Modular Synthetic Platform for Interior-Functionalized Dendritic Macromolecules Enabled by the Palladium/Norbornene Catalysis.

Synthesis of interior-functionalized dendritic macromolecules is generally tedious and labor-intensive, which has been a key factor hampering their practical applications. Here, we have revisited this long-standing challenge and devised a modular and convergent platform to synthesize multifunctional dendrons with all-carbon backbones up to four generations via an in situ functionalization strategy. Enabled by the palladium/norbornene cooperative catalysis, different functional groups can be introduced to each generation of dendrons during the dendron growth, making it convenient for systematic comparison of their properties. The utility of this versatile platform is further showcased in the internal-functionalization-dependent properties of dendrons as organogels and aggregation-induced emission materials.

Multicomponent Polymerization for π-Conjugated Polymers.

Structurally complex π-conjugated polymers hold great promise as key components in sensor and electronic devices; however, their syntheses have not been a trivial task. From a synthetic efficiency perspective, it would be more attractive to access these materials using convenient and efficient methods from simple building blocks. One such synthetic tool, multicomponent polymerization, can accommodate modularity and provide highly efficient syntheses. This feature article outlines several multicomponent polymerization strategies for the synthesis of various π-conjugated polymers, which are classified based upon how the monomers are aligned during polymerization. Additionally, the challenges and outlooks of this field are highlighted and discussed.

A comparison of postoperative outcomes after open and laparoscopic reduction of Petersen's Hernia: a multicenter observational cohort study.

BACKGROUND: The aim of this multicenter cohort study was to compare the clinical courses between open and laparoscopic Petersen's hernia (PH) reduction. METHOD: We retrospectively collected the clinical data of patients who underwent PH repair surgery after gastrectomy for gastric cancer from 2015-2018. Forty patients underwent PH reduction operations that were performed by six surgeons at four hospitals. Among the 40 patients, 15 underwent laparoscopic PH reduction (LPH), and 25 underwent open PH reduction (OPH), including 4 patients who underwent LPH but required conversion to OPH. RESULTS: We compared the clinical factors between the LPH and OPH groups. In the clinical course, we found no differences in operation times or intraoperative bowel injury, morbidity, or mortality rates between the two groups (p > 0.05). However, the number of days on a soft fluid diet (OPH vs. LPH; 5.8 vs. 3.7 days, p = 0.03) and length of hospital stay (12.6 vs. 8.2 days, p = 0.04) were significantly less in the LPH group than the OPH group. Regarding postoperative complications, the OPH group had a case of pneumonia and sepsis with multi-organ failure, which resulted in mortality. In the LPH group, one patient experienced recurrence and required reoperation for PH. CONCLUSION: Laparoscopic PH reduction was associated with a faster postoperative recovery period than open PH reduction, with a similar incidence of complications. The laparoscopic approach should be considered an appropriate strategy for PH reduction in selected cases.

A mouse model of retinal hypoperfusion injury induced by unilateral common carotid artery occlusion.

Retina, one of the highest oxygen demanding tissues, is vulnerable to vascular insufficiencies, and various ocular vascular disorders can cause chronic retinal ischemia. To investigate the pathophysiology, rodent models developed by bilateral common carotid artery occlusion (BCCAO) have been utilized. However, mice lack posterior communicating arteries in the circle of Willis and cannot endure the brain ischemia induced by the bilateral occlusion. A mouse model to better reflect the localized ischemic stress in the retina without affecting the brain is still needed. Here, we established a mouse model of ischemic injury by permanent unilateral common carotid artery occlusion (UCCAO). Adult male mice were subjected to UCCAO, and changes in the ipsilateral retina were examined in comparison with the contralateral retina. Delayed perfusion was observed in the ipsilateral retina right after the occlusion and was not recovered later on. Common features of retinal ischemia were observed: hypoxia-inducible factor (HIF) stabilization; upregulation of hypoxia-responsive genes; altered levels of cytokines and chemokines. Activation of astrocytes and Müller cells in the inner retina was detected at day 2, and thinning of the inner retinal layer became significant at week 10. Together, our model can simulate retinal ischemia with morphological and molecular changes. It can be utilized to investigate pathophysiology of ischemic retinopathies.

