Spermidine-Functionalized Injectable Hydrogel Reduces Inflammation and Enhances Healing of Acute and Diabetic Wounds In Situ.

The inflammatory response is a key factor affecting tissue regeneration. Inspired by the immunomodulatory role of spermidine, an injectable double network hydrogel functionalized with spermidine (DN-SPD) is developed, where the first and second networks are formed by dynamic imine bonds and non-dynamic photo-crosslinked bonds respectively. The single network hydrogel before photo-crosslinking exhibits excellent injectability and thus can be printed and photo-crosslinked in situ to form double network hydrogels. DN-SPD hydrogel has demonstrated desirable mechanical properties and tissue adhesion. More importantly, an "operando" comparison of hydrogels loaded with spermidine or diethylenetriamine (DETA), a sham molecule resembling spermidine, has shown similar physical properties, but quite different biological functions. Specifically, the outcomes of 3 sets of in vivo animal experiments demonstrate that DN-SPD hydrogel can not only reduce inflammation caused by implanted exogenous biomaterials and reactive oxygen species but also promote the polarization of macrophages toward regenerative M2 phenotype, in comparison with DN-DETA hydrogel. Moreover, the immunoregulation by spermidine can also translate into faster and more natural healing of both acute wounds and diabetic wounds. Hence, the local administration of spermidine affords a simple but elegant approach to attenuate foreign body reactions induced by exogenous biomaterials to treat chronic refractory wounds.

The effect of previous induced abortion history on the assisted reproduction outcomes.

PURPOSE: To study whether the history of induced abortion has an effect on the assisted reproduction outcomes in patients undergoing in vitro fertilization-embryo transfer (IVF-ET). METHODS: 3045 patients who underwent IVF-ET in the Department of Human Reproductive Center of Renmin Hospital from January 2017 to June 2021. They were divided into two groups according to whether there was a history of induced abortion in the past, and the outcomes were compared between the two groups. RESULTS: The clinical pregnancy rate in the group with induced abortion history was lower than that in the group without induced abortion history (63.1% vs 67.1%), but the difference was not statistically significant (P = 0.059). The spontaneous abortion rate in the group with induced abortion history was higher than that in the group without induced abortion history (14.9% vs 11.2%) (P = 0.044). The live birth rate in the group with induced abortion history was lower than that in the group without induced abortion history (52.8% vs 59.0%) (P = 0.006). Stepwise logistic regression analysis showed that endometrial thickness (OR = 0.928, 95% CI = 0.886 ~ 0.972, P = 0.002) and live birth rate (OR = 0.682, 95% CI = 0.495 ~ 0.939, P = 0.019) were negatively correlated with induced abortion history. The rate of spontaneous abortion (OR = 1.452, 95% CI = 1.042 ~ 2.024, P = 0.028) was positively correlated with the history of induced abortion. CONCLUSIONS: The previous history of induced abortion is related to the outcomes of IVF /ICSI-ET, the endometrial thickness on HCG trigger day decreased, the risk of spontaneous abortion increased and the live birth rate decreased in patients with induced abortion history when undergoing IVF/ICSI-ET.

The comparison between fixed versus degressive doses of medroxyprogesterone acetate combined with letrozole in patients of progestin-primed ovarian stimulation protocol: a propensity score-matched study.

