity, with an NH3 yield of 59.3 µg h-1 mg-1 and a high Faradaic efficiency of 26.6%.

Cobalt-Catalyzed Desymmetric Isomerization of Exocyclic Olefins.

Chiral cyclic olefins, 1-methylcyclohexenes, are versatile building blocks for the synthesis of pharmaceuticals and natural products. Despite the prevalence of these structural motifs, the development of efficient synthetic methods remains an unmet challenge. Herein we report a novel desymmetric isomerization of exocyclic olefins using a series of newly designed chiral cobalt catalysts, which enables a straightforward construction of chiral 1-methylcyclohexenes with diversified functionalities. The synthetic utility of this methodology is highlighted by a concise and enantioselective synthesis of a natural product, ß-bisabolene. The versatility of the reaction products is further demonstrated by multifarious derivatizations.

Construction and Validation of a Novel Nomogram to Predict the Overall Survival of Patients With Combined Small Cell Lung Cancer: A Surveillance, Epidemiology, and End Results Population-Based Study.

INTRODUCTION: Combined small cell lung cancer (C-SCLC) represents a rare subtype of all small cell lung cancer cases, with limited studies investigated its prognostic factors. The aim of this study was to construct a novel nomogram to predict the overall survival (OS) of patients with C-SCLC. METHODS: In this retrospective study, a total of 588 C-SCLC patients were selected from the Surveillance, Epidemiology, and End Results database. The univariate and multivariate Cox analyses were performed to identify optimal prognostic variables and construct the nomogram, with concordance index (C-index), receiver operating characteristic curves, and calibration curves being used to evaluate its discrimination and calibration abilities. Furthermore, decision curve analysis (DCA), integrated discrimination improvement (IDI), and net reclassification index (NRI) were also adopted to assess its clinical utility and predictive ability compared with the classic TNM staging system. RESULTS: Seven independent predictive factors were identified to construct the nomogram, including T stage, N stage, M stage, brain metastasis, liver metastasis, surgery, and chemotherapy. We observed a higher C-index in both the training (.751) and validation cohorts (.736). The nomogram has higher area under the curve in predicting 6-, 12-, 18-, 24-, and 36-month survival probability of patients with C-SCLC. Meanwhile, the calibration curves also revealed high consistencies between the actual and predicted OS. DCA revealed that the nomogram could provide greater clinical net benefits to these patients. We found that the NRI for 6- and 12-month OS were .196 and .225, and the IDI for 6- and 12-month OS were .217 and .156 in the training group, suggesting that the nomogram can predict a more accurate survival probability. Similar results were also observed in the validation cohort. CONCLUSION: We developed and verified a novel nomogram that can help clinicians recognize high-risk patients with C-SCLC and predict their OS.

Recipient vessel selection for multiple free flap transfers in head and neck reconstruction at different periods.

BACKGROUND: Treatment decisions can be challenging in patients undergoing multiple oropharyngeal microsurgical reconstructions at different periods by various causes. We, retrospectively, reviewed patients with at least three consecutive free flap reconstructions to determine the optimal strategy for selecting recipient vessels. METHODS: Then, 36 patients (33 men and 3 women) who underwent at least 3 microsurgical reconstructions with a total of 51 free flap transfers for head and neck defects were included in this report. The most common reason for multiple microsurgical reconstructions was recurrent disease. For reconstructions, recipient vessel candidates on the same side of the head and neck were prioritized; if ipsilateral vessels were unavailable, contralateral recipient vessels, which might necessitate vein grafts, were used. RESULTS: The most common reconstructions were anterolateral thigh flaps (19 cases). The most commonly used contralateral recipient vessels were the superior thyroid artery, facial artery, and external jugular vein. All vessel anastomoses were performed using the end-to-end method. Postoperative complications occurred at the sites of 26 free flap reconstructions. The overall flap reconstruction success rate in patients with at least three surgeries was 90.2%. The median follow-up duration was 25.8 months. During follow-up, 26 patients survived until the end of follow-up. CONCLUSIONS: In patients undergoing multiple free flap reconstructions, recipient vessels on the ipsilateral side that have not been subjected to radiation should be selected first. Recipient vessels contralateral to the reconstruction side can then be selected; however, they may require vein grafts. Finally, distant healthy recipient vessels can be selected through vein grafting.