Laparoscopy-assisted versus Open D2 Distal Gastrectomy for Advanced Gastric Cancer: Results From a Randomized Phase II Multicenter Clinical Trial (COACT 1001).

OBJECTIVE: This randomized, phase II, multicenter clinical trial was conducted to evaluate the feasibility of laparoscopy-assisted distal gastrectomy (LADG) with D2 lymph node dissection compared with open distal gastrectomy (ODG) for the treatment of advanced gastric cancer (AGC). SUMMARY OF BACKGROUND DATA: D2 lymph node dissection has been accepted as standard treatment for AGC. Although LADG is widely performed in early gastric cancer (EGC), the feasibility of LADG in AGC has not been proven yet. METHODS: Patients with cT2-T4a and cN0-2 (AJCC 7 staging system) distal gastric cancer were randomly but not blindingly assigned to LADG or ODG groups using fixed block sizes with a 1:1 allocation ratio. The primary endpoint was the noncompliance rate of the lymph node dissection, which was used to evaluate feasibility. Secondary endpoints included 3-year disease-free survival (DFS), 5-year overall survival, complications, and surgical stress response. RESULTS: Between June 2010 and October 2011, 204 patients enrolled and underwent either LADG (n = 105) or ODG (n = 99). Of these, 196 patients (100 in LADG and 96 in ODG) were included in the intention-to-treat analysis. There were no significant differences in the overall noncompliance rate of lymph node dissection between LADG and ODG groups (47.0% and 43.2%, respectively; P = 0.648). In the subgroup analysis, the noncompliance rate in the LADG group was significantly higher than the ODG group for clinical stage III disease (52.0% vs 25.0%, P = 0.043). No difference was found in the 3-year DFS rate between the groups (LADG, 80.1%; ODG, 81.9%; P = 0.448). Differences in postoperative complication rates and surgical stress response were found to be insignificant between the 2 arms. CONCLUSIONS: LADG was feasible for AGC treatment based on the noncompliance rate of D2 lymph node dissection. Subgroups analysis data suggest that further studies are needed for stage III gastric cancer.

Modular In†Situ Functionalization Strategy: Multicomponent Polymerization by Palladium/Norbornene Cooperative Catalysis.

Herein, we report a cooperatively palladium/norbornene-catalyzed polymerization, which simplifies the synthesis of functional aromatic polymers, including conjugated polymers. Specifically, an A2 B2 C-type multicomponent polymerization that is based on an ortho amination/ipso alkynylation reaction was developed for the preparation of various amine-functionalized arylacetylene-containing polymers. Within a single catalytic cycle, the amine side chains are site-selectively installed in situ by C-H activation during the polymerization process, which represents a major difference from conventional cross-coupling polymerizations. This "in situ functionalization" strategy enables the modular incorporation of functional side chains starting from simple monomers, thereby conveniently affording a diverse range of functional polymers.

Efficient Bottom-Up Preparation of Graphene Nanoribbons by Mild Suzuki-Miyaura Polymerization of Simple Triaryl Monomers.

Herein an efficient bottom-up solution-phase synthesis of N=9 armchair graphene nanoribbons (GNRs) is described. Catalyzed by Pd(PtBu3 )2 , Suzuki-Miyaura polymerization of a simple and readily available triaryl monomer provides a novel GNR precursor with a high molecular weight and excellent solubility. Upon cyclodehydrogenation, the resulting GNR exhibits semiconducting properties with an approximately 1.1 eV band gap (LUMO: -3.52 eV; HOMO: -4.66 eV) as characterized by UV/Vis-NIR spectroscopy and cyclic voltammetry.

One-pot preparation of 3D nano- and microaggregates via in situ nanoparticlization of polyacetylene diblock copolymers produced by ROMP.

Zero-dimensional (0D) nanospheres, 1D nanocaterpillars, and 3D aggregates are produced from simple diblock copolymers containing polyacetylene (PA) via in situ nanoparticlization of conjugated polymers. The diblock copolymers are prepared by ring-opening metathesis polymerization via one-pot sequential addition of an endo-tricyclo[4.2.2.0]deca-3,9-diene (TD) and cyclooctatetraene. Initially, they spontaneously form nanospheres consisting of a PA core and PTD shell, and increasing the length of the PA block leads to the direct nanoparticlization of the higher-dimensional structures such as 1D and 3D aggregates because of the decreased effective volume ratio of the rigid PTD shell to the solvophobic PA core.

