Zirconium-hydride-catalyzed site-selective hydroboration of amides for the synthesis of amines:Mechanism,scope,and application

Developing mild and efficient catalytic methods for the selective synthesis of amines is a longstanding research objective.In this respect,catalytic deoxygenative amide reduction has proven to be promising but challenging,as this approach necessitates selective C-O bond cleavage.Herein,we report the selective hydroboration of primary,secondary,and tertiary amides at room temperature catalyzed by an earth-abundant-metal catalyst,Zr-H,for accessing diverse amines.Various readily reducible functional groups,such as esters,alkynes,and alkenes,were well tolerated.Furthermore,the methodology was extended to the synthesis of bio-and drug-derived amines.Detailed mechanistic studies revealed a reaction pathway entailing aldehyde and amido complex formation via an unusual C-N bond cleavage-reformation process,followed by C-O bond cleavage.

Machine learning enabling prediction in mechanical performance of Ti6Al4V fabricated by large-scale laser powder bed fusion via a stacking model

Determining appropriate process parameters in large-scale laser powder bed fusion(LPBF)additive manufacturing pose formidable challenges that necessitate advanced approaches to minimize trial-and-error during experimentation.This work proposed a data-driven approach based on stacking ensemble learning to predict the mechanical properties of Ti6Al4V alloy fabricated by large-scale LPBF for the first time.This method can adapt to the complexity of large-scale LPBF data distribution and exhibits a more generalized predictive capability compared to base models.Specifically,the stacking model utilized artificial neural network(ANN),gradient boosting regressor,kernel ridge regression,and elastic net as base models,with the Lasso model serving as the meta-model.Bayesian optimization and cross-validation were utilized for model optimization and training based on a limited data set,resulting in higher predictive accuracy compared to traditional artificial neural network model.The statistical analysis of the ANN and stacking models indicates that the stacking model exhibits superior performance on the test set,with a coefficient of determination value of 0.944,mean absolute percentage error of 2.51%,and root mean squared error of 27.64,surpassing that of the ANN model.All statistical metrics demonstrate superiority over those obtained from the ANN model.These results confirm that by integrating the base models,the stacking model exhibits superior predictive stability compared to individual base models alone,thereby providing a reliable assessment approach for predicting the mechanical properties of metal parts fabricated by the LPBF process.

Long-term kidney transplant outcomes in Chinese patients with primary glomerulonephritis:A multicenter study in China

To the Editor:The primary cause of end-stage kidney disease(ESKD)in China is chronic glomerulonephritis(GN),which accounts for 45%of ESKD patients.[1]There is currently no nationwide large-scale study on the longterm prognosis of kidney transplantation in patients with chronic GN in China.Over the past decade,however,few landmark studies from populations in Europe[2,3]and the United States[4]have provided important reference data for this issue.Therefore,we propose to conduct a nationwide multicenter retrospective study,which was launched by the National Clinical Research Center of Kidney Diseases,Jinling Hospital,Nanjing University School of Medicine,from 2017 to 2020.

Efficacy of initial dose botulinum toxin A injection in acute concomitant esotropia with different clinical characteristics

To the Editor:Acute concomitant esotropia(ACE)is an acquired esotropia with a sudden appearance and no pathologic changes on cerebral imaging.There are various treatments for ACE,including extraocular muscle surgery,botulinum toxin A(BTA)injection,prisms,and divergence training.[1]BTA had been used in the treatment of ACE since it was approved by Food and Drug Administration(FDA,USA)in 1989.[2]Some researchers have confirmed that its effect is stable and has unique advantages in the treatment of ACE.

Specific pupylation as IDEntity reporter(SPIDER)for the identification of protein-biomolecule interactions

Protein-biomolecule interactions play pivotal roles in almost all biological processes.For a biomolecule of interest,the identification of the interacting protein(s)is essential.For this need,although many assays are available,highly robust and reliable methods are always desired.By combining a substrate-based proximity labeling activity from the pupylation pathway of Mycobacterium tuberculosis and the streptavidin(SA)-biotin system,we developed the Specific Pupylation as IDEntity Reporter(SPIDER)method for identifying protein-biomolecule interactions.Using SPIDER,we validated the interactions between the known binding proteins of protein,DNA,RNA,and small molecule.We successfully applied SPIDER to construct the global protein interactome for m^(6)A and m RNA,identified a variety of uncharacterized m^(6)A binding proteins,and validated SRSF7 as a potential m^(6)A reader.We globally identified the binding proteins for lenalidomide and Cob B.Moreover,we identified SARS-CoV-2-specific receptors on the cell membrane.Overall,SPIDER is powerful and highly accessible for the study of proteinbiomolecule interactions.