Objective: To explore the cycle characteristics and pregnancy outcomes of progestin-primed ovarian stimulation (PPOS) using fixed versus degressive doses of medroxyprogesterone acetate (MPA) in conjunction with letrozole (LE) in infertile women by propensity score matching (PSM) analysis. Design: A retrospective cohort study. Setting: Tertiary-care academic medical center. Population: A total of 3173 infertile women undergoing their first in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) treatment within the period from January 2017 to December 2020. Methods: A total of 1068 and 783 patients who underwent a fixed dose of MPA combined with LE and a degressive dose of MPA combined with LE protocols, respectively, were enrolled in this study. The freeze-all approach and later frozen-thawed embryo transfer (FET) were performed in both groups. Propensity score matching (1:1) was performed. Main outcome measures: The primary outcomes were the dosage of MPA and the incidence of premature luteinizing hormone (LH) surges. The secondary outcomes were the number of oocytes retrieved, the cumulative live birth rate (CLBR) and the fetal malformation rate. Results: We created a perfect match of 478 patients in each group. The dosage of MPA, the LH serum level on the eighth day of stimulation, progesterone (P) level and LH level on the hCG trigger day were significantly higher in the LE + fixed MPA group than in the LE + degressive MPA group (52.1 ± 13.1 mg vs. 44.9 ± 12.5 mg; 5.0 ± 2.7 IU/L vs. 3.7 ± 1.7 IU/L; 0.9 ± 0.5 ng/ml vs. 0.8 ± 0.5 ng/ml; 3.3 ± 2.4 IU/L vs. 2.8 ± 1.9 IU/L; P < 0.01). The duration of Gn, the number of follicles with diameter more than 16 mm on trigger day, the estradiol (E2) level on the hCG trigger day were lower in the LE + fixed MPA group than in the LE + degressive MPA group (9.7 ± 1.7 days vs. 10.3 ± 1.5 days; 5.6 ± 3.0 vs. 6.3 ± 3.0; 1752.5 ± 1120.8 pg/ml vs. 1997.2 ± 1108.5 pg/ml; P < 0.001). No significant difference was found in the incidence of premature LH surge, the number of oocytes retrieved, the number of top-quality embryos, clinical pregnancy rate (CPR), CLBR or fetal malformation rate between the two groups. Conclusion: The combination of a degressive MPA dose with LE proved effective in reducing the total MPA dosage with comparable premature LH surge and pregnancy outcomes in women undergoing the PPOS protocol.

The serum oestradiol/progesterone ratio on the day of OPU + 7, but not the day of OPU + 5, affects the rates of live birth in fresh blastocyst embryo transfer cycles.

BACKGROUND: In an in vitro fertilization (IVF) cycle, the embryo ends its wandering time and begins the process of implantation into the uterine cavity on the seventh day after oocyte pick-up (OPU + 7), which is closer than OPU + 5 to the time of nidation. Therefore, measuring the oestradiol (E2)/progesterone (P) ratio on OPU + 7 may be helpful for predicting pregnancy outcomes. METHODS: This is a retrospective cohort study of 2,257 women undergoing a follicular-phase depot gonadotropin-releasing hormone agonist (GnRH-a) protocol for in vitro fertilization /intracytoplasmic sperm injection (IVF/ICSI) treatment and fresh blastocyst embryo transfer cycles at a university-affiliated fertility center between January 2016 and April 2021. First, 2,257 women were split into two groups based on clinical pregnancy for analyzing the levels of E2 and P and the E2/P ratio on the day of OPU + 2, OPU + 5 and OPU + 7. And then 2,257 cycles were stratified into three groups based on E2/P ratio tertiles on OPU + 7: the low group (1.3-15.7 pg/ng), middle group (15.7-28.8 pg/ng), and high group (28.8-487.2 pg/ng). The threshold effect of the E2/P ratio on OPU + 7 on live birth was investigated using a two-piecewise linear regression model and a smoothing function curve. RESULTS: The level of P in the clinical pregnancy group were lower than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (201.9 ± 71.6 ng/ml vs 213.1 ± 77.6 ng/ml, 89.5 ± 88.5 ng/ml vs 99.5 ± 94.9 ng/ml, P < 0.05). The E2/P ratio in the clinical pregnancy group were higher than that in the nonclinical pregnancy group on both OPU + 2 and OPU + 7 (8.4 ± 6.5 pg/ng vs 8.0 ± 6.8 pg/ng, 32.3 ± 38.5 pg/ng vs 25.2 ± 31.0 pg/ng, P < 0.01). The E2/P ratio on OPU + 7 was positively associated with positive hCG (adjusted OR = 1.01; 95% CI, 1.01-1.02; P < 0.0001), clinical pregnancy (adjusted OR = 1.01; 95% CI, 1.00-1.01; P = 0.0067) and live birth (adjusted OR = 1.01; 95% CI, 1.00-1.01; P < 0.001), and a nonlinear correlation was observed between the E2/P ratio and LBR on OPU + 7. CONCLUSIONS: A higher E2/P ratio is associated with a higher LBR, but the E2/P ratio should be maintained within a suitable range.