Clinical Safety and Efficacy Evaluation of a Dissolving Microneedle Patch Having Dual Anti-Wrinkle Effects With Safe and Long-Term Activities.

BACKGROUND: Anti-aging products are widely used, but the desire for safe and more efficient anti-aging products continues to increase. Dissolving microneedle patches (MNPs) have provided a more efficient transdermal drug delivery solution. MNP is a promising candidate for developing better anti-aging products. OBJECTIVE: To develop a more efficient anti-aging MNP product, we fabricated a dual anti-wrinkle microneedle patch (named DA-MNP) using droplet extension (DEN®) technology and evaluated its skin puncture ability, safety, and efficacy through clinical studies. METHODS: A DA-MNP comprising hyaluronic acid (HA) polymer backbone, acetyl octapeptide-3, and L-ascorbic acid 2-glucoside and sodium cyclic lysophosphatidic acid was fabricated using DEN® technology. Placebo MNPs comprising only HA were also fabricated. Twenty-four healthy subjects were enrolled in this comparative clinical study. The DA-MNP or placebo MNP was separately applied to the left and right eyes of subjects for overnight. Assessments, including wrinkle improvement, trans-epidermal water loss (TEWL), eye lifting and adverse effects were evaluated at each scheduled visit day for 28 days. RESULTS: The DA-MNP showed mechanical strength enough for puncturing the stratum corneum. Compared to placebo MNP group, the DA-MNP treated group showed an effective eye wrinkles improvement and better anti-aging of skin, with reduced TEWL, enhanced skin elasticity and lifting, and no adverse effects. CONCLUSION: The present study demonstrated that the fabricated DA-MNP exhibited fast acting on deep wrinkles and enhanced anti-aging efficacy, with no skin safety concern. Thus, this DA-MNP may serve as a new transdermal delivery solution for skin wrinkling and aging.

Current strategies using 3D organoids to establish in vitro maternal-embryonic interaction.

IMPORTANCE: The creation of robust maternal-embryonic interactions and implantation models is important for comprehending the early stages of embryonic development and reproductive disorders. Traditional two-dimensional (2D) cell culture systems often fail to accurately mimic the highly complex in vivo conditions. The employment of three-dimensional (3D) organoids has emerged as a promising strategy to overcome these limitations in recent years. The advancements in the field of organoid technology have opened new avenues for studying the physiology and diseases affecting female reproductive tract. OBSERVATIONS: This review summarizes the current strategies and advancements in the field of 3D organoids to establish maternal-embryonic interaction and implantation models for use in research and personalized medicine in assisted reproductive technology. The concepts of endometrial organoids, menstrual blood flow organoids, placental trophoblast organoids, stem cell-derived blastoids, and in vitro-generated embryo models are discussed in detail. We show the incorportaion of organoid systems and microfluidic technology to enhance tissue performance and precise management of the cellular surroundings. CONCLUSIONS AND RELEVANCE: This review provides insights into the future direction of modeling maternal-embryonic interaction research and its combination with other powerful technologies to interfere with this dialogue either by promoting or hindering it for improving fertility or methods for contraception, respectively. The merging of organoid systems with microfluidics facilitates the creation of sophisticated and functional organoid models, enhancing insights into organ development, disease mechanisms, and personalized medical investigations.

Comparison between the mesenteric fixation method (MEFIX) and conventional methods at preventing the occurrence of Petersen's hernia: a study protocol for a multicenter randomized controlled trial.

BACKGROUND: Petersen's hernia, which occurs after Billroth-II (B-II) or Roux-en-Y (REY) anastomosis, can be reduced by defect closure. This study aims to compare the incidence of bowel obstruction above Clavien-Dindo classification grade III due to Petersen's hernia between the mesenteric fixation method and the conventional methods after laparoscopic or robotic gastrectomy. METHODS: This study was designed as prospective, single-blind, non-inferiority randomized controlled multicenter trial in Korea. Patients with histologically diagnosed gastric cancer of clinical stages I, II, or III who underwent B-II or REY anastomosis after laparoscopic or robotic gastrectomy are enrolled in this study. Participants who meet the inclusion criteria are randomly assigned to two groups: a CLOSURE group that underwent conventional Petersen's defect closure method and a MEFIX group that underwent the mesenteric fixation method. The primary endpoint is the number of patients who underwent surgery for bowel obstruction caused by Petersen's hernia within 3 years after laparoscopic or robotic gastrectomy. DISCUSSION: This trial is expected to provide high-level evidence showing that the MEFIX method can quickly and easily close Petersen's defect without increased postoperative complications compared to the conventional method. TRIAL REGISTRATION: ClinicalTrials.gov NCT05105360. Registered on November 3, 2021.

