Backbone-Enabled and Ester Groups Switched δ-C(sp2)-H Amination/Fluorination: Cyclic Dipeptides Synthesis.

An efficient and concise strategy for the synthesis of cyclic dipeptides via Pd-catalyzed site-selective δ-C(sp2)-H amination/fluorination and N-to-C cyclization is disclosed. The backbone amides within the dipeptides serves as endogenous directing groups, while the desired products were switched by the C-terminal ester group. This chemistry presents a novel and robust alternative to construct cyclodipeptide fragments.

Elbow hemiarthroplasty with a 3D-printed prosthesis for distal humeral bone defects after tumor excision: a case report.

INTRODUCTION: The distal humerus is a rare site for primary and metastatic bone tumors. Due to the scarcity of cases and lack of standardized surgical strategies, it is often difficult for surgeons to choose the right choice. The application of a 3D-printed prosthesis with hemiarthroplasty for the treatment of the distal humerus after tumor resection can be a very effective option. CASE PRESENTATION: We present a clinical case of a 3D-printed distal humeral prosthesis for the treatment of bone defects caused by metastatic bone tumors. The preoperative evaluation was aggressively performed, and the decision was made to distal humeral hemiarthroplasty (DHH) after wide resection of the tumor segment bone. Processing of the Digital Imaging and Communications in Medicine (DICOM) data from CT scans performed after mirror conversion using CT data of the contralateral humerus, we designed a 3D-printed distal humeral prosthesis with hemiarthroplasty. After reconstruction of bone and surrounding soft tissue by the 3D-printed prosthesis combined with the LARS ligament and regular follow-up for 12 months, the patient had an MSTS-93 score of 29 and an MEP of 100, which reached a good level, and the patient was fully competent in normal daily activities. CONCLUSIONS: Our results show that the 3D-printed modular prosthesis with hemiarthroplasty is a very effective option for cases of large elbow bone defects due to primary bone tumors or metastatic disease. However, careful preoperative preparation is required for the best outcome. Careful preoperative preparation and long-term follow-up are essential for the best outcome.

Enhancing nitrate attenuation in groundwater via selectively applying surface agricultural practices: A novel and sustainable strategy for non-point source pollution mitigation.

Non-point nitrate pollution in groundwater has been accelerated by agricultural development, but sustainable nitrogen removal is a challenge because of its wide distribution and negative side effects. Surface agricultural practices (SAPs), which are demonstrably effective in driving the downward infiltration of dissolved organic carbon (DOC), have not been well explored for their potential to enhance nitrate attenuation in groundwater. Therefore, a combination of soil column and groundwater incubation experiments was performed to investigate the carbon and nitrogen responses to different SAPs (manure fertilization, lucerne planting, and straw return). The soil column experiment showed that SAPs promoted DOC and reduced nitrate leaching into groundwater, and straw treatment witnessed the highest DOC leaching flux (252.71 g m-2 yr-1) and lowest nitrate leaching flux (9.51 g m-2 yr-1). The groundwater incubation experiment showed that leachates from the straw treatment displayed the best denitrification-enhancement performance, with the highest NO3--N reduction efficiency (92.93%) and rate (1.627 mg/day), N2 selectivity (99.78%), and net nitrogen removal (0.09 mg). Furthermore, Fourier transform ion cyclotron resonance mass spectrometry confirmed that CHOS molecules with lower double bond equivalents (0-5) and larger carbon numbers (10-15) were more accessible to denitrifiers. This study provides a new path for the sustainable control of non-point source nitrate pollution.

Cryptotanshinone Suppressed Postmenopausal Osteoporosis by Preventing RANKL-Mediated Osteoclastogenesis against Kidney Injury.