The follicular-phase depot GnRH agonist protocol results in a higher live birth rate without discernible differences in luteal function and child health versus the daily mid-luteal GnRH agonist protocol: a single-centre, retrospective, propensity score matched cohort study.

BACKGROUND: The gonadotropin-releasing hormone agonist (GnRH-a) has been used in in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI) cycles for a long time. This paper evaluates the efficacy and safety of two commonly used protocols (follicular-phase depot GnRH-a protocol and daily mid-luteal long GnRH-a protocol) in normal responders undergoing IVF/ICSI using propensity score matching (PSM) analysis. METHODS: A total of 6,816 infertile women treated within the period from January 2016 to September 2020 were stratified into cohorts. A total of 2,851 patients received the long-acting group (depot GnRH-a protocol), and 1,193 used the short-acting group (long GnRH-a protocol) after the data-selection process. PSM was utilized for sampling by up to 1:1 nearest neighbour matching to adjust the numerical difference and balance the confounders between groups. The primary outcome was the live birth rate (LBR). Multivariable logistic analysis was used to evaluate the difference between these two protocols in relation to the LBR. RESULT(S): In this study, 1:1 propensity score matching was performed to create a perfect match of 964 patients in each group. After matching, the blastocyst formation rates, oestradiol (E2) value on Day hCG + 9, progesterone (P) value on Day hCG + 9, implantation rates, clinical pregnancy rates, and LBR were more favourable in the depot GnRH-a protocol than in the long GnRH-a protocol (P < 0.05). However, the moderate or severe OHSS rates were higher in the depot group than in the long group (P < 0.001). There were no significant differences in endometrial thickness, luteal support medication, early pregnancy loss rates, mid- and late-term pregnancy loss rates, or foetal malformation rates between the two protocols. CONCLUSION(S): Compared with the daily short-acting GnRH agonist protocol, the follicular-phase depot GnRH-a protocol might improve LBRs in normogonadotropic women without discernible differences in luteal function and child health.

Catalytic stereoselective cascade reactions of quinols with trifluoromethyl ketones: direct access to CF3-containing 1,3-dioxolanes.

A general and efficient synthesis of CF3-containing 1,3-dioxolanes using Et3N-catalyzed ketalization/oxa-Michael cascade of quinols with trifluoromethyl ketones is described. The reaction works efficiently under mild reaction conditions and produces the desired products in 68%-95% yields with acceptable diastereoselectivities. In addition, the reaction proceeds smoothly to give the desired product 3a in 92% yield and with high ee (80%) in the presence of a chiral catalyst (DHQ)2PHAL.

Asymmetric Synthesis of P-Stereogenic Phosphinic Amides via Pd(0)-Catalyzed Enantioselective Intramolecular C-H Arylation.

The palladium-catalyzed enantioselective intramolecular C-H arylation of N-(2-haloaryl)-P,P-diphenylphosphinic amides furnishes P-stereogenic phosphine oxide derivatives in 61-99% yield with 88-97% ee. The catalyst generated in situ from a TADDOL-derived phosphoramide ligand and Pd(dba)2 is optimum in terms of yield and enantioselectivities.

Silver salts and DBU cooperatively catalyzed nucleophilic addition/cyclization of propargylic alcohols with trifluoromethyl ketones.

A general and efficient synthesis of trifluoromethyl substituted 5-alkylidene-1,3-dioxolane using a silver salt and DBU cooperatively catalyzed nucleophilic addition/cyclization of propargylic alcohols and trifluoromethyl ketones is described. The procedure produced 5-alkylidene-1,3-dioxolane derivatives with good to excellent yields and can be used with a broad range of substrates.

Asymmetric synthesis of planar chiral ferrocenes by enantioselective intramolecular C-H arylation of N-(2-haloaryl)ferrocenecarboxamides.