Manganese-Catalyzed Asymmetric Hydrogenation of Quinolines Enabled by π-π Interaction*.

The non-noble metal-catalyzed asymmetric hydrogenation of N-heteroaromatics, quinolines, is reported. A new chiral pincer manganese catalyst showed outstanding catalytic activity in the asymmetric hydrogenation of quinolines, affording high yields and enantioselectivities (up to 97 % ee). A turnover number of 3840 was reached at a low catalyst loading (S/C=4000), which is competitive with the activity of most effective noble metal catalysts for this reaction. The precise regulation of the enantioselectivity were ensured by a π-π interaction.

C(sp3)-CF3 Reductive Elimination from a Five-Coordinate Neutral Copper(III) Complex.

The reductive elimination from a high-valent late-transition-metal complex for the formation of a carbon-carbon or carbon-heteroatom bond represents a fundamental product-forming step in a number of catalytic processes. While reductive eliminations from well-defined Pt(IV), Pd(IV), Ni(III)/Ni(IV), and Au(III) complexes have been studied, the analogous reactions from neutral Cu(III) complexes remain largely unexplored. Herein, we report the isolation of a stable, five-coordinate, neutral square pyramidal Cu(III) complex that gives CH3-CF3 in quantitative yield via reductive elimination. Mechanistic studies suggest that the reaction occurs through a synchronous bond-breaking/bond-forming process via a three-membered ring transition state.

Long-term outcomes of trans-oral robotic surgery-assisted total laryngectomy for recurrent laryngeal cancers.

OBJECTIVE: For recurrent laryngeal cancers, trans-oral robotic surgery has been used to perform total laryngectomy, but limited cases had been reported without long-term outcome follow-up. This study aims at presenting the largest longitudinal retrospective cohort in a single tertiary referral medical center. METHODS: From November 2013 to August 2017, seven patients with recurrent laryngeal cancers without evidence of neck metastasis were selected to receive trans-oral robotic surgery-assisted TL without neck dissection. The para-operative details including the surgical success rates, surgical methods, resection extent, drainage tube placement, pharyngeal wound closure, console surgical time, pathologic findings and long-term complications were reviewed and described. The study end points include survival rates and preservation of swallowing function without tube feeding. RESULTS: Trans-oral robotic surgery-assisted total laryngectomy was successfully performed on all seven patients with mean surgical console time of 111 ± 66 min. Strap muscles and hyoid bone were resected like open surgery in six and five patients, respectively. For all the seven patients, there was no severe pharyngo-cutaneous fistula formation requiring repair in a second surgery, but tracheostoma stenosis was not uncommon (57%). Three patients received adjuvant chemotherapy/radiotherapy. After follow-up of 36.1 ± 15.8 months, two patients had neck recurrence, and one patient died 19 months after surgery, but the other five patients were alive without disease recurrence. The overall survival rate was 85.7% (6/7), and all patients had good swallowing function without tube feeding. CONCLUSIONS: Trans-oral robotic surgery-assisted total laryngectomy is a feasible approach for selected patients with recurrent laryngeal cancers. The oncologic and functional outcomes were satisfactory. Further larger cohort study is worthwhile to further elucidate the value of trans-oral robotic surgery-assisted total laryngectomy.

Robot-assisted microvascular anastomosis in head and neck free flap reconstruction: Preliminary experiences and results.