Nanostar and nanonetwork crystals fabricated by in situ nanoparticlization of fully conjugated polythiophene diblock copolymers.

Nanostar and nanonetwork crystals were prepared from fully conjugated poly(3-(2-ethylhexyl)thiophene)-block-polythiophene (P3EHT-b-PT) via a simple INCP process. The structural conformation of the nanocrystals was investigated in detail, revealing that with an increase in the block length of PT, the morphology of the nanocrystals changed from nanospheres to nanorods, nanostars, and to nanonetworks.

One-pot in situ fabrication of stable nanocaterpillars directly from polyacetylene diblock copolymers synthesized by mild ring-opening metathesis polymerization.

We report a direct one-pot route for the preparation of supramolecules from simple polyacetylene diblock copolymers synthesized by mild ring-opening metathesis polymerization of cyclooctatetraene. This in situ nanoparticlization of conjugated polymer (INCP) approach is advantageous over conventional self-assembly processes because this method does not require any tedious postsynthetic treatments. Also, this direct approach provides intriguing supramolecules with a unique nanostructure resembling a caterpillar. Furthermore, the new supramolecules are highly stable adducts because the polyacetylene core block provides an exceptionally strong driving force for the self-assembly. Even though pristine polyacetylene is unstable in air, the polyacetylene segment in the nanocaterpillar is very stable because it is protected within the shell of the supramolecule.

A case of metastatic leptomeningeal carcinomatosis from early gastric carcinoma.

Metastatic leptomeningeal carcinomatosis is estimated to occur in 3% to 8% of solid carcinomas. The most common causes of leptomeningeal carcinomatosis are breast cancer, lung cancer and malignant melanoma. Leptomeningeal carcinomatosis associated with gastric cancer, especially in its early stages, is exceedingly rare. Its presenting symptoms include headache, nausea and seizures. In this report, we describe a case of leptomeningeal metastasis that presented with early-stage gastric cancer. A 67-year-old woman with a history of early-stage gastric cancer in remission was admitted to our hospital with 3 days of headache and nausea. Her gastric cancer had been treated 29 months prior to presentation by a radical subtotal gastrectomy with a Billroth I anastomosis. She had an uneventful recovery until she was diagnosed with metastases to the left axilla and neck 26 months after surgery. Her presenting symptoms of headache and nausea prompted cytologic examination of the cerebrospinal fluid and measurement of tumor markers, which revealed metastatic leptomeningeal carcinomatosis from her gastric cancer. This report aims to raise awareness of the possibility that even early-stage gastric cancer can lead to leptomeningeal carcinomatosis.

Scalable and continuous access to pure cyclic polymers enabled by 'quarantined' heterogeneous catalysts.

Cyclic polymers are topologically interesting and envisioned as a lubricant material. However, scalable synthesis of pure cyclic polymers remains elusive. The most straightforward way is to recover a used catalyst after the synthesis of cyclic polymers and reuse it. Unfortunately, this is demanding because of the catalyst's vulnerability and inseparability from polymers, which reduce the practicality of the process. Here we develop a continuous circular process, where polymerization, polymer separation and catalyst recovery happen in situ, to dispense a pure cyclic polymer after bulk ring-expansion metathesis polymerization of cyclopentene. It is enabled by introducing silica-supported ruthenium catalysts and newly designed glassware. Different depolymerization kinetics of the cyclic polymer from its linear analogue are also discussed. This process minimizes manual labour, maximizes the security of vulnerable catalysts and guarantees the purity of cyclic polymers, thereby showcasing a prototype of a scalable access to cyclic polymers with increased turnovers (≥415,000) of precious catalysts.

Prediction of the possibility of laparoscopic reduction of Petersen's hernia after gastrectomy: multicenter observational cohort study.

