Making Topologically Trivial Non-Hermitian Systems Nontrivial via Gauge Fields.

Non-Hermiticity significantly enriches the concepts of symmetry and topology in physics. Particularly, non-Hermiticity gives rise to the ramified symmetries, where the non-Hermitian Hamiltonian H is transformed to H^{†}. For time-reversal (T) and sublattice symmetries, there are six ramified symmetry classes leading to novel topological classifications with various non-Hermitian skin effects. As artificial crystals are the main experimental platforms for non-Hermitian physics, there exists the symmetry barrier for realizing topological physics in the six ramified symmetry classes: while artificial crystals are in spinless classes with T^{2}=1, nontrivial classifications dominantly appear in spinful classes with T^{2}=-1. Here, we present a general mechanism to cross the symmetry barrier. With an internal parity symmetry P, the square of the combination T[over ˜]=PT can be modified by appropriate gauge fluxes. Using the general mechanism, we systematically construct spinless models for all non-Hermitian spinful topological phases in one and two dimensions, which are experimentally realizable. Our Letter suggests that gauge structures may significantly enrich non-Hermitian physics at the fundamental level.

Non-Hermitian Spatial Symmetries and Their Stabilized Normal and Exceptional Topological Semimetals.

We study non-Hermitian spatial symmetries-a class of symmetries that have no counterparts in Hermitian systems-and study how normal and exceptional semimetals can be stabilized by these symmetries. Different from internal ones, spatial symmetries act nonlocally in momentum space and enforce global constraints on both band degeneracies and topological quantities at different locations. In deriving general constraints on band degeneracies and topological invariants, we demonstrate that non-Hermitian spatial symmetries are on an equal footing with, but are essentially different from Hermitian ones. First, we discover the nonlocal Hermitian conjugate pair of exceptional or normal band degeneracies that are enforced by non-Hermitian spatial symmetries. Remarkably, we find that these pairs lead to the symmetry-enforced violation of the Fermion doubling theorem in the long-time limit. Second, with the topological constraints, we unravel that a certain exceptional manifold is only compatible with and stabilized by non-Hermitian spatial symmetries but is intrinsically incompatible with Hermitian spatial symmetries. We illustrate these findings using two three-dimensional models of a non-Hermitian Weyl semimetal and an exceptional unconventional Weyl semimetal. Experimental cold-atom realizations of both models are also proposed.

"After viral load testing, I get my results so I get to know which path my life is taking me": qualitative insights on routine centralized and point-of-care viral load testing in western Kenya from the Opt4Kids and Opt4Mamas studies.

BACKGROUND: Viral suppression (VS) is a marker of effective HIV therapy, and viral load (VL) testing is critical for treatment monitoring, especially in high-risk groups such as children and pregnant/postpartum women. Although routine VL testing, via centralized laboratory networks, was implemented in Kenya starting in 2014, optimization and sustainable scale up of VL testing are still needed. METHODS: We conducted a mixed methods study to evaluate the impact of higher frequency, point-of-care (POC) VL testing in optimizing VS among children and pregnant/postpartum women on antiretroviral treatment (ART) in five HIV treatment facilities in western Kenya in the Opt4Kids and Opt4Mamas studies. We conducted 68 key informant interviews (KIIs) from December 2019 to December 2020 with children and pregnant women living with HIV, child caregivers, providers, laboratory/facility leadership, and county- or national-level policymakers. Our KII guide covered the following domains: (1) barriers and facilitators to ART use and VS, (2) literacy and experiences with VL in routine care and via study, and (3) opinions on how to scale up VL testing for optimal programmatic use. We used inductive coding and thematic analysis to identify dominant themes with convergent and divergent subthemes. RESULTS: Three main themes regarding VL testing emerged from our analysis. (1) Key informants uniformly contrasted POC VL testing's faster results turnaround, higher accessibility, and likely cost-effectiveness against centralized VL testing. (2) Key informants also identified areas of improvement for POC VL testing in Kenya, such as quality control, human resource and infrastructure capacity, supply chain management, and integration of VL testing systems. (3) To enable successful scale-up of VL testing, key informants proposed expanding the POC VL testing scheme, electronic medical records systems, conducting quality checks locally, capacity building and developing strong partnerships between key stakeholders. CONCLUSION: The more accessible, decentralized model of POC VL testing was deemed capable of overcoming critical challenges associated with centralized VL testing and was considered highly desirable for optimizing VS for children and pregnant/postpartum women living with HIV. While POC VL testing has the potential to improve VS rates among these populations, additional research is needed to develop strategies for ensuring the sustainability of POC VL testing programs. TRIAL REGISTRATION: NCT03820323, 29/01/2019.

Arthroscopic Hip Capsular Reconstruction Using Iliotibial Band Allograft as a Salvage Option for Unrepairable Capsular Defects Demonstrates Good Survivorship and Improved Patient-Reported Outcomes.

