From the Cover: Emergence of dynamic vortex glasses in disordered polar active fluids

In equilibrium, disorder conspires with topological defects to redefine the ordered states of matter in systems as diverse as crystals, superconductors, and liquid crystals. Far from equilibrium, however, the consequences of quenched disorder on active condensed matter remain virtually uncharted. Here, we reveal a state of strongly disordered active matter with no counterparts in equilibrium: a dynamical vortex glass. Combining microfluidic experiments and theory, we show how colloidal flocks collectively cruise through disordered environments without relaxing the topological singularities of their flows. The resulting state is highly dynamical but the flow patterns, shaped by a finite density of frozen vortices, are stationary and exponentially degenerated. Quenched isotropic disorder acts as a random gauge field turning active liquids into dynamical vortex glasses. We argue that this robust mechanism should shape the collective dynamics of a broad class of disordered active matter, from synthetic active nematics to collections of living cells exploring heterogeneous media.

From a physicist’s perspective, flocks are ensembles of living or synthetic motile units collectively moving along a common emerging direction (1–4). They realize one of the most robust ordered states of matter observed over five orders of magnitude in scale and in systems as diverse as motility assays, self-propelled colloids, shaken grains, and actual flocks of birds (3, 5–10). The quiet flows of flocks are in stark contrast with the spatiotemporal chaos consistently reported and predicted in active nematic liquid crystals, another abundant form of ordered active matter realized in biological tissues, swimming cells, cellular extracts, and shaken rods (2, 11). Active nematics do not support any form of long-range order (4, 12). Their structure is continuously bent and destroyed by the proliferation and annihilation of singularities in their local orientation: topological defects (11, 13–15). Unlike in active nematics, topological defects in flocking matter are merely transient excitations which annihilate rapidly and allow uniaxial order to extend over system-spanning scales (4).This idyllic view of the ordered phases of active liquids is limited, however, to pure systems. Disorder is known to profoundly alter the stability of topological defects and the corresponding ordered states in equilibrium condensed matter (16–18), but its role in active fluids remains virtually uncharted territory. All previous studies (19–26), including our own early experiments (22), have been limited to weak disorder and smooth perturbations around topologically trivial states. Unlike in equilibrium, no available experiment, simulation, or theory has ever demonstrated or predicted disorder-induced topological excitations in active matter.In this paper we show how isotropic disorder generically challenges the extreme robustness of flocking matter to topological defects. We map the full phase behavior of colloidal flocks navigating through disordered lattice of obstacles and reveal an unanticipated state of active matter: a dynamical vortex glass. In dynamical vortex glasses, millions of self-propelled particles can steadily cruise through disorder, maintaining local orientational order and without relaxing the topological singularities of their flows. The associated flow patterns are exponentially degenerated and shaped by amorphous ensembles of frozen topological defects, yielding a dynamical state akin to the static vortex-glass phase of dirty superconductors and random-gauge magnets (27–29). Building a theory of flock hydrodynamics beyond the spin-wave approximation, we elucidate the emergence and stabilization of topological vortices by quenched disorder. Finally, we discuss the universality of the dynamical vortex glass phase beyond the specifics of polar active matter and colloidal flocks.     

The Wear on Roller Press Rollers Made of 20Cr4/1.7027 Steel under Conditions of Copper Concentrate Briquetting

This paper defines the wear process of rollers made of 20Cr4. Rollers with a diameter of 1000 mm were installed in a roller press used for the production of drop-shaped briquettes and the copper concentrate was briquetted for 1100 h. Three-dimensional (3D) geometry analysis, metallographic analysis, macroscopy, scanning electron microscopy, as well as hardness measurements were performed. It was observed that the working surface was non-uniformly worn. The smallest wear affects the molding cavities situated on the outermost edges of the ring. The wear increases as the center of the ring is approximated, and it reaches its maximum at the middle of the ring. The molding cavities also wear asymmetrically. For the shape considered in this study, the lower part of a cavity is subject to a higher wear rate. We found that the material of the working ring was carburized, but its hardness was significantly lower than required. The roller ring microstructure changes depended on the distance from the cavity’s face. An investigation of the wear mechanisms showed different types of abrasive wear, corrosive processes, and plastic deformation. The exact type and course of wear were described, depending on the location on the working surface.     