BACKGROUND: The da Vinci Surgical System has facilitated considerable advancements in surgery. The process and results of robot-assisted microvascular anastomosis in real clinical situations have rarely been reported. This study presents our experience of performing robot-assisted microvascular anastomosis in free flap reconstruction in patients with oropharyngeal cancer. PATIENTS AND METHODS: This was a retrospective study of reconstructive operations using a free radial forearm flap for oropharyngeal defects after tumor extirpation in 15 consecutive adult patients (12 men and 3 women). In total, 17 robot-assisted microvascular vessel anastomoses (2 arteries and 15 veins) were performed; moreover, 13 arteries and 13 veins were anastomosed using the standard operating microscope and hand-sewing technique. RESULTS: The recipient and donor vessel diameters were 2.5 ± 0.7 and 2.1 ± 0.8 mm, respectively. The donor blood vessel diameter selected for anastomosis using da Vinci Surgical System was significantly smaller (2.1 ± 0.8 vs. 2.5 ± 0.6 mm) than that for a standard operating microscope and hand-sewing technique (p = .021), the operating time spent (38.4 ± 10.4 vs. 28.0 ± 7.7 min) was significantly longer (p < .001). The vascular patency rate was 100%, and all flaps survived without requiring additional operation for revision. CONCLUSION: Robotic surgical systems can facilitate vascular microanastomosis and provide a blood vessel patency rate comparable to that of a standard operating microscope and hand-sewing technique.

A Key Intermediate in Copper-Mediated Arene Trifluoromethylation, [nBu4 N][Cu(Ar)(CF3 )3 ]: Synthesis, Characterization, and C(sp2 )-CF3 Reductive Elimination.

The synthesis, characterization, and C(sp2 )-CF3 reductive elimination of stable aryl[tris(trifluoromethyl)]cuprate(III) complexes [nBu4 N][Cu(Ar)(CF3 )3 ] are described. Mechanistic investigations, including kinetic studies, studies of the effect of temperature, solvent, and the para substituent of the aryl group, as well as DFT calculations, suggest that the C(sp2 )-CF3 reductive elimination proceeds through a concerted carbon-carbon bond-forming pathway.

Impact of microsatellite alteration in surgical margins on local recurrence in oral cavity cancer patients.

The aim of this study was to investigate the association between microsatellite alteration in the surgical margins and local recurrence of oral cavity squamous cell carcinoma patients. Surgical specimens confirmed by pathological examination and corresponding surgical margins were collected from 120 oral cavity squamous cell carcinoma patients. Ten microsatellite markers were examined in the tumor specimens and paired surgical margins, which proved to be negative on pathological assessment. The specimens and surgical margins were amplified by polymerase chain reaction followed by computerized analysis. Forty-two specimens (35.0 %) with microsatellite instability (MSI) in at least one marker were found, and more than half of the specimens (n = 73, 60.8 %) had loss of heterozygosity (LOH) in at least one marker. Although MSI and LOH were not associated with the prognosis of oral cavity squamous cell carcinoma patients, presence of MSI in the tumor-free surgical margins increased the risk of local recurrence (hazard ratio: 9.549; 95 % confidence interval: 4.143-22.01). Genetic analysis of tumor-free surgical margins is a useful tool for identifying oral cavity squamous cell carcinoma patients who are vulnerable to local recurrence.

Functional Outcomes and Complications of Robot-Assisted Free Flap Oropharyngeal Reconstruction.

BACKGROUND: Robotic surgical systems provide a clear, magnified 3-dimensional visualization as well as precise, stable instrumental movement, thereby minimizing technical difficulties that may be encountered in the surgical treatment of oropharyngeal tumors. This study assessed the outcomes of robotic-assisted free flap oropharyngeal reconstruction compared with those of conventional free flap reconstruction. MATERIALS AND METHODS: A retrospective review of 47 patients who underwent reconstructive operations using a free radial forearm fasciocutaneous flap for oropharyngeal defects was conducted over a 20-month period (May 2013-December 2014). Complications were evaluated for a robot-assisted reconstruction group and a conventional reconstruction group; postoperative complication rates and revision rates were further evaluated. The Functional Intraoral Glasgow Scale (FIGS) was adopted for functional outcome assessment. RESULTS: This study recruited 47 people who underwent reconstructive operations using a free radial forearm fasciocutaneous flap for oropharyngeal defects (14 robot-assisted and 33 conventional reconstructions). The mean postoperative FIGS score was 10.29 ± 2.02 in the robot-assisted group (P = 0.010) and 8.42 ± 2.29 in the conventional group at 1 month postoperatively. The mean postoperative FIGS score was 12.57 ± 1.91 in the robot-assisted group (P = 0.005) and 9.91 ± 3.09 in the conventional group at 3 months postoperatively. Complication rates between the robot-assisted and conventional groups were similar for flap failure (P = 0.531), partial necrosis, wound infection, hematoma or seroma formation (P = 0.893), wound dehiscence, and fistula formation (P = 0.515). The number of flap revision operations requiring additional surgery (P = 0.627) was comparable between the cohorts. CONCLUSIONS: There is no significant difference in complications or revision rates between the robot-assisted and conventional oropharyngeal reconstructions. The functional postoperative outcomes of robot-assisted reconstructions are superior to those of conventional reconstructions. Robotic surgical systems provide a safe option with optimal postoperative oral function for the free flap reconstruction of oropharyngeal defects without lip or mandible splitting.