PURPOSE: To describe patient outcomes 3 to 5 years after arthroscopic hip capsule reconstruction. METHODS: Between January 2007 and December 2016, patients aged 18 to 50 years who underwent arthroscopic hip capsular reconstruction using an Iliotibial band allograft by the senior author and had minimum of 3-year follow-up were identified. Patients were excluded if they had previous open hip surgery, advanced osteoarthritis (Tönnis grade >2), significant acetabular dysplasia (lateral center edge angle <20°), avascular necrosis, or Legg-Calve-Perthes disease. Outcome scores including the Hip Outcome Score (HOS)-Activities of Daily Living scale, modified Harris Hip Score, HOS-Sports scale, SF-12, and Western Ontario & McMaster Universities Osteoarthritis Index were compared in addition to failure rate, revision rate, and patient satisfaction rate with the outcome (range, 1-10). All patients were assessed by the senior author pre- and postoperatively. RESULTS: Thirty-nine patients met the inclusion criteria. The mean age of the cohort was 32 ± 10 years, with 6 male and 33 female patients. The average number of previous hip arthroscopy surgeries was 2 ± 1. Six patients (15%) converted to total hip arthroplasty at an average of 2.1 years (range 7 months to 6 years) following capsular reconstruction. Four patients required revision hip arthroscopy after the arthroscopic capsular reconstruction. All arthroscopic revisions occurred in female patients with the primary intraoperative finding of capsulolabral adhesions at the time of revision. At mean follow-up of 4.3 years (range 3-6.8 years), the 29 patients who did not require subsequent surgery had significant improvements from preoperatively to postoperatively in HOS-Activities of Daily Living and HOS-Sport with 90% reaching minimal clinically important difference. All other scores showed significant improvement. Survival for patients not requiring total hip arthroplasty was 86% at 3 years, with a mean survival of 5.7 years (95% confidence interval 4.97-6.4). CONCLUSIONS: Arthroscopic hip capsular reconstruction with iliotibial band allograft is a successful treatment option for patients with symptomatic capsular defects, demonstrating improved patient-reported outcomes maintained at mean follow-up time of 4 years. This technique offers restoration of the anatomic structure and function of the capsular ligaments to improve pain and instability. LEVEL OF EVIDENCE: IV, case series.

Catalytic Performance of Immobilized Sulfuric Acid on Silica Gel for N-Formylation of Amines with Triethyl Orthoformate.

In the search for convenient, green, and practical catalytic methods for the current interest in organic synthesis, a simple, green, and highly efficient protocol for N-formylation of various amines was carried out in the presence of immobilized sulfuric acid on silica gel (H2SO4-SiO2). All reactions were performed in refluxing triethyl orthoformate (65 °C). The product formamides were obtained with high-to-excellent yields within 4 min to 2 h. The current approach is advantageous, due to its short reaction time and high yields. The catalyst is recyclable with no significant loss in catalytic efficiency.

Unlocking the Diversity of Pyrroloiminoquinones Produced by Latrunculid Sponge Species.

Sponges of the Latrunculiidae family produce bioactive pyrroloiminoquinone alkaloids including makaluvamines, discorhabdins, and tsitsikammamines. The aim of this study was to use LC-ESI-MS/MS-driven molecular networking to characterize the pyrroloiminoquinone secondary metabolites produced by six latrunculid species. These are Tsitsikamma favus, Tsitsikamma pedunculata, Cyclacanthia bellae, and Latrunculia apicalis as well as the recently discovered species, Tsitsikamma nguni and Tsitsikamma michaeli. Organic extracts of 43 sponges were analyzed, revealing distinct species-specific chemical profiles. More than 200 known and unknown putative pyrroloiminoquinones and related compounds were detected, including unprecedented makaluvamine-discorhabdin adducts and hydroxylated discorhabdin I derivatives. The chemical profiles of the new species T. nguni closely resembled those of the known T. favus (chemotype I), but with a higher abundance of tsitsikammamines vs. discorhabdins. T. michaeli sponges displayed two distinct chemical profiles, either producing mostly the same discorhabdins as T. favus (chemotype I) or non- or monobrominated, hydroxylated discorhabdins. C. bellae and L. apicalis produced similar pyrroloiminoquinone chemistry to one another, characterized by sulfur-containing discorhabdins and related adducts and oligomers. This study highlights the variability of pyrroloiminoquinone production by latrunculid species, identifies novel isolation targets, and offers fundamental insights into the collision-induced dissociation of pyrroloiminoquinones.

Euphorbia Diterpenes: An Update of Isolation, Structure, Pharmacological Activities and Structure-Activity Relationship.