高频微针电灼仪治疗24例中重度腋臭患者临床研究

目的 评价使用高频微针电灼仪治疗腋臭的安全性及有效性.方法 收集2015年6月至2016年6月,北京协和医院皮肤科就诊的中重度腋臭患者24例,使用高频微针电灼仪(BodyTiteTM)进行单次治疗,治疗前后使用视觉-气味计分量表(VAS)评价腋下气味,生活质量SF-36量表评估健康相关生活质量,取患者腋下皮肤组织行病理学活检.结果 VAS量表评估显示,24例中22例达到并维持≥12周的症状缓解,平均气味评分下降率(VAS％)50％ ～ 100％,1例治疗后12周腋臭复发,1例未获得临床缓解.SF-36量表评估显示,治疗前患者在社会功能、情感职能、精神健康领域得分[M(P0～P100)]分别为77.50(62.50～100.00)、66.67(33.30 ～ 100.00)、55.00(48.88 ～ 72.00),治疗后分别升至100.00(62.00 ～ 112.50)、100.00(33.30 ～ 110.00)、68.00 (48.00～ 80.00),治疗前后差异有统计学意义(均P＜ 0.05).组织病理显示,治疗后22例汗腺导管细胞出现明显变性、坏死,2例出现表皮损伤.安全性方面,1例治疗后出现单侧上肢疼痛,2例出现小面积皮肤烫伤样改变.术后平均恢复时间为7～ 14d.结论 高频微针电灼仪治疗腋臭临床有效率高,有良好的安全性,具有临床应用前景.     

Measles vaccination using a microneedle patch

Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1 log₁₀(TCID₅₀) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection.     

微针联合硬化剂对鸡冠毛细血管网作用的实验研究

目的探讨微针联合不同种类硬化剂对浅表血管性病变作用的特点。方法选择1．5～2．0kg雄性莱航鸡30只作为研究对象。随机分成3组：A组微针＋聚桂醇，B组微针＋无水乙醇，以及C组正常鸡冠，每组均为10只。分别在微针联合硬化剂干预鸡冠后第7、14、21、28天切取鸡冠组织，进行HE染色和免疫组化染色，分别计算毛细血管数目及Ⅰ型、Ⅲ型胶原纤维面积。结果肉眼观察：鸡冠组织颜色随时间的推移而变浅；HE染色显示：两实验组鸡冠组织毛细血管数目均明显随时间的延长而减少，且A组减少更明显；Ⅰ型胶原纤维及Ⅲ型胶原纤维面积计算结果显示：A、B、C组各时段组间对比，差异无统计学意义（P〉0．05）。结论动物实验结果显示，微针联合两种硬化剂均可显著减少鸡冠组织的毛细血管数量，最终导致鸡冠颜色变浅，其中以微针＋聚桂醇效果更明显；Ⅰ型、Ⅲ型胶原纤维未见增生，所以微针联合硬化剂干预鸡冠组织后不会导致局部纤维化。     

Delivery of salmon calcitonin using a microneedle patch

Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL min). T_max (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.     

Safety and efficacy of a novel microneedle device for dose sparing intradermal influenza vaccination in healthy adults

Background

Intradermal vaccine delivery has been shown to induce good immune responses with low vaccine doses. Technologies for drug-delivery which specifically target the skin may render intradermal vaccination more accessible.

Methods

We conducted a prospective, randomized trial in 180 intended-to-treat healthy adults. Study objectives were to evaluate the safety and immunogenicity of low-dose intradermal (ID) influenza vaccines delivered using a novel microneedle device (MicronJet). This device replaces a conventional needle, and is designed specifically for intradermal delivery.Subjects were randomly assigned to receive either the full-dose standard flu shot (containing 15 μg hemagglutinin per strain) delivered intramuscularly using a conventional needle (IM group), a medium dose intradermal injection (6 μg hemagglutinin per strain) delivered with the MicronJet (ID2 group), or a low-dose intradermal injection (3 μg hemagglutinin per strain) delivered with the MicronJet (ID1 group). A marketed influenza vaccine for the 2006/2007 influenza season (α-RIX^® by GSK Biologicals) was used for all injections.Adverse events were recorded over a 42-day period. Immunogenicity was evaluated by changes in hemagglutination inhibition (HAI) antibody titer, and by comparing geometric mean titers (GMTs), seroconversion, and seroprotection rates between the study groups.

Results

Local reactions were significantly more frequent following intradermal vaccination, but were mild and transient in nature. At 21 days after injection, GMT fold increase was 22, 18 and 22 in the ID1, ID2 and IM groups respectively for the H1N1 strain; 9, 9 and 16 for the H3N2 strain and 9, 13 and 11 for strain B. The CPMP criteria for re-licensure of seasonal influenza vaccines were met in full for all study groups.