Cytomegalovirus Pneumonia in Patients with Rheumatic Diseases After Immunosuppressive Therapy： A Single Center Study in China

Background： Rheumatic diseases involve multiple organs that are affected by immunological mechanisms.Treatment with corticosteroids and immunosuppressive agents may also increase the frequency of infection.Cytomegalovirus （CMV） is a widespread herpes virus and a well-recognized pathogen, which causes an opportunistic and potentially fatal infection in immunocompromised patients.This retrospective study aimed to investigate the clinical and laboratory characteristics of CMV pneumonia in patients with rheumatic diseases after immunosuppressive therapy in a single center in Shanghai, China.Methods： Eight hundred and thirty-four patients with rheumatic diseases who had undergone CMV-DNA viral load tests were included, and the medical records of 142 patients who were positive for CMV-DNA in plasma samples were evaluated.GraphPad Prism version 5.013 （San Diego, CA, USA） was used to conduct statistical analysis.The correlation between CMV-DNA viral loads and lymphocyte counts was assessed using the Spearman rank correlation coefficient test.Significance between qualitative data was analyzed using Pearson＆#39;s Chi-squared test.The cut-offthresholds for CMV-DNA viral load and lymphocyte count were determined by receiver operating characteristic （ROC） curve analysis.Results： One hundred and forty-two patients had positive CMV viral load tests.Of these 142 patients, 73 patients with CMV pneumonia were regarded as symptomatic, and the other 69 were asymptomatic.The symptomatic group received higher doses ofprednisolone （PSL） and more frequently immunosuppressants than the asymptomatic group （P 〈 0.01）.The symptomatic group had lower lymphocyte counts, especially CD4＋ T-cells, than the asymptomatic group （P 〈 0.01）.By ROC curve analysis, when CD4＋ T-cell count was 〈0.39 ＆#215; 109/L, patients with rheumatic diseases were at high risk for symptomatic CMV infection.The CMV-DNA load was significantly higher in the symptomatic patients than that in asymptomatic patients （P 〈 0.01;threshold viral loads： 1.75 ＆#215; 104 copies/ml）.Seven patients had a fatal outcome, and they had lower peripheral lymphocyte counts （P 〈 0.01）, including CD4＋ and CD8＋ T-cells （P 〈 0.0 l）.Conclusions： When CD4＋ T-cell count is 〈0.39 ＆#215; 109/L, patients are at high risk for pulmonary CMV infection.Patients are prone to be symptomatic with CMV-DNA load 〉1.75 ＆#215; 104 copies/ml.Lymphopenia （especially CD4＋ T-cells）, presence of symptoms, and other infections, especially fungal infection, are significant risk factors for poor outcome, and a higher PSL dosage combined with immunosuppressants may predict CMV pneumonia.

One-stage dorsal lingual mucosal graft urethroplasty for the treatment of failed hypospadias repair

The aim of this study was to retrospectively investigate the outcomes of patients who underwent one-stage onlay or inlay urethroplasty using a lingual mucosal graft （LMG） after failed hypospadias repairs. Inclusion criteria included a history of failed hypospadias repair, insufficiency of the local skin that made a reoperation with skin flaps difficult, and necessity of an oral mucosal graft urethroplasty. Patients were excluded if they had undergone a failed hypospadias repair using the foreskin or a multistage repair urethroplasty. Between January 2008 and December 2012, 110 patients with failed hypospadias repairs were treated in our center. Of these patients, 56 underwent a one-stage onlay or inlay urethroplasty using LMG. The median age was 21.8 years （range： 4-45 years）. Of the 56 patients, one-stage onlay LMG urethroplasty was performed in 42 patients （group 1）, and a modified Snodgrass technique using one-stage inlay LMG urethroplasty was performed in 14 （group 2）. The median LMG urethroplasty length was 5.6 ± 1.6 cm （range： 4-13 cm）. The mean follow-up was 34.7 months （range： 10-58 months）, and complications developed in 12 of 56 patients （21.4%）, including urethrocutaneous fistulas in 7 （6 in group 1, 1 in group 2） and neourethral strictures in 5 （4 in group 1, 1 in group 2）. The total success rate was 78.6%. Our survey suggests that one-stage onlay or inlay urethroplasty with LMG may be an effective option to treat the patients with less available skin after failed hypospadias repairs; LMG harvesting is easy and safe, irrespective of the patient＇s age.

Adding a vacuum erection device to regular use of Tadalafil improves penile rehabilitation after posterior urethroplasty

This study aimed to evaluate whether adding a vacuum erection device(VED)to regular use of Tadalafil could achieve better penile rehabilitation following posterior urethroplasty for pelvic fracture-related urethral injury(PFUI).Altogether,78 PFUI patients with erectile dysfunction(ED)after primary posterior urethroplasty were enrolled and divided into two treatment groups:VED combined with Tadalafil(Group 1,n=36)and Tadalafil only(Group 2,n=42).Changes in penile length,testosterone level,International Index of Erectile Function-5(IIEF-5)questionnaire,Quality of Erection Questionnaire(QEQ),and nocturnal penile tumescence(NPT)testing were used to assess erectile function before and after 6 months of ED treatment.Results showed that the addition of VED to regular use of Tadalafil preserved more penile length statistically(0.4±0.9 vs-0.8±0.7 cm,P<0.01).IIEF-5 score and QEQ score in Group 1 were higher than Group 2(both P<0.05).After treatment,21/36(5&3%)Group 1 patients and 19/42(45.2%)Group 2 patients could complete vaginal penetration.Group 1 patients also had markedly improved testosterone levels(P=0.01).Unexpectedly,there was no significant difference in NPT testing between two therapies.For PFUI patients with ED after posterior urethroplasty,the addition of VED to regular use of Tadalafil could significantly improve their conditions-improving erection and increasing penile length-thus increasing patient satisfaction and confidence in penile rehabilitation.