The impact of tissue glue in wound healing of head and neck patients undergoing neck dissection.

We investigated the impact of fibrin glue on postoperative drainage amount and duration in head and neck cancer patients who underwent neck dissection. This study was a prospective randomized controlled trial. Patients who were scheduled to undergo neck dissection due to head and neck cancer were eligible for this study. After receiving a detailed explanation, all patients signed an informed consent form before enrollment. Patients were then randomly assigned to the study group (fibrin glue) or control group. In the study group, 2 ml of fibrin glue (Tissucol(®); Duploject, Baxter AG) was applied on the surface of the surgical wound before closure. Basic demographic data along with tumor-related features, operation-related variables, postoperative drainage amount/duration, postoperative pain, and analgesic usage were collected and analyzed. A total of 15 patients were included in the final analyses, with eight patients in the study group and seven patients in the control group. No significant differences were found between the two groups in age, gender, primary site, clinical N stage, neck dissection levels, perioperative bleeding, postoperative drainage amount/duration, hospitalization duration, and postoperative pain status. The application of 2 ml fibrin glue by the method described herein did not reduce the postoperative drainage amount/duration nor the postoperative pain status in patients who underwent neck dissection.

Expression of magnesium transporter genes in head and neck cancer patients underwent neoadjuvant cisplatin-based chemotherapy.

We aimed to investigate expression of magnesium transporter genes in patients with head and neck cancer who underwent cisplatin-based neoadjuvant chemotherapy and their association with serum magnesium level. Head and neck cancer patients scheduled to undergo neoadjuvant cisplatin-based chemotherapy were eligible for enrollment. Blood samples were obtained at three time points: prior to, during, and after completion of chemotherapy. Expression levels of magnesium transporter genes were determined by quantitative real-time PCR. A total of 23 patients were included in the final analysis. The average serum magnesium levels dropped 6.98 and 5.20% during and after completion of chemotherapy. There were neither significant associations between serum magnesium level and demographic variables nor tumor-related variables. SLC41A1 expression level was positively correlated with serum magnesium whereas TRPM6 expression level was negatively correlated with serum magnesium. Serum magnesium level decreased during cisplatin-based chemotherapy in head and neck cancer patients. Further studies are warranted to investigate optimal magnesium measurement and substitution protocol.

Risk factors of recipient site infection in head and neck cancer patients undergoing pectoralis major myocutaneous flap reconstruction.

The aim of this study was to investigate the factors associated with infection at the recipient site of pectoralis major myocutaneous flap (PMMF) of head and neck cancer patients. We retrospectively reviewed head and neck cancer patients who underwent PMMF reconstruction and identified those with recipient site infection. Variables of patients with and without infection were compared and associated factors were investigated by logistic regression model. A total of 478 patients were included in the final analysis and 183 patients (38.3%) developed recipient site infection. Lower margin of skin island, concurrent tracheotomy, diabetes mellitus, mandibular plate reconstruction, prior radiation, and peri-operative blood transfusion were independent factors associated with recipient site infection of PMMF. Skin island of PMMF beyond the eighth intercostal space markedly increased the risk of recipient site infection after major head and neck cancer surgery. Recognition of relevant factors associated with infection may help surgeons to identify those at risk.