BACKGROUND: Cryptotanshinone (CPT), an active component extracted from the root of Salvia miltiorrhiza Bunge, exhibits extensive favorable bioactive properties including anti-inflammatory, antioxidative, antibacterial, and antitumor effects. This study aims to investigate the effects of CPT on osteogenesis and explore related mechanisms both in vivo and in vitro. METHODS: In the in vivo experiment, ovariectomized (OVX) female rats were intragastrically administered with CPT at doses of 10 mg/kg and 20 mg/kg for 13 consecutive weeks. Dual-energy X-ray absorptiometry was employed to detect bone mineral density (BMD). ELISA assay was leveraged to detect the biochemical parameters such as BUN and creatinine in the kidney samples. Bone and kidney sections were dyed by H&E and Masson staining kits. In the in vitro experiment, the RAW 264.7 cells were stimulated through the receptor activation of the nuclear factor kappa B ligand (RANKL) to establish an osteoclast differentiation model, and CPT's protective effect against bone loss was evaluated. Differentiated osteoclasts were determined by TRAP staining. While, osteoclast-marker proteins such as NFATc1, c-Fos, and cathepsin K were identified by Western blot. RESULTS: The results from in vivo experiments revealed that CPT could elevate bone mass and increase bone formation markers in OVX rats. Intriguingly, CPT administration noticeably ameliorated the kidney injury in OVX rats by suppressing BUN and restoring creatinine levels. Furthermore, the results from in vitro experiments suggested that CPT downregulated the protein expression of osteoclast-associated genes such as cathepsin K, c-Fos, and NFATc1 which hinted the related potential mechanisms. CONCLUSION: The evidence from in vivo and in vitro experiments suggested that CPT exerted antiosteoclastogenic effects by inhibiting the activation of osteoclast differentiation followed by suppressing the protein expressions of cathepsin K, c-Fos, and NFATc1 in osteoclast precursors, and it exhibited protective effects against kidney damage, which highlighted its advantage in clinical application.

Age-specific reference intervals of serum anti-Müllerian hormone in Chinese girls.

BACKGROUND: This study aimed to establish anti-Mullerian hormone age-specific reference intervals and determine the correlation between the anti-Mullerian hormone concentration and age, body mass index and concentrations of follicle-stimulating hormones and luteinizing hormone in healthy Chinese girls. METHODS: Serum anti-Mullerian hormone concentrations of 1702 healthy girls (0-12 years), recruited between March 2018 and December 2019, were determined using the Beckman Access 2 automated chemiluminescence immunoassay. Single-year-specific medians of anti-Mullerian hormone and effects of age, body mass index, follicle-stimulating hormone and luteinizing hormone on anti-Mullerian hormone concentration were analysed. RESULTS: The anti-Mullerian hormone median level continued increasing from birth, reached its peak at age 9 at 4.45 ng/mL (interquartile range [IQR] 2.58-6.90) and then gradually decreased. At age 12, the median reached 1.98 ng/mL (IQR 1.05-3.46). Age-specific reference intervals for anti-Mullerian hormone were established in healthy Chinese girls aged 0-12 years. Anti-Mullerian hormone concentrations showed a moderately positive correlation with age (r = 0.33, P < 0.001). In contrast, follicle-stimulating hormone (r = -0.29, P < 0.001) concentrations were weakly negatively correlated with the serum anti-Mullerian hormone concentration. CONCLUSION: We established single-year-specific reference intervals for anti-Mullerian hormone in Chinese girls using the Beckman chemiluminescent platform. This reference range can help clinicians accurately understand anti-Mullerian hormone secretion in healthy girls and promote its clinical use.

Age-specific reference intervals for anti-Müllerian hormone in Chinese boys: A population-based study.

BACKGROUND: Anti-Müllerian hormone (AMH) is used for evaluating gonadal development and testicular function. We aimed to establish AMH reference intervals and to determine the correlations between AMH level and age, body mass index (BMI), and follicle stimulating hormone (FSH), luteinizing hormone (LH), and total testosterone (TT) levels in healthy Chinese boys. METHODS: Serum AMH levels of 2,009 healthy boys (age, 0-14 years), recruited between October 2017 and April 2019, were determined using the Beckman Access 2 automated chemiluminescence immunoassay. Single-year-specific median, mean, and standard deviation (SD) of AMH and effects of age, BMI, FSH, LH, and TT on the AMH level were analyzed. RESULTS: The median and mean ± SD values of AMH increased slightly after birth. Serum AMH values decreased sharply at 2 years of age and were 6-7% of the birth level at 12 years, after which they remained low. Age-specific AMH reference intervals were established. Significant negative correlations were observed between AMH level and age (r = -0.75, P < 0.001); serum AMH levels were moderately negatively correlated with BMI (r = -0.35, P < 0.001), FSH (r = -0.37, P < 0.001), and TT (r = -0.45, P < 0.001) levels; and correlation with LH (r = -0.18, P < 0.001) was the weakest. In contrast, correlations between AMH and the LH/FSH ratio were not observed. CONCLUSION: We established single-year-specific reference intervals for AMH in Chinese boys. Our findings revealed the changes in AMH secretion during normal male growth, and may provide a basis for the clinical use of AMH.