Modular Click Chemistry Library:Searching for Better Functions

High throughput screening towards chemical libraries is the primary way to discover lead compounds in developing innovative drugs,especially new molecular entities.Accordingly,the preparation of chemical libraries is the key step for drug development.Now,con-ventional small molecule chemical libraries and DNA-encoded chemical libraries are the main models of chemical libraries for high-throughput screening.Recently,a new model of chemical library,calledmodular click chemistry library,was proposed,which gives us an alternative choice to construct chemical libraries for high throughput screening and exhibits broad prospects to accelerate drug development.Herein,this article mainly focuses on the strategy to prepare the modular click chemistry library.

SOLUTION OF MULTIPLE CRACKS IN A FINITE PLATE OF AN ELASTIC ISOTROPIC MATERIAL WITH THE DISTRIBUTED DISLOCATION METHOD

This paper presents a numerical solution to model multiple cracks in a finite plate of an elastic isotropic material. Both the boundaries and the cracks are modeled by distributed dislocations. This method results in a system of singular integral equations with Cauchy kernels which can be solved by Gauss-Chebyshev quadrature method. Four examples are provided to assess the capability of this method.

Numerical Approaches for Linear Left-invariant Diffusions on SE(2), their Comparison to Exact Solutions, and their Applications in Retinal Imaging

Left-invariant PDE-evolutions on the roto-translation group SE(2)(and their resolvent equations)have been widely studied in the fields of cortical model-ing and image analysis.They include hypo-elliptic diffusion(for contour enhance-ment)proposed by Citti&Sarti,and Petitot,and they include the direction process(for contour completion)proposed by Mumford.This paper presents a thorough study and comparison of the many numerical approaches,which,remarkably,are missing in the literature.Existing numerical approaches can be classified into 3 categories:Finite difference methods,Fourier based methods(equivalent to SE(2)-Fourier methods),and stochastic methods(Monte Carlo simulations).There are also 3 types of exact solutions to the PDE-evolutions that were derived explicitly(in the spatial Fourier domain)in previous works by Duits and van Almsick in 2005.Here we provide an overview of these 3 types of exact solutions and explain how they relate to each of the 3 numerical approaches.We compute relative errors of all nu-merical approaches to the exact solutions,and the Fourier based methods show us the best performance with smallest relative errors.We also provide an improvement of Mathematica algorithms for evaluating Mathieu-functions,crucial in implemen-tations of the exact solutions.Furthermore,we include an asymptotical analysis of the singularities within the kernels and we propose a probabilistic extension of un-derlying stochastic processes that overcomes the singular behavior in the origin of time-integrated kernels.Finally,we show retinal imaging applications of combining left-invariant PDE-evolutions with invertible orientation scores.

Enhanced and tunable fluorescent quantum dots within a single crystal of protein

The design and synthesis of bio-nano hybrid materials can not only provide new materials with novel properties, but also advance our fundamental understanding of interactions between biomolecules and their abiotic counterparts. Here, we report a new approach to achieving such a goal by growing CdS quantum dots （QDs） within single crystals of lysozyme protein. This bio-nano hybrid emitted much stronger red fluorescence than its counterpart without the crystal, and such fluorescence properties could be either enhanced or suppressed by the addition of Ag（I） or Hg（II）, respectively. The three-dimensional incorporation of CdS QDs within the lysozyme crystals was revealed by scanning transmission electron microscopy with electron tomography. More importantl~ since our approach did not disrupt the crystalline nature of the lysozyme crystals, the metal and protein interactions were able to be studied by X-ray crystallography, thus providing insight into the role of Cd（II） in the CdS QDs formation.

Occurance and control of manganese in a large scale water treatment plant

The continuous variations of dissolved oxygen （DO）, manganese （Mn）, pH, and their effect on manganese removal by different water treatment processes are investigated. The results show that the declined DO concentration and pH value in the bottom of reservoir results in the increasing release of Mn from sediment to source water. Manganese concentration increased from 0.1 to 0.4 mg. L i under the condition that DO concentration decreased from 12.0 to 2.0mg.LI in raw water. The different water treatment processes exhibited different efficiency on manganese removal. The processes with recycling of the suspended sludge, low elevation velocity in settling tank and slow filter rate, will benefit the manganese removal. During a high release of manganese in raw water, traditional coagulation-sedimentation and filtration could not completely remove Mn, although granular activated carbon filtration （GAC） had been applied. At that case, preoxidation with chlorine or potassium permanganate （KMnO4） was necessary to address the high manganese concentration.