Conclusions

Low-dose influenza vaccines delivered intradermally using microneedles elicited immunogenic responses similar to those elicited by the full-dose intramuscular vaccination. The microneedle injection device used in this study was found to be effective, safe, and reliable.     

绷带卷加压包扎预防起搏器植入术后囊袋出血的应用效果

目的 探讨绷带卷加压包扎在永久心脏起搏器植入术后囊袋止血中的应用效果.方法 选取永久心脏起搏器植入患者591例,分为试验组和对照组.试验组(296例)用两个医用绷带卷并排放置于起搏器囊袋上方,与切口平行,3M胶布条固定绷带卷,松紧以伤口不出血、绷带卷无移位为准,术后6 h松解胶布条和绷带卷.对照组(295例)将1 000 g沙袋置于起搏器囊袋上方,术后6 h取走沙袋.比较两组患者压迫止血的安全性和有效性.结果 两组在切口出血、囊袋血肿和皮肤压力性损伤发生方面比较差异无统计学意义(P>0.05);试验组切口疼痛、尿潴留和睡眠障碍的发生率低于对照组,比较差异有统计学意义(P<0.05).结论 绷带卷加压包扎法可明显减少患者伤口疼痛、尿潴留、睡眠障碍的发生.     

聚左旋乳酸微针导入改善肤质的效果研究

为分析聚左旋乳酸微针导入对肤质的改善效果,本研究选取2022年1月-6月于我院行肤质改善 干预的12例患者为研究对象,使用聚左旋乳酸微针进行干预。结果显示,接受面部肤质改善的6例患者治 疗后面部肤质的整体改善效果较好,提亮效果十分理想,治疗后棕色斑区域评分为（76.58±23.71）分,低于 治疗前的（110.21±24.36）分,差异有统计学意义（P＜0.05）;接受手部肤质干预的2例患者肤质为C级轻微 改善,其手部褶皱以及细纹明显减少;接受颈部肤质干预的4例患者肤质改善效果也十分理想。可见,使 用聚左旋乳酸微针来对面部、颈部以及手部等肤质进行干预,不仅有良好的肤质改善效果,还具有一定安 全性,应用效果理想。     

Intradermal delivery of a quadrivalent cell-based seasonal influenza vaccine using an adjuvanted skin patch vaccination platform

All seasonal influenza vaccines for 2021–2022 in the US were quadrivalent and the market continues to be dominated by intramuscular delivery of non-adjuvanted, virion-derived antigens grown in chicken eggs. Up to four new egg-adapted production influenza vaccine strains must be generated each year. The introduction in 2012 of Flucelvax®, which is grown in mammalian suspension cell culture and uses vaccine production strains without adaptive mutations for efficient growth in eggs, represented a major advance in vaccine production technology. Here we demonstrate that Flucelvax can be reformulated and combined with a liposomal adjuvant containing QS-21 (Verndari Adjuvant System 1.1, VAS1.1) or QS-21 and 3D-PHAD (VAS1.2) for intradermal administration using a painless skin patch, VaxiPatch?. VAS1.2 is similar to AS01_B, the adjuvant system used in Shingrix® and Mosquirix?. We show that Flucelvax, when reformulated and concentrated using tangential flow filtration (TFF), maintains hemagglutination and single radial immunodiffusion (SRID) potency. Loading the reformulated Flucelvax material onto VaxiPatch arrays conferred high levels of resistance to heat stress and room temperature stability. TFF enriched vaccine antigens were combined with VAS1.1 or VAS1.2 and dispensed in 10nL drops into the pockets of 36 (total 360 nL) stainless steel microneedles arranged in a microarray 1.2 cm in diameter. Using VaxiPatch delivery of 2 µg of antigen, we demonstrated intramusuclar-comparable IgG and hemagglutination inhibition (HAI) immune responses in Sprague Dawley® rats. With addition of VAS1.2, antigen-specific IgG titers were increased as much as 68-fold (47-fold for VAS1.1) with improvements in seroconversion for three of four strains (all four were improved by VAS1.1). TFF-reformulated antigens combined with VAS1.1 or VAS1.2 and delivered by VaxiPatch showed only minor skin reactogenicity after 1 h and no skin reactogenicity after 24 h. These data indicate that VaxiPatch and the VAS system have the potential to be transformative for vaccine delivery.