The palladium-catalyzed intramolecular C-H arylation reaction of N-(2-bromoaryl)ferrocenecarboxamides furnishes planar chiral ferrocene derivatives. TADDOL-derived phosphoramide ligands induce enantioselectivities ranging from 91:9 to 98:2 er.

Evaluation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol for catalytic asymmetric addition of organozinc reagents to aldehydes.

A facile and practical approach to preparation of enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was developed from cheap and easily available l-(+)-methionine. Synthetic highlights include the three-step, one-pot construction of the chiral azetidine ring and the development of an improved one-step procedure for the synthesis of the key intermediate l-2-amino-4-bromobutanoic acid. Enantiopure N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol was evaluated for catalytic asymmetric addition of organozinc reagents to aldehydes. The asymmetric ethylation, methylation, arylation, and alkynylation of aldehydes achieved enantioselectivity of up to 98.4%, 94.1%, 99.0%, and 84.6% ee, respectively, in the presence of a catalytic amount of chiral N-(ferrocenylmethyl)azetidin-2-yl(diphenyl)methanol. Our results demonstrated further that the four-membered heterocycle-based backbone was a good potential chiral unit for the catalytic asymmetric induction reaction, and the hindrance of the bulky ferrocenyl group, compared to a phenyl group, played an important role in the enantioselectivities. A possible transition for the catalytic asymmetric addition has been proposed on the basis of the crystal structure of the chiral ligand 3b including two HOAc molecules and previous studies.

catena-Poly[[[diaqua-iron(II)]-µ-pyridine-2,5-dicarboxyl-ato-[tetra-aqua-iron(II)]-µ-pyridine-2,5-dicarboxyl-ato] tetra-hydrate].

In the crystal structure of the title compound, {[Fe(2)(C(7)H(3)NO(4))(2)(H(2)O)(6)]·4H(2)O}(n), there are two types of coordination for the Fe(II) atoms. One Fe(II) atom is in a distorted octa-hedral N(2)O(4) environment, with two chelating rings from the pyridine-dicarboxyl-ate ligands and two O atoms from the water mol-ecules, while the other is in a distorted octa-hedral O(6) environment with two O atoms from the pyridine-dicarboxyl-ate ligands and four O atoms from the water mol-ecules. Both Fe(II) atoms lie on crystallographic centers of symmetry. The complex possesses an infinite chain structure running along the [101] direction. These chains are inter-connected by the uncoordinated water mol-ecules through O-H⋯O hydrogen bonds.

1,1'-[o-Phenyl-enebis(nitrilo-methyl-idyne)]di-2-naphthol ethanol hemisolvate.

The asymmetric unit of the title compound, C(28)H(20)N(2)O(2)·0.5C(2)H(5)OH, contains two independent mol-ecules of 1,1'-[o-phenyl-enebis(nitrilo-methyl-idyne)]di-2-naphthol, denoted A and B, and one ethanol solvent mol-ecule. The hydr-oxy groups are involved in intra-molecular O-H⋯N hydrogen bonds influencing the mol-ecular conformations, which are slightly different in mol-ecules A and B, where the two bicyclic systems form dihedral angles of 51.93 (9) and 58.52 (9)°, respectively. In the crystal structure, a number of short inter-molecular C⋯C contacts with distances of less than 3.5 Šsuggest the existence of π-π inter-actions, which contribute to the stability of the crystal packing.

catena-Poly[[[diaqua-iron(II)]-µ-pyrazine-2,3-dicarboxyl-ato] dihydrate].

The crystal structure of the title compound, {[Fe(C(6)H(2)N(2)O(4))(H(2)O)(2)]·2H(2)O}(n), was synthesized by a diffusion method. It has a one-dimensional polymeric chain structure and the chains are further connected into a three-dimensional structure by hydrogen bonds. The Fe(II) ion has a distorted octa-hedral coordination environment, with two N and two O atoms from the pyrazine-2,3-dicarboxyl-ate ligands in the equatorial plane and with two water mol-ecules in axial positions. The Fe atom lies on a crystallographic centre of symmetry and a twofold rotation axis passes through the pyrazine ring.