INTRODUCTION: Petersen's hernia (PH) is a potentially fatal complication of bowel infarction that is difficult to treat by laparoscopic reduction. AIM: To define predictive computed tomography (CT) profiles to identify PH patients who would be suitable for laparoscopic reduction by a comparative analysis between patients treated by laparoscopic and open reduction. MATERIAL AND METHODS: We retrospectively collected the clinical data of patients (n = 28) who underwent PH reduction surgery after minimally invasive gastrectomy for gastric cancer in the period 2015-2018 at four training hospitals. We examined the preoperative CT scans to identify the indications for laparoscopic PH reduction. RESULTS: We compared the laparoscopic reduction group (laparoscopic group, n = 15) and the open reduction group (open group, n = 13). Patients in the laparoscopic group were younger (55.7 ±10.4) than those in the open group (69.3 ±9.1), but there were no differences in clinical or laboratory findings. We found that there were two CT profiles with significant differences between the open and laparoscopic groups: superior mesenteric vein (SMV) narrowing and small bowel dilation. We found that small bowel dilatation was an independent factor on multivariate analysis for laparoscopic PH reduction. CONCLUSIONS: We found that small bowel dilatation is the most important CT profile for identifying PH patients contraindicated for laparoscopic reduction. Despite the retrospective design of this study, these CT profiles are expected to define the scope of laparoscopic reduction in PH patients and to establish indications for the laparoscopic approach.

Sulfenamide-enabled ortho thiolation of aryl iodides via palladium/norbornene cooperative catalysis.

Poly-substituted aromatic sulfur compounds are widely found in pharmaceuticals, agrochemicals and organic materials. However, the position that a sulfur moiety can be introduced to is largely restricted to a pre-functionalized site; otherwise, use of electronically biased substrates or auxiliary groups that direct catalysis is required. Here we report a general ortho thiolation of common aryl and heteroaryl iodides via palladium-norbornene cooperative catalysis. Using this approach, an aryl or alky sulfur moiety can be site-selectively introduced at the arene ortho position without using sterically or electronically biased substrates. The arene ipso functionalization is simultaneously achieved through Heck, Suzuki or Sonogashira termination. The reaction is enabled by a unique class of electrophiles in palladium-norbornene cooperative catalysis, which are sulfenamides derived from seven-membered lactams. The broad substrates scope and high chemoselectivity could make this method attractive for synthesis of complex sulfur-containing aromatic compounds.

Size distributions of total airborne particles and bioaerosols in a municipal composting facility.

Size distributions of total airborne particles and bioaerosols were measured in a full-scale composting facility, using an optical particle counter and an agar-inserted six-stage impactor, respectively. Higher concentrations of total airborne particles and bioaerosols were detected at a sampling location near the screening process preceded by the composting process than at sampling locations in the composting process. At the sampling location near the screening process, the concentrations of total airborne particles were approximately 10(8)particles/m3 at the size of 0.3 microm and 10(5)particles/m3 at 6.2 microm. The concentration of bioaerosols was about 10(4)CFU/m3 in each stage of 7.0 microm (1st stage), 7.0-4.7 microm (2nd), 4.7-3.3 microm (3rd), 3.3-2.1 microm (4th), 2.1-1.1 microm (5th) and 1.1-0.65 microm (6th). Most of submicron particles smaller than 1 microm among the total airborne particles were believed to originate from the ambient air.

A modular synthetic approach for band-gap engineering of armchair graphene nanoribbons.

Despite the great promise of armchair graphene nanoribbons (aGNRs) as high-performance semiconductors, practical band-gap engineering of aGNRs remains an unmet challenge. Given that width and edge structures are the two key factors for modulating band-gaps of aGNRs, a reliable synthetic method that allows control of both factors would be highly desirable. Here we report a simple modular strategy for efficient preparation of N = 6 aGNR, the narrowest member in the N = 3p (p: natural number) aGNR family, and two unsymmetrically edge-functionalized GNRs that contain benzothiadiazole and benzotriazole moieties. The trend of band-gap transitions among these GNRs parallels those in donor-acceptor alternating conjugated polymers. In addition, post-functionalization of the unsymmetrical heterocyclic edge via C-H borylation permits further band-gap tuning. Therefore, this method opens the door for convenient band-gap engineering of aGNRs through modifying the heteroarenes on the edge.