Euphorbia species have a rich history of ethnomedicinal use and ethnopharmacological applications in drug discovery. This is due to the presence of a wide range of diterpenes exhibiting great structural diversity and pharmacological activities. As a result, Euphorbia diterpenes have remained the focus of drug discovery investigations from natural products. The current review documents over 350 diterpenes, isolated from Euphorbia species, their structures, classification, biosynthetic pathways, and their structure-activity relationships for the period covering 2013-2020. Among the isolated diterpenes, over 20 skeletal structures were identified. Lathyrane, jatrophane, ingenane, ingenol, and ingol were identified as the major diterpenes in most Euphorbia species. Most of the isolated diterpenes were evaluated for their cytotoxicity activities, multidrug resistance abilities, and inhibitory activities in vitro, and reported good activities with significant half-inhibitory concentration (IC50) values ranging from 10-50 µM. The lathyranes, isopimaranes, and jatrophanes diterpenes were further found to show potent inhibition of P-glycoprotein, which is known to confer drug resistance abilities in cells leading to decreased cytotoxic effects. Structure-activity relationship (SAR) studies revealed the significance of a free hydroxyl group at position C-3 in enhancing the anticancer and anti-inflammatory activities and the negative effect it has in position C-2. Esterification of this functionality, in selected diterpenes, was found to enhance these activities. Thus, Euphorbia diterpenes offer a valuable source of lead compounds that could be investigated further as potential candidates for drug discovery.

Review of the Traditional Uses, Phytochemistry, and Pharmacological Activities of Rhoicissus Species (Vitaceae).

Species within the genus Rhoicissus (Vitaceae) are commonly used in South African traditional medicine. The current review discusses the occurrence, distribution, traditional uses, phytochemistry, and pharmacological properties of Rhoicissus species covering the period 1981-2020. The data reported were systematically collected, read, and analysed from scientific electronic databases including Scopus, Scifinder, Pubmed, and Google Scholar. Reported evidence indicates that species in this genus are used for the treatment of gastrointestinal complaints, sexually transmitted infections (STIs), and infertility, as well as to tone the uterus during pregnancy and to facilitate delivery. Pharmacological studies have further shown that members of the Rhoicissus genus display antidiabetic, uterotonic, ascaricidal, hepatoprotective, antioxidant, antimicrobial, anticancer, and anti-inflammatory properties. They are linked to the presence of bioactive compounds isolated from the genus. Hence, Rhoicissus species can potentially be an alternative therapeutic strategy to treat diseases and develop safer and more potent drugs to combat diseases. Plant species of this genus have valuable medicinal benefits due to their significant pharmacological potential. However, scientific investigation and information of the therapeutic potential of Rhoicissus remain limited as most of the species in the genus have not been fully exploited. Therefore, there is a need for further investigations to exploit the therapeutic potential of the genus Rhoicissus. Future studies should evaluate the phytochemical, pharmacological, and toxicological activities, as well as the mode of action, of Rhoicissus crude extracts and secondary compounds isolated from the species.

[A study of LEF1 protein expression in diagnosis and differential diagnosis of lymphoblastic lymphoma/acute lymphoblastic leukemia].

Objective: To evaluate the expression of LEF1 protein in lymphoblastic lymphoma/acute lymphoblastic leukemia (LBL/ALL) and small B-cell lymphomas, and its value in pathologic diagnosis and differential diagnosis of LBL/ALL. Methods: 53 cases of LBL/ALL were collected at shanghai Tongji Hospital from January 2012 to December 2019. The protein expression of LEF1 and TdT was detected by immunohistochemistry in 53 paraffin-embedded tissue samples of LBL/ALL. The specificity and sensitivity of LEF1 and TdT in the diagnosis of LBL/ALL were compared. The expression of LEF1 protein in 77 cases of small B-cell lymphomas including chronic lymphocytic leukemia/small lymphoid lymphoma (CLL/SLL), follicular lymphoma, mantle cell lymphoma, marginal zone lymphoma and Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma was studied. The correlation between LEF1 expression and overall survival (OS) and progression-free survival (PFS) was performed by univariate analysis. Results: The expression of LEF1 in LBL/ALL was 100% (53/53), the median value was 90%; the expression of TdT was 84.9% (T-LBL/ALL 78.1%, B-LBL/ALL 95.2%), the median value was 80%; the expression rate and median value of LEF1 and TdT were significantly different (P=0.008 and 0.001 respectively). The expression of LEF1 in CLL/SLL was 14/18, the median value was 45%; LEF1 was not expressed in follicular lymphoma (0/16), mantle cell lymphoma (0/16), marginal zone lymphoma (0/19), and Waldenstrom's macroglobulinemia/lymphoplasmacytic lymphoma (0/8). LEF1 expression was significantly different between B-LBL/ALL and small B-cell lymphomas. The median follow-up time of LBL/ALL cases in this group was 16 months. There was no statistical difference between LEF1 expression and the OS and PFS in LBL/ALL patients. Conclusions: Immunohistochemical staining of LEF1 has high sensitivity and good specificity in the diagnosis of LBL/ALL, and its combination with TdT can improve the diagnostic rate of LBL/ALL.

Synthesis and biological evaluation of bis-N2,N2'-(4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccinodihydrazides.

A series of N2,N2'-bis[4-hydroxycoumarin-3-yl)ethylidene]-2,3-dihydroxysuccino-hydrazides, containing 4-hydroxycoumarin, hydrazine and tartaric acid moieties, have been prepared and examined for possible biological activity. Several of these compounds exhibit promising HIV-1 integrase inhibition (IC50 = 3.5 µM), and anti-T. brucei (32% viability) and anti-mycobacterial (Visual MIC90 = 15.63 